Clinical trial NCT04678440
Conditions: Lung Cancer, Nonsmall Cell
Keywords: total body positron emission tomography
Sponsor: University of California, Davis
Start date: 2021-03-31; Completion date: 2023-02-07
Enrollment: 5 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
In this pilot study, healthy volunteers and patients with Non-Small Cell Lung Cancer will undergo \[18F\]F-AraG dynamic imaging on the uEXPLORER total body Positron Emission Tomography/Computerized Tomography scanner to obtain preliminary data regarding pharmacokinetics and early biodistribution images.

Detailed description:
\[18F\]F-AraG, a fluorine-18 labeled analog of an FDA approved drug (Nelarabine) is a new imaging tracer targeted at imaging activated T-cells. Given that immunotherapeutic strategies, in particular immune checkpoint antibodies, focus on the generation of T-cell-based antitumor immunity, uptake of \[18F\]F-AraG within the tumor is hypothesized to correlate with T-cell mediated immune response seen in the biopsy samples of cancer patients treated with immune checkpoint blockade. Correlation of pre- and post-treatment intratumoral immune infiltration by means of PET imaging will guide the development of future clinical trials investigating the role of \[18F\]F-AraG in the monitoring of anti-tumor immune responses. Therefore, proper quantification of \[18F\]F-AraG uptake in tumor lesions, and understanding its relation with physiologic uptake in background tissues is important. Note: checkpoint therapy in this study is standard-of-care and is not under investigation.

Available PET/CT scanners can obtain dynamic images only on a portion of the body as large as their axial field of view, generally anywhere between 15-30 cm. The 194 cm long uEXPLORER total-body PET scanner is the world's first device to offer the ability to tomographically image all parts of the body simultaneously. Thus, the uEXPLORER PET/CT (now commercially available and with FDA 510(k) clearance) is the only scanner in the world capable of acquiring total-body dynamic images.

In this pilot study, 2-4 healthy volunteers will undergo \[18F\]F-AraG dynamic imaging on the uEXPLORER total body PET/CT scanner to obtain preliminary data regarding pharmacokinetics and early biodistribution images. In addition, 2-4 patients with NSCLC and planned for standard-of-care PD-1/PD-L1 immunotherapy will undergo \[18F\]F-AraG dynamic imaging similarly on the uEXPLORER total body PET/CT scanner to obtain data regarding pharmacokinetics of the tracer in tumor lesions in the context of normal tissue uptake. An optional second similar scan will be performed 7-14 days after the first dose of immunotherapy to explore and document any treatment related changes in \[18F\]F-AraG uptake and kinetics.

The study and data collected will be important to recommend an ideal time to acquire a whole body static scan using conventional and widely available PET/CT scanners for adequate tumor to background contrast and quantification, which in turn, will be essential for further clinical development of \[18F\]F-AraG to aid the monitoring of anti tumor immune responses.

Arms: arm 1: Study participants will undergo a single dynamic \[18F\]F-AraG PET/CT scan (of duration up to 90-minutes) on the uEXPLORER PET/CT scanner. There will be a follow-up visit or call 7 days after the scan to assess any adverse events that could be attributed to either the scan or the administration of \[18F\]F-AraG. arm 2: Study participants with NSCLC who are planned to receive PD-1/PD-L1 immunotherapy will undergo a pre-therapy dynamic \[18F\]F-AraG PET/CT scan, and an optional post-therapy (first dose only) dynamic \[18F\]F-AraG PET/CT scan on the uEXPLORER total-body scanner.
Interventions: intervention 1: [18F]F-AraG Imaging
Intervention descriptions: intervention 1: Total body PET imaging using \[18F\]F-AraG

Protocol documents:
Prot_SAP_000.pdf: 
[18F]F-ARAG/NSCLC 
 
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A PILOT STUDY OF [18F]F-ARAG PHARMACOKINETICS IN TUMORS AND NON-
MALIGNANT TISSUE USING DYNAMIC TOTAL BODY PET IMAGING IN 
HEALTHY SUBJECTS AND IN PATIENTS WITH NON-SMALL CELL LUNG 
CANCER (NSCLC) 
Study Number: 
CST-FARAG-203   
Indication: 
Non-Small Cell Lung Cancer (NSCLC) 
Phase: 
Pilot 
Funding Source(s): 
Cellsight 
Agent / Modality: 
[18F]F-ARAG/TOTAL BODY PET IMAGING 
Coordinating Center: 
Department of Radiology 
EXPLORER Molecular Imaging Center 
3195 Folsom Blvd, Suite 120 
Sacramento, CA 95816 
Phone: 916-731-9000 
Fax: 916-451-0119 
 
Principal Investigator: 
Simon R. Cherry, Ph.D. 
Professor 
Department of Biomedical Engineering and  
Department of Radiology 
University of California, Davis 
3195 Folsom Blvd, Suite 120, Sacramento, CA 95817 
Telephone: (916) 731-9010 
Email: srcherry@ucdavis.edu 
Co-Principal 
Investigator: 
Megan Daly, MD  
Department of Radiation Oncology  
University of California Davis Comprehensive Cancer Center 
School of Medicine  
4501 X Street, G-140 Sacramento, CA 95817  
Telephone: (916) 734-5428  
Email: medaly@ucdavis.edu 
IND Sponsor: 
Cellsight 
IND # : 
123591 
Version:  
1.0:  06.08.2021  
1.1:  09.17.2021 
1.2:  05.03.2022 
1.3:  06.30.2022 
1.4:  04.23.2024 


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PROTOCOL SIGNATURE PAGE 
 
Protocol Number: CST-FARAG-203 
Protocol Title: A Pilot Study of [18F]F-ARAG Pharmacokinetics in Tumors and Non-Malignant 
Tissue using Dynamic Total Body PET Imaging in Healthy Subjects and in Patients with Non-
Small Cell Lung Cancer (NSCLC) 
I have read this protocol and agree that it contains all necessary details for carrying out this study. 
I will conduct the study as outlined herein and will complete the study within the time designated, 
in accordance with all stipulations of the protocol and in accordance with Good Clinical Practices, 
local regulatory requirements, and the Declaration of Helsinki.  
I will provide copies of the protocol and all pertinent information to all individuals responsible to 
me who assist in the conduct of this study. I will discuss this material with them to ensure that they 
are fully informed regarding the study agent(s) and the conduct of the study.  
 
Simon R. Cherry, PhD_              
Investigator Name (print)                          
 
__________________________________ 
Investigator Signature  
 
__________________________________ 
Date 
 
 
 


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SCHEMA 
 
 
Study Flow Diagram (Healthy Subjects) 
 
 
 
 
 
Study Flow Diagram (NSCLC Subjects) 
 
 
NOTES:  
1. 
IMMUNOTHERAPY IS NOT A PART OF THIS STUDY BUT IS A PART OF SOC TREATMENT OF THESE PATIENTS 
2. 
THE POST-TREATMENT [18F]F-ARAG PET/CT SCAN IS OPTIONAL FOR PATIENTS 
Name of Sponsor/Company: CellSight Technologies 
Name of Study Product: [18F]F-AraG 
Protocol Number: CST-FARAG-203 
 
Indication:  
• Healthy subjects  
• non-small cell lung cancer (NSCLC) patients  
Title of Study: 
A pilot study of [18F]F-AraG pharmacokinetics in tumors and non-malignant tissue using dynamic total body PET imaging in healthy subjects and in patients with 
non-small cell lung cancer (NSCLC). 
Study Center:  UC Davis Comprehensive Cancer Center 
Planned Number of Subjects:  
2-4 healthy subjects 
2-4 NSCLC subjects 
Study Development Phase:  
Phase I/II 
Study Outcome Measures: 
• 
Quantitative assessment of [18F]F-AraG biodistribution in healthy tissues as a function of time. 
• 
Quantitative assessment of [18F]F-AraG biodistribution in tumor lesions relative to non-malignant tissues in NSCLC subjects as a function of time. 
• 
Recommended post-infusion time window to acquire a static [18F]F-AraG PET/CT scan. 
• 
Quantitative assessment of change in PET signal pre- and post-  first dose of PD-1/PD-L1 immunotherapy. 


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TABLE OF CONTENTS 
 
PROTOCOL SIGNATURE PAGE ..............................................................................................2 
SCHEMA ........................................................................................................................................3 
TABLE OF CONTENTS ..............................................................................................................4 
LIST OF TABLES .........................................................................................................................7 
LIST OF FIGURES .......................................................................................................................7 
LIST OF ABBREVIATIONS .......................................................................................................8 
1. 
BACKGROUND ..............................................................................................................10 
1.1 
Therapy Approaches for NSCLC ...........................................................................10 
1.2 
Immune-Checkpoint Blockade Immunotherapy Approaches ................................10 
1.3 
Need for Tumor Response Assessment .................................................................10 
1.4 
A Specific T-Cell Activation Imaging Agent for Tumor Response Assessment ..10 
1.5 
Investigational Agent: [18F]F-AraG .......................................................................11 
1.5.1 
Preclinical Characterization ..................................................................11 
1.5.2 
Clinical experience ................................................................................13 
2. 
STUDY RATIONALE .....................................................................................................15 
3. 
OBJECTIVES ..................................................................................................................17 
3.1 
Primary Objectives.................................................................................................17 
3.2 
Secondary Objectives.............................................................................................17 
4. 
STUDY POPULATION ..................................................................................................17 
4.1 
Inclusion Criteria ...................................................................................................17 
4.2 
Exclusion Criteria ..................................................................................................18 
4.3 
Subject recruitment ................................................................................................19 
4.3.1 
NSCLC Subjects: ..................................................................................19 
4.3.2 
Healthy Subjects: ..................................................................................19 
5. 
STUDY DESIGN ..............................................................................................................19 
5.1 
Study Calendar .......................................................................................................20 
5.2 
Participant Duration ...............................................................................................21 
6. 
MATERIALS AND METHODS ....................................................................................22 
6.1 
Study DRUG: [18F]F-AraG ....................................................................................22 
6.1.1 
Manufacture ..........................................................................................22 
6.1.2 
Availability ............................................................................................22 


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6.1.3 
Agent Ordering......................................................................................23 
6.1.4 
Study Treatment Accountability ...........................................................23 
6.1.5 
Dispensing [18F]F-AraG ........................................................................23 
6.2 
uEXPLORER PET/CT Scan ..................................................................................24 
7. 
RISKS TO SUBJECTS....................................................................................................24 
7.1.1 
Risks from [18F]F-AraG PET/CT scan ..................................................24 
7.1.2 
Radiation Risk .......................................................................................26 
8. 
POTENTIAL BENEFITS TO SUBJECTS ...................................................................27 
9. 
CONCOMITANT MEDICATIONS ..............................................................................27 
10. 
OUTCOME MEASURES AND ANALYSIS ................................................................27 
10.1 
Physiological Time-Activity Curves of [18F]F-AraG Uptake within Healthy 
Tissues....................................................................................................................27 
10.2 
Time-Activity Curves of [18F]F-AraG Uptake within Tumors and Background 
Tissues....................................................................................................................27 
10.3 
Recommended time post [18F]F-AraG infusion to acquire a single static 
PET/CT scan ..........................................................................................................28 
10.4 
Change in PET signal pre- and post- first dose of PD-1/PD-L1 
immunotherapy ......................................................................................................28 
10.5 
Safety Outcome Measures .....................................................................................28 
10.6 
Efficacy Outcome Analysis ...................................................................................28 
11. 
STATISTICAL METHODS AND DATA ANALYSIS ................................................29 
11.1 
Number of Subjects................................................................................................29 
11.2 
Scan Data ...............................................................................................................29 
11.3 
General Statistical Considerations .........................................................................29 
11.4 
Analysis populations ..............................................................................................29 
11.4.1 
Efficacy population ...............................................................................29 
11.4.2 
Per-protocol (PP) Population ................................................................29 
11.4.3 
Safety Population ..................................................................................29 
11.5 
Statistical Methods .................................................................................................29 
11.5.1 
Subject Disposition ...............................................................................29 
11.5.2 
Demographics and baseline characteristics analysis .............................30 
11.5.3 
Concomitant Medications/Therapies ....................................................30 
11.5.4 
Medical history......................................................................................30 
11.5.5 
Study Treatment Compliance ................................................................30 
 


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12. 
SAFETY REPORTING OF ADVERSE EVENTS .......................................................30 
12.1 
Assessment of Safety .............................................................................................30 
12.2 
Adverse Events ......................................................................................................30 
12.3 
Reporting of Adverse Events .................................................................................31 
12.4 
Methods and Timing for Assessing and Recording Safety Variables ...................31 
12.5 
Assessment of Adverse Events ..............................................................................31 
12.6 
Causality ................................................................................................................32 
12.7 
Reporting Requirements for SAEs .........................................................................33 
13. 
QUALITY CONTROL AND QUALITY ASSURANCE .............................................33 
13.1 
Monitoring Requirements ......................................................................................33 
13.2 
Acceptability of Case Report Forms ......................................................................34 
13.3 
Modification of Protocol ........................................................................................34 
13.4 
Reporting Protocol Deviations ...............................................................................34 
13.5 
Subject Premature Withdrawal from Study ...........................................................34 
14. 
DATA AND SAFETY MONITORING COMMITTEE ..............................................35 
15. 
ETHICAL CONSIDERATIONS AND ADMINISTRATIVE PROCEDURES ........36 
15.1 
Ethics and Good Clinical Practice .........................................................................36 
15.2 
IND Holder Information ........................................................................................37 
15.3 
Institutional Review Board/Independent Ethics Committee..................................37 
15.4 
Informed Consent...................................................................................................37 
15.5 
Sharing of Results with Subjects ...........................................................................38 
15.6 
Disclosure and Confidentiality ..............................................................................38 
15.7 
Declaration of Helsinki ..........................................................................................39 
15.8 
Compensation for Research-Related Injury ...........................................................39 
15.9 
Economic Burden to Subjects ................................................................................39 
16. 
REFERENCES .................................................................................................................40 
17. 
APPENDICES ..................................................................................................................42 
Appendix 1: ECOG and Karnofsky Performance Status Scores1,2  ...................................42 
Appendix 2: Study Registration and Participant visits ......................................................43 
 
 
 


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LIST OF TABLES 
Table 1: Study Schedule of Events (Healthy Volunteers) .............................................................20 
Table 2: Study Schedule of Events (NSCLC subjects) ..................................................................21 
Table 3: CTCAE v5.0 General Guidelines ....................................................................................32 
 
LIST OF FIGURES 
Figure 1:  [18F]F AraG accumulation in activated T cells. ............................................................12 
Figure 2: Visualization of endogenously induced anti-tumor immune response ..........................13 
Figure 3: Whole body [18F]F AraG PET image in a healthy volunteer. ........................................14 
Figure 4: [18F]F-AraG PET/CT images pre and post Anti PD 1 Ab therapy. ................................15 
 
 
 
 
 


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LIST OF ABBREVIATIONS 
% 
 
Percent 
AE 
 
Adverse Event 
ANCOVA 
Analysis of Covariance 
BMI 
 
Body Mass Index 
BUN 
 
Blood Urea Nitrogen 
CBC 
 
Complete Blood Count 
CFR 
 
Code of Federal Regulations 
CRF 
 
Case Report Form 
CFR 
 
Code of Federal Regulations 
CRO 
 
Contract Research Organization 
CT 
 
Computed Tomography 
CTL 
 
Cytotoxic T-Lymphocytes 
CTCAE 
Common Terminology criteria for Adverse events 
CV 
 
Curriculum vitae 
DLT 
 
Dose Limiting Toxicity 
DP 
 
Drug Product 
DSMC  
Data Safety and Monitoring Committee 
ECG 
 
Electrocardiogram 
ECOG  
Eastern Cooperative Oncology Group 
FDA 
 
Food and Drug Administration 
FDG 
 
Fluorine-18-flurodeoxyglucose 
g/dL 
 
grams/deciliter 
GCP 
 
Good Clinical Practices 
GLP 
 
Good Laboratory Practice 
GMP 
 
Good Manufacturing Practices 
HPB 
 
Human Peripheral Blood 
HIPAA  
Health Insurance Portability and Accountability Act 
HR 
 
Heart Rate 
IA 
 
Interim Analysis 
ICF 
 
Informed Consent Form 
ICH 
 
International Conference on Harmonization 
IHC 
 
Immunohistochemistry 
IND 
 
Investigational New Drug 
IEC 
 
Independent Ethics Committee 
IP 
 
Investigational Product 
IRB 
 
Institutional Review Board 
ITT 
 
Intent-to-Treat 
IUD 
 
Intra Uterine Device 
IV 
 
Intravenous 
Kg 
 
Kilograms 
Mg 
 
Milligram 
mCi 
 
MilliCurie 
MRI 
 
Magnetic resonance imaging 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg/dL  
Milligram/deciliter 
mmol/L 
Millimole/Liter 


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msec 
 
Milliseconds 
NSCLC 
Non-Small Cell Lung Cancer 
PBMC  
Peripheral Blood Monocyte Cells 
PD1 
 
Programmed cell death protein 
PDL1  
Programmed cell death protein ligand 
PET 
 
Positron emission tomography 
PI 
 
Principal Investigator 
PK 
 
Pharmacokinetics 
PP 
 
Per Protocol 
RBC 
 
Red Blood Cells 
RECIST 
Response evaluation criteria in solid tumors 
RR 
 
Respiration Rate 
SAE 
 
Serious Adverse Event 
SAP 
 
Statistical Analysis Plan 
SD 
 
Standard Deviation 
SOC 
 
Standard of Care 
SOP 
 
Standard Operating Procedures 
SUV 
 
Standardized uptake value 
TBD 
 
To be determined 
TEAE  
Treatment Emergent Adverse Event 
TV 
 
Treatment Visit 
Tx 
 
Treatment, Cancer Treatment 
U/L 
 
Units/Liter 
USA 
 
United States of America 
USP 
 
United States Pharmacopeia 
WBC  
White Blood Cells 
WBS 
 
Whole Body Scan 
WHO  
World Health Organization 
μL 
 
Microliter 
 
 


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 BACKGROUND 
 
Therapy Approaches for NSCLC 
Lung cancer is the leading cause of cancer-related deaths in both men and women in the US. 
(https://seer.cancer.gov/statfacts/html/lungb.html). The majority of NSCLC patients present with 
advanced or metastatic disease, which is not amenable to surgical resection.  
Immunotherapy has attracted much attention in recent years, since (i) identification of molecularly-
defined tumor antigens (TA) [1, 20] has provided well defined moieties to be used as immunogens 
and as markers to monitor the immune response; (ii) characterization of the molecular steps leading 
to an immune response [5, 6] has facilitated the development of effective immunization strategies; 
and (iii) availability of cytokines has provided reagents to modulate the immune response. Because 
of the general belief that T cells play a major role in the control of tumor growth [15, 16], the 
application of T cell-based immunotherapy has been emphasized.  
 
Immune-Checkpoint Blockade Immunotherapy Approaches 
Immunotherapies have changed the treatment strategy of some types of tumor including melanoma 
and, more recently, non-small-cell lung cancer (NSCLC). Immune checkpoints are crucial for the 
maintenance of self-tolerance and it is known that some tumors use checkpoint systems to evade 
antitumor immune response. The treatment of advanced NSCLC by immunotherapy, such as 
immune-checkpoint blockade targeting the programmed cell death protein-1 (PD1/PDL1), has led 
to significant clinical benefit either as monotherapy or in combination therapy [4]. 
 
Need for Tumor Response Assessment 
The landscape of novel cancer therapies is undergoing fundamental changes, with great promise 
in the immunotherapy trials as illustrated by the United States Food and Drug Administration 
(FDA) approval of multiple checkpoint inhibitors for various cancer indications, a monoclonal 
antibody (mAb), ipilimumab, for treatment of metastatic melanoma [12] and a vaccine for prostate 
cancers as the first vaccine against non-viral cancers [13]. There is a pressing need for accurate, 
timely assessment of immunotherapy treatment response in cancer patients to improve clinical 
management and facilitate drug development. A standard for response assessment is measuring 
tumor size with CT or MR and then classifying tumor size reduction according to RECIST [8]. 
RECIST and other standard response measures are ill suited to monitor response to 
immunotherapy, largely due to “pseudoprogression” caused by immune mediated increase in 
contrast enhancement. However, molecular imaging can measure important biologic responses 
that precede tumor size reduction, such as cellular metabolism, proliferation, and vascularity. 
 
A Specific T-Cell Activation Imaging Agent for Tumor Response Assessment 
Early preclinical and clinical studies have shown promise for immunotherapy treatments for 
several malignancies [22]. Immunotherapy is expected to grow in importance; however, it presents 


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difficult challenges for response assessment. For instance, successfully treated tumors may 
actually increase in size after therapy due to inflammation and only later shrink [25]. RECIST 
criteria [8] designed to detect early effects of cytotoxic agents by size reduction, or the more 
recently proposed immune-related response criteria (irRC) [19] do not allow an early assessment 
of immunotherapeutic response since both depend on tumor size change. Furthermore, FDG PET 
is confounded by inflammatory effects causing hypermetabolism [2, 11]. Thus, it is imperative to 
develop new imaging and analysis protocols to evaluate immune-checkpoint blockade approaches.  
A method that evaluates T cell activation would permit an assessment of a basic first step in the 
process of assessing immunotherapy efficacy.  
 
Investigational Agent: [18F]F-AraG 
CellSight Technologies (CST), Inc. is a company that is developing a suite of PET tracers targeted 
at visualizing immune response early in a patient's immunotherapy regimen.  Their lead PET 
imaging tracer targeted at imaging activated T-cells is a fluorine-18-labeled analog of an 
FDA-approved drug Nelarabine [18F]F-AraG, trade name VisAcT.  VisAcT is independent of the 
type of immunotherapy regimen being administered - adoptive cell therapy, checkpoint inhibitors, 
cancer vaccines or a combination of immunotherapy and conventional medicines.  VisAcT is 
relatively specific to activated T-cells that are critical to any immune modulated therapy.  In vivo, 
real time imaging of activated T-cells in solid tumors before and at a timepoint during and after 
checkpoint inhibitor therapy (CkIT therapy) can help understand the effects of check point 
blockade therapy.  Additionally, in vivo whole-body imaging of activated T-cells can provide 
critical information about the effect of immunomodulation in autoimmune diseases, as well as help 
their prediction as adverse events.   
1.5.1 Preclinical Characterization 
Molecular imaging of immune activation by positron emission tomography (PET) is a potential 
noninvasive strategy to monitor immune activation after treatment with immunotherapy.  
Increased activity of nucleoside salvage pathways has been associated with the proliferation of 
adaptive and innate immune cells [10, 24].  In preclinical models of cancer and autoimmunity, the 
PET probe [18F]–2-fluoro-d-(arabino-furanosyl)cytosine ([18F]-FAC), which targets the 
deoxycytidine salvage pathway, was shown to localize to sites of immune activation [21] and is 
predominantly accumulated in proliferative CD8+ T-cells [17]. 
Recently, a radiofluorinated AraG imaging agent, [18F]F-AraG(2′-deoxy-2′-fluoro-9-β-D-arabino-
furanosylguanine;  trade name VisAcT) was synthesized [18] with a goal of development for 
human use.  F-AraG is a fluorinated purine derivative with selective T-cell toxicity.  A 
water-soluble AraG prodrug, Nelarabine, is FDA approved for the treatment of relapsed T-cell 
acute lymphoblastic leukemia and T-cell lymphoblastic lymphomas [7]. [18F]F-AraG 
preferentially accumulates in murine and human activated T-cells than in naive T-cells (Figure 1).  


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[18F]F-AraG was evaluated in three different preclinical models: rheumatoid arthritis [9], GvHD 
[23], colon cancer [14]. 
Figure 1:  [18F]F AraG accumulation in activated T cells. 
  
Figure 1:  [18F]F-AraG preferentially accumulates in activated T-cells than in naive T-cells.  A) Uptake of 
[18F]F-AraG in human and mouse primary T-cells post-stimulation.  B) Pan T-cells were isolated from spleen and 
lymph nodes of mice.  Untreated cells as well as CD3/CD28 activated T-cells (48 hours) were incubated with 
[18F]F-AraG before subcutaneous implantation into the shoulders before PET/CT imaging. 
The accumulation of [18F]F-AraG in human activated T-cells is also significantly higher than other 
immune cells, including B cells, macrophages, and dendritic cells [14].  Furthermore, 
endogenously induced anti-tumor immune response in a viral induced rhabdomyosarcoma (MSV) 
mouse model was correlated with enhanced [18F]F-AraG uptake within the tumors (Figure 2A).  
Analysis of isolated tumors showed that tracer preferentially accumulated in activated CD8+ 
T-cells (Figure 2B). 
 
 


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Figure 2: Visualization of endogenously induced anti-tumor immune response 
Figure 2:  Visualization of endogenously induced anti-tumor immune response in a viral induced rhabdomyosarcoma 
(MSV) mouse model with [18F]F-AraG PET.  A) Viral induced rhabdomyosarcoma was implanted in the left hindleg, 
and P815 mastocytoma (control) was implanted in the right shoulder.  PET/CT was performed on Day 14 during the 
peak anti-tumor immune response in the rhabdomyosarcoma model.  B) CD8+, CD4+ and C19+ cells were isolated 
from rhabdomyosarcoma tumor one hour after probe injection for radioactivity assay. Lymphocytes take up more than 
80% of tumor associated [18F]F-AraG, with CD8+ and CD4+ cells acquiring the largest portion of the tracer (72%). 
The low uptake in B cells (CD19) is only observed in mice. Human B cells do not accumulate the tracer.  C) FACS 
analyses of the isolated lymphocytes showed an activated phenotype (CD44+ CD62L-) in majority of CD8+ 
(79.9±11.5) and CD4+ cells (88.3±11.7). Error bars represent standard deviation.  
1.5.2 Clinical experience 
The first-in-human study of [18F]F-AraG was performed at UCSF in 2015 (abstract of meeting 
presentation available here:   
http://www.wmis.org/meetings/archives-of-past-meetings/wmic-2015-first-in-human-study-3/).  
[18F]F-AraG was administered at a subpharmacologic, tracer microdose consistent with imaging 
practices in six healthy volunteers (3 males and 3 females).  The distribution of the tracer was 
evaluated over the first 4 hours after injection.  A representative whole body PET/MR image in a 
healthy volunteer is shown in Figure 3 ([23]; [18F]F-AraG Investigator’s Brochure).  The tracer 
was well tolerated by all patients and there were no > Grade 1 adverse events (AE).  The only AE 
that occurred in more than 1 volunteer was positive white blood cell (WBC) esterase in the 
urinalysis without urinary symptoms.  Normal uptake was seen in the clearance organs: liver, 
kidneys and bladder.  There appeared to be uptake in the thyroid and parotid glands, as well as 


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limited accumulation in the cardiac muscle.  In these first-in human studies, no additional drugs 
were administered to subjects as the biodistribution was determined for radiation dose estimates.  
[23].  
Figure 3: Whole body [18F]F AraG PET image in a healthy volunteer. 
 
 
 
Figure 3:  Maximum intensity projection (MIP) of a whole body [18F]F-AraG PET image of a healthy volunteer 
acquired 90 minutes post infusion.  
 [18F]F-AraG is currently being tested in several Phase I/II clinical trials.  The clinical trials aim to 
evaluate the use of [18F]F-AraG in cancer patients undergoing immunotherapy. Cancer types 
include solid tumors of all types including, among others, lung cancer, melanoma, breast cancer 
and head & neck cancer. Non-oncology focused trials include an HIV trial at UCSF to help see 
differences in repositories of T cells in HIV patients and a trial at Stanford is determining if 
[18F]F-AraG will be useful as an early predictor of Graft vs Host Disease.  
Investigators from Stanford have reported early clinical evidence that [18F]F-AraG PET scans 
demonstrate imaging of activated T-cells in vivo.  In a study that aims to evaluate immunological 
response to Anti-PD-1 treatment in squamous cell carcinoma of the head and neck (SCCHN), 


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investigators reported a correlation in the change in total SUV and change in the CD8+T-cells post 
PD-1 antibody infusion (Figure 4). 
Figure 4: [18F]F-AraG PET/CT images pre and post Anti PD 1 Ab therapy. 
 
Figure 4:  [18F]F-AraG PET/CT images of 2 SCCHN patients pre and post Anti-PD-1 Ab therapy.  [18F]F-AraG signal 
increased dramatically after only one injection of PD-1 Ab in Patient A.  FACS analysis revealed a higher proportion 
of both CD8+ cells and higher expression of CD38 activation marker after one treatment.  In Patient B, there was not 
a significant increase in total SUV in VOI and correspondingly there was not an increase in the CD8+ cells as analyzed 
by FACS.  Bar graphs show proportion of cells expressing CD8 and CD38 markers in tissue samples pre and post Ab 
therapy in patient A and B. 
 
 STUDY RATIONALE 
Given that immunotherapeutic strategies, in particular immune checkpoint antibodies, focus on the 
generation of T-cell-based antitumor immunity, uptake of [18F]F-AraG within the tumor is 
hypothesized to correlate with T-cell mediated immune response seen in the biopsy samples of 
cancer patients treated with immune checkpoint blockade. Correlation of pre- and post-treatment 
intratumoral immune infiltration by means of PET imaging will guide the development of future 


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clinical trials investigating the role of [18F]F-AraG in the monitoring of anti-tumor immune 
responses. Therefore, proper quantification of [18F]F-AraG uptake in tumor lesions, and 
understanding its relation with physiologic uptake in background tissues is important. Note: 
checkpoint therapy in this study is standard-of-care and is not under investigation. 
The distribution of radiotracer activity depends on post-injection imaging time for both anatomical 
structures and pathologic processes. Anatomic structures with physiologic uptake and pathologic 
abnormalities are likely to be characterized by distinct time-activity curves [3]. Therefore, the 
pharmacokinetic relationship between tumor activity and a variety of tissue background activity is 
important, which is best understood from dynamic images. Dynamic imaging of cancer subjects 
pre- and post-treatment is expected to provide data to establish this relationship between tumor 
and background, as well as the effect of treatment on the relationship.  
While understanding tumor vs background activity in cancer patients is important, such subjects 
are likely to have prior or ongoing treatment, which may affect accurate baselining. Therefore, 
understanding normal tissue activity in healthy volunteers in whom radiotracer distribution is 
likely unencumbered by any effect of prior or ongoing treatment can be important to establish 
baseline dynamic data. In addition, healthy volunteers are likely to tolerate the long dynamic scan 
better than cancer subjects, improving the chances of obtaining standard baseline data.      
Available PET/CT scanners can obtain dynamic images only on a portion of the body as large as 
their axial field of view, generally anywhere between 15-30 cm. The 194 cm long uEXPLORER 
total-body PET scanner is the world’s first device to offer the ability to tomographically image all 
parts of the body simultaneously. Thus, the uEXPLORER PET/CT (now commercially available 
and with FDA 510(k) clearance) is the only scanner in the world capable of acquiring total-body 
dynamic images.  
In this pilot study, 2-4 healthy volunteers will undergo [18F]F-AraG dynamic imaging on the 
uEXPLORER total body PET/CT scanner to obtain preliminary data regarding pharmacokinetics 
and early biodistribution images. In addition, 2-4 patients with NSCLC and planned for standard-
of-care PD-1/PD-L1 immunotherapy will undergo [18F]F-AraG dynamic imaging similarly on the 
uEXPLORER total body PET/CT scanner to obtain data regarding pharmacokinetics of the tracer 
in tumor lesions in the context of normal tissue uptake. An optional second similar scan will be 
performed 7-14 days after the first dose of immunotherapy to explore and document any treatment 
related changes in [18F]F-AraG uptake and kinetics. 
The study and data collected will be important to recommend an ideal time to acquire a whole 
body static scan using conventional and widely available PET/CT scanners for adequate tumor to 
background contrast and quantification, which in turn, will be essential for further clinical 
development of [18F]F-AraG to aid the monitoring of anti-tumor immune responses. 
 


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 OBJECTIVES 
The study is exploratory in nature with the following objectives: 
 
Primary Objectives 
• To obtain preliminary data on the baseline whole-body pharmacokinetics of [18F]F-AraG 
physiologic uptake in various healthy tissues using the uEXPLORER PET/CT scanner. 
 
• To obtain preliminary data on the pharmacokinetics of [18F]F-AraG pathologic uptake in 
tumor lesions relative to uptake in background tissues in NSCLC subjects using the 
uEXPLORER PET/CT scanner. 
  
• To recommend an ideal time window post [18F]F-AraG infusion to acquire static whole-
body scans using standard PET scanners used in clinical care. 
 
Secondary Objectives 
• To assess [18F]-AraG uptake in NSCLC before and after the first dose of PD-1/PD-L1 
immunotherapy. 
 
 STUDY POPULATION 
 
Inclusion Criteria 
Subjects are eligible if they meet ALL of the following criteria: 
For all subjects: 
1. 
Age ≥ 18 years.  
2. 
Ability to understand the purposes and risks of the trial and has signed an IRB-approved 
informed consent form.  
3. 
Willingness and ability to comply with all protocol required procedures.  
4. 
For men and women of child-producing potential, willingness to use of effective double 
barrier contraceptive methods during the study, up to 1 day after the last administration of 
the investigational product. 
For NSCLC subjects only: 
5. 
Patients with histologically confirmed advanced, locally advanced, or localized NSCLC. 
6. 
Planned to undergo treatment with a PD-1 or PD-L1 inhibitor either as 1) monotherapy or 
as combination therapy with concurrent chemotherapy as treatment for 
advanced/metastatic disease 2) As consolidation therapy following chemoradiation for 
locally advanced disease or 3) As induction therapy either as monotherapy or 
combination therapy with chemotherapy prior to planned surgical resection 


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7. 
At least 1 tumor lesion > 1 cm (cannot be only in liver) documented on CT or MRI or 
FDG-PET/CT (RECIST criteria 1.1; >1.5 cm for nodal lesions) within 45 days prior to 
scan date.  
8. 
Per investigator’s assessment and in consultation with oncologists, at least one eligible 
lesion must be sufficiently separated from tissues with known high [18F]F-AraG uptake, 
such as salivary glands, bladder, liver and kidneys so that quantification will be feasible. 
9. 
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 
10. Meeting all clinical safety lab values per institution’s standard of care, or Investigator’s 
discretion, for patients receiving cancer treatment. 
 
Exclusion Criteria 
Subjects are not eligible if they meet ANY of the following criteria: 
1. Serious comorbidities (nonmalignant disease or other conditions) that in the opinion of the 
investigator could compromise protocol objectives. 
2.  History of recent COVID-19 infection within the last 2 months OR history of COVID 
requiring hospitalization with lung injury at Investigator’s discretion 
3. Subjects with a diagnosis of immunodeficiency or receiving systemic steroid therapy or any 
other form of immunosuppressive therapy within 7 days prior to the scan 
4. Subjects receiving therapy with nucleoside analogs including but not limited to: acyclovir, 
valaclovir, penciclovir, famciclovir, ganciclovir, ribavirin, valganciclovir, glanciclovir 
5. Pregnant women or nursing mothers 
6. Body weight more than 240 kg (529 pounds) 
 
For NSCLC subjects only: 
7. Prior Treatment with anti-PD-1/PD-L1 immunotherapy. 
 
For Healthy subjects 
8. No primary care physician 
 
 
 


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Subject recruitment 
4.3.1 
NSCLC Subjects: 
Patients will be recruited by Dr. Daly and other physicians within the UC Davis Cancer Center 
from their clinics.  Dr. Daly regularly sees lung cancer patients as part of her clinical practice.  
The physicians will not be separately screening charts, but will recruit from among their patients.   
 
4.3.2 
Healthy Subjects: 
Up to 4 normal subjects will be recruited by means of a flyer posted in specific areas: the Division 
of Nuclear Medicine (Davis Tower, Ambulatory Care Center (ACC)), the UC Davis Explorer 
Molecular Imaging Center located at 3195 Folsom Blvd, Sacramento, CA, the Radiology 
Academic office (ACC, Suite 3100), and the research laboratories of Dr. Simon Cherry and Dr. 
Jinyi Qi (Main campus, GBSF).  Flyers will be posted in other academic offices at ACC including 
cardiology, ophthalmology, orthopedics, etc. Additionally, the study will be announced on the 
EXPLORER website: https://explorer.ucdavis.edu/ and on the UC Davis Clinical Study Pages site: 
https://studypages.com/ucdavis/ 
 
 STUDY DESIGN 
Protocol CST-FARAG-203 is a pilot study using the uEXPLORER total-body PET/CT system to 
acquire dynamic [18F]F-AraG scan data in healthy individuals and patients with NSCLC.  
Screening will consist of eligibility confirmation, the patient signing the consent form, and any 
assessments outlined in the study calendars below.  This will also include a query about status and 
date of COVID-19 vaccination.   
Eligible healthy subjects will undergo a single dynamic [18F]F-AraG PET/CT scan (of duration up 
to 90-minutes) on the uEXPLORER PET/CT scanner within 28 days of screening or on the day of 
screening if possible and convenient to the subject.  There will be a follow-up visit or call 7 days 
after the scan to assess any AEs that could be attributed to either the scan or the administration of 
[18F]F-AraG. 
Eligible subjects with NSCLC who are planned to receive PD-1/PD-L1 immunotherapy will 
undergo a pre-therapy dynamic [18F]F-AraG PET/CT scan, and an optional post-therapy (first dose 
only) dynamic [18F]F-AraG PET/CT scan on the uEXPLORER total-body scanner.  
For each enrolled patient, [18F]F-AraG will be administered by a licensed Nuclear Medicine 
technologist under the supervision of a board-certified Nuclear Medicine physician (ABNM or 
ABR certified) on an outpatient basis.  It will be administered as a single bolus injection of 5 mCi 
+/-20% IV into a vein. Vital signs will be assessed just prior to and after completion of dynamic 
[18F]F-AraG PET scan.   


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For each scan, the subject will be prepared according to the site’s standard procedures and asked 
to void the bladder immediately prior to imaging. For the scan, an intravenous (IV) line will be 
placed in a vein and the subject will be positioned supine on the scanner table. The PET/CT 
imaging will begin with a low-dose CT scan on the uEXPLORER PET/CT scanner. This CT 
scan will provide information for anatomic localization and attenuation correction purposes.  
[18F]F-AraG will then be infused as above and a 90-minute dynamic PET scan will be performed 
on the uEXPLORER. The IV line will be removed after dynamic acquisition. For subjects who 
may not be able to undergo a 90-minute dynamic scan, a 60-minute dynamic PET scan will be 
performed, followed by a 10-minute static scan starting at 80 minutes post [18F]F-AraG infusion. 
The separate static scan at 80 minutes will be obtained along with an ultra-low-dose CT which is 
needed for attenuation correction of this separate scan. 
The study will be an open label, non-randomized, single arm trial.  Patients and care providers will 
not be blinded to any part of the study.  
 
Study Calendar 
Table 1: Study Schedule of Events (Healthy Volunteers) 
Protocol Assessments 
Visit 11 
Visit 21 
 
Screening 
(Day -28 to Day 0) 
PET/CT scan 
(Day 0) 
Safety Interview 
(Day 7) 
Informed consent 
X 
 
 
Medical History and Physical Examination2 
X 
 
 
Eligibility Assessment  
X 
X 
 
Urine Pregnancy Test3 
X 
X 
 
Concomitant medications  
X 
X 
 
[18F]F-AraG PET/CT imaging 
 
X 
 
Adverse events collection4 
 
X 
X5 
1. 
Visits 1 & 2 can be merged into a single visit done on the same day. 
2. 
Includes vital signs, height, weight, BMI 
3. 
In women of 18-60 years old unless documented hysterectomy or bilateral ovarian removal is available.   
4. 
AE collection: Up to 2 hours of [18F]F-AraG infusion on Day 0; AEs that occur prior to this will be considered baseline.  
5. 
The follow up safety interview can be performed telephonically and does not require a separate in-person visit. 


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Table 2: Study Schedule of Events (NSCLC subjects) 
 
Visit 1 
Visit 2 
Visit 3 
Visit 4Ψ 
 
Protocol Assessments 
Screening 
(Day -28 
to Day 0) 
PET/CT 
scan 
(Day 0) 
 (Day 0-7) 
PET/CT 
(7-14 Days after 
V3) 
Safety Interview 
(7 days after last 
PET/CT scan) 
Informed consent 
X 
 
 
 
 
Medical history and Physical 
Examination2 
X 
 
 
 
 
Eligibility Assessment (including 
eligible lesions assessment) 
X 
X 
 
 
 
ECOG Performance Status 
Assessment 
X 
 
 
 
 
SOC CT/MRI and/or FDG-PET/CT 
collection 
X1 
 
 
 
 
Urine Pregnancy Test3 
X 
X 
 
X 
 
[18F]F-AraG PET/CT imaging 
 
X 
 
X 
 
Administration of PD-1/PD-L1 
Treatment 
 
 
X 
 
 
Adverse events collection4 
 
X 
 
X 
X5 
Concomitant medications  
X 
X 
 
X 
 
1. 
CT or MRI or FDG-PET/CT performed up to 45 days prior to Visit 2 is acceptable. 
2. 
Includes vital signs, height, weight, BMI 
3. 
In women 18-60 years old unless documented hysterectomy or bilateral ovarian removal is available 
4. 
AE collection: Up to 2 hours of [18F]F-AraG infusion on Visits 2 and 4; AEs that occur prior to this will be considered baseline. 
5. 
The follow up safety interview can be performed telephonically and does not require a separate in-person visit. 
Ψ Optional visit 
 
 
Participant Duration 
Healthy volunteer subjects will have up to 3 visits over a period of one to four weeks.  NSCLC 
patients will have up to 4 visits over a period of one to four weeks, prior to and after cancer 
treatment.   
We anticipate enrollment will be completed within 12 months after the start of enrollment and that 
the study will be completed in 2 years.   
 
Participant Compensation 
Participants will be compensated $100 per PET/CT scan in the form of gift cards.  The maximum 
total will be $200 for NSCLC patients and $100 for healthy volunteers.   
 
 
 


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 MATERIALS AND METHODS 
 
Study DRUG: [18F]F-AraG 
6.1.1 
Manufacture  
[18F]fluoride (n.c.a.) in [18O]water is passed through a PS-HCO3 cartridge, eluted with 1 mL of a 
phase transfer catalyst solution containing Kryptofix222 (15 mg) and K2CO3 3.5 mg) in 10:1 
acetonitrile/water.  The K222/K[18F]F complex is heated and dried under Helium at 65 °C for 
3 minutes, followed by heating at 95 ºC for 1 minute.  After cooling to ~50 ºC, a solution 
containing [18F]F-AraG trifylate precursor (6 mg in 1 mL DMSO) is added to the reactor and the 
solution heated to 115 °C for 45 minutes.  After cooling down to ~40 °C, to the reaction mixture 
was added sodium methoxide, and heated at 100 ºC for 10 minutes.  Reaction is cooled to 40 ºC 
and after addition of 0.5 mL of 1 N HCl stirred at 95 ºC for 10 minutes.  The reaction mixture is 
then cooled to 30 ºC and diluted with a solution of 0.5 mL of 1N NaHCO3 in 9.5 mL of water 
(SV3). The solution in the reactor is transferred through 4 × C-18 cartridges via a V31 valve and 
collected in a waste container.  The cartridges are backwashed to the reactor with 2 mL of methanol 
in the pre-HPLC tube.  Methanol is removed under vacuum with the flow of helium at 90 ºC for 
13 minutes.  After cooling the reactor to 30 ºC water is added and the solution transferred through 
a 0.45 µm filter into a pre-HPLC container. 
Crude [18F]F-AraG is injected on to a HPLC Luna C18 semi-preparative reversed-phase column 
(5 µm, 10 × 250 mm).  The desired product fraction (Rt ~ 16 minutes) is collected into the round 
bottom flask pre-filled with 30 mL of water.  The diluted fraction is passed through the C18 plus 
cartridges and rinsed with water (10 mL), then the trapped product is eluted by ethanol (1 mL) into 
a collection vial for subsequent dilution with saline (9 mL).  [18F]F-AraG for Injection is prepared 
by then passing through a 0.22 µm Millex GV sterile filter to a pre-assembled septum-sealed sterile 
collection vial (30 mL) for filtration and sterilization.  The final sterile empty vial, product needle, 
vent needle, 4 mm GV filter for vent and sterile GV filter (33 mm) are assembled in a sterile LFH 
(laminar flow hood).  The final product is released compliant to release specifications as submitted 
to the FDA. No further testing is required at the research site prior to injection. 
[18F]F-AraG will be supplied by Cellsight at no cost to study patients. 
6.1.2 
Availability 
The [18F]F-AraG will be synthesized, on a per scan basis, under cGMP at one of CellSight’s 
identified qualified production sites.  All qualified production sites are FDA-approved clinical 
manufacturers of the tracer. Cellsight carries the IND.  Cellsight submitted all the manufacturing 
CMCs to the FDA for all approved sites.  As needed, the facility staff will be trained by Cellsight 
in synthesizing this radiopharmaceutical. Please refer to CellSight Pharmacy Manual.  
 
 


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6.1.3 
Agent Ordering 
The [18F]F-AraG will be individually requested per subject by Nuclear Medicine research 
coordinators or technologists, under the supervision of the Nuclear Medicine investigators, for 
synthesis under cGMP at  the identified production site. Please refer to CellSight Pharmacy 
Manual.  
6.1.4 
Study Treatment Accountability 
The Investigator or designee will verify the contents of each shipment against the shipping 
documents. A study treatment accountability log will be kept by the Investigator to maintain 
current and accurate inventory records (batch, expiry, and quantity) covering the receipt, 
dispensing and the destruction of all the study treatments.  
At the conclusion of the study, or other situations as applicable (ex. site closure, IP expiry, etc.) 
the Investigator must agree to return or destroy all study materials as instructed by the Sponsor.  
Please refer to CellSight Pharmacy Manual. 
6.1.5 
Dispensing [18F]F-AraG 
The [18F]F-AraG will be ordered and synthesized under cGMP at qualified sites by radiochemistry 
staff in the Nuclear Medicine department.  
Each dose will be manufactured on a per patient, per scan basis, according to the investigator 
physician’s prescription order. Upon receipt, qualified personnel will ensure that the study drug is 
delivered in good condition, inventoried, stored properly, labeled and dispensed in compliance 
with the pharmacy manual, all regulatory agencies and per the investigator physician’s prescription 
order.   
The [18F]F-AraG dose will be measured by the qualified personnel in a dose calibrator prior to 
dispensing. Then the syringe will be placed in a shielded carrier for administration via venous 
infusion. After the dose administration, the qualified personnel will return the syringe for residual 
measurement by the nuclear medicine technologists at the site. Measured radioactivity values and 
times of measurement will be documented, as well as the total injected volume.  
Regulatory agencies require accounting for the disposition of all investigational drugs received by 
each clinical site. Information on drug disposition required by law consists of the date received, 
date dispensed, quantity dispensed, and the patient identification number to whom the drug was 
dispensed. The Investigator is responsible for accounting for all unused study drug and destroying 
all used study drug containers in compliance with the pharmacy manual.  
 
 


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uEXPLORER PET/CT Scan  
For the purpose of this study, [18F]F-AraG PET/CT scan images must only be acquired on the 
uEXPLORER scanner and that scanner must undergo regular Quality Control (QC) checks. 
Documentation of such QC activities must be available upon request or audit. Image acquisition 
will be obtained in list mode and the raw data saved to allow for virtual radioactive dose 
reconstruction at a later date. 
 
 RISKS TO SUBJECTS 
7.1.1 
Risks from [18F]F-AraG PET/CT scan 
In this study, 2-4 healthy subjects and 2-4 NSCLC patients will undergo research PET/CT imaging 
with [18F]F-AraG as specified in the experimental imaging section.  [18F]F-AraG PET imaging has 
been performed on 6 healthy volunteers in a separate study with no drug-related side effects.  In 
addition, [18F]F-AraG has been administered to 13 cancer patients with 7 of those patients getting 
two doses for pre and post immunotherapy scans, also without any drug-related side effects. 
Given the prior clinical safety experience thus far, we expect few, if any, adverse effects from 
[18F]F-AraG administration in this study. Presently there are no standard surrogate biomarkers or 
imaging modalities that can substitute for these procedures.  The alternative will be for the patient 
to withdraw from the imaging study.   
The safety monitoring practices employed by this protocol are adequate to protect the subjects’ 
safety and should detect all Treatment Emergent Adverse Events (TEAEs). An indirect health 
benefit to the subjects enrolled in this trial is the free medical tests received at screening and during 
the study. 
Due to the (up to) 90-minute long scan time through which the participants are expected to remain 
still, the patients may feel discomfort and/or fatigue from laying on the scanner table. In addition, 
they may experience claustrophobia from being inside the scanner bore, which is a partially 
enclosed space. 
Another risk is possible bruising and/or infection at the IV site. 


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Reproductive Risks are associated with PET: (PET) radiotracers studies on the fetus (unborn child) 
have not been done. To avoid risk to the fetus, it is important that female participants not become 
pregnant while they are participating in this research study. Avoiding sexual activity is the only 
certain method to prevent pregnancy. However, if they choose to be sexually active, they should 
use an appropriate “double barrier” method of birth control (such as female use of a diaphragm, 
intrauterine device (IUD), or contraceptive sponge, in addition to male use of a condom) or the 
female should be using prescribed “birth control” pills, injections, or implants. Such birth control 
methods should be used for as specified by their doctor prior to beginning their participation in the 
research study and continues for as long as specified by their doctor after their final study visit. If 
they choose to be sexually active during this study, even with the use of these birth control 
measures pregnancy could still result. The risks of participation in the research PET studies while 
pregnant include potential loss of pregnancy or possible birth defects. If participant is a woman18-
60 years old, they will undergo a urine pregnancy test within 24 hours prior to each PET session 
unless documented hysterectomy or bilateral ovarian removal is available. If participant becomes 
aware that they are pregnant during the course of their participation in this study, they should 
contact immediately the study doctor. 
It is possible that uEXPLORER PET/CT scans may detect false positive findings that may 
require further follow-up (clinical, imaging or surgical) with all the risks associated with these 
follow-up procedures.  The PET/CT images created for this study are for research and are not 
meant to evaluate subject health, as they would be if they were part of a clinical (non-research) 
visit to the doctor or hospital. The images will not receive any routine clinical review by 
radiologists who interpret PET/CT scans. This means that some findings may be overlooked or 
misinterpreted.  However, if the PET/CT technologists do notice findings that cause concern, 
they will notify the Study Radiologist.   Additionally, if a member of the research team notices 
any findings that cause concern while conducting image review for study purposes, they will 
notify the Study Radiologist. The Study Radiologist will conduct a brief review of part of the 
study images for quality purposes.   If the Study Radiologist thinks a clinical problem is present, 
one of the IRB-approved study physicians will discuss these possible problems with the subject 
within 8 weeks or immediately upon recognition of any critical finding that requires immediate 
and/or urgent intervention as described in the Department of Radiology Critical Findings policy 
(full dataset of images are sometimes not available for review in less than 3 days).  Upon written 
request, we will provide the subject with a copy of a subset of their CT images to take to the 
physician of their choosing. A subset of PET images may also be shared with the subject unless 
the images from the study are clinically uninterpretable. In addition, the sponsor may restrict 
sharing of PET images due to the nature of the research protocol or to protect intellectual 
property (e.g. proprietary radiotracers). We will send a standard letter to the designated licensed 
medical provider identified by the subject, unless one of the study physicians is part of the 
subject’s care.  The standard letter will state that (i) the subject’s images were acquired 
exclusively for a research study and incidental findings that may be related to a medical 
condition were observed by a UC Davis radiologist; (ii) the images did not receive any dedicated 


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routine clinical review and findings may have been overlooked or misinterpreted; (iii) the 
subject’s physician can contact the study doctor at any time if there are any concerns regarding 
the study or the subject’s findings.  
7.1.2 
Radiation Risk 
Each patient will receive up to two 5 mCi +/-20% doses of [18F]F-AraG.  Dosimetry assessment 
estimated an effective dose of 0.58 and 0.62 mSv/mCi for males and females, respectively.  Risks 
from the PET/CT itself include additional radiation exposure from the CT attenuation correction 
scan (estimated to be 10 mSv for each low dose CT scan and 1 mSv for each ultra low dose CT 
scan). The table below shows the estimated effective radiation dose received by the subjects in this 
protocol: 
 
Healthy Subjects 
NSCLC Patients 
NSCLC Patients who 
cannot 
undergo 
90 
minutes 
continuous 
scanning 
Low dose CT scan 
10 mSv 
10 mSv 
10 mSv 
Ultra low dose CT scan 
N/A 
N/A 
1 mSv 
[18F]-AraG PET scan 
2.9 +/- 0.29 mSv(male) 
3.1 +/- 0.31 mSv(female) 
2.9 +/- 0.29 mSv(male) 
3.1 +/- 0.31 mSv(female) 
2.9 +/- 0.29 mSv(male) 
3.1 +/- 0.31 mSv(female) 
Total estimated dose 
12.9 +/- 0.29 mSv(male) 
13.1 +/- 0.31 mSv(female) 
12.9 +/- 0.29 mSv(male) 
13.1 +/- 0.31 mSv(female) 
13.9 +/- 0.29 mSv(male) 
14.1 +/- 0.31 mSv(female) 
Number of scans 
1 
2 
2 
Maximum 
estimated 
dose 
13.2 mSv (male) 
13.4 mSv (female) 
26.4 mSv (male) 
26.8 mSv (female) 
27.4 mSv (male) 
27.8 mSv (female) 
 
The total estimated dose from the combined PET/CT examination will be 13.4 mSv or less for 
normal subjects and 27.8 mSv or less for patients with NSCLC. The use of radiation involves 
minimal risk and is required to obtain the desired research information. 
 


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 POTENTIAL BENEFITS TO SUBJECTS 
There will be no direct benefit to the subjects.  The therapy for NSCLC Subjects will not be 
changed based on the [18F]F-AraG PET findings.   
 CONCOMITANT MEDICATIONS  
Subjects must be questioned at each study visit concerning any new medications or changes in 
current medications including over-the-counter and topical medications. All medications and 
therapies administered or taken by the subject beginning 30 days prior to signing the ICF and 
throughout the study will be recorded in the source documents and on the appropriate page of the 
CRF. Intravenous fluid documentation will NOT include IV fluids used to administer medications, 
only the medications administered through the IV fluid will be documented. Intravenous fluids 
used to keep the vein open or used for flushing will also not be documented in the concomitant 
medication CRF. 
For each medication and non-study treatment, the following will be documented: 
 Medication/treatment name (generic name may be used if trade name is unknown) 
 Dose, unit, and frequency of dosing (individual dosages, not total daily dose). Note: Each 
new dose of medication should be recorded as a separate entry, with the exception of 
medications that are given on a sliding scale. For these, it is acceptable to enter the range 
of the dosage, including the start and stop dates for which the specified dosage range was 
used. 
 Route of dosing 
 Indication for use (Indication should include exact medical terminology) 
 The start date  
 The stop date (if medication/therapy is not ongoing) 
 
 OUTCOME MEASURES AND ANALYSIS 
 
Physiological Time-Activity Curves of [18F]F-AraG Uptake within Healthy Tissues 
One of the primary objectives of the study is to obtain baseline pharmacokinetic information in 
the form of [18F]F‑AraG uptake in healthy tissues as a function of time. To achieve this outcome, 
data on [18F]F‑AraG uptake in several tissue types will be collected from healthy subjects. This 
data will be presented in the form of time-activity curves (TAC) generated for each tissue type.   
 
Time-Activity Curves of [18F]F-AraG Uptake within Tumors and Background 
Tissues 
Another objective of the study is to obtain pharmacokinetic information in cancer subjects in the 
form of relative [18F]F-AraG uptake in tumor lesions and background tissues as a function of time. 
To achieve this outcome, data on [18F]F-AraG uptake in tumor lesions and background activity in 


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the same tissues as in Section 10.1 will be collected. This data will be similarly presented in the 
form of time-activity curves (TAC) generated for each tissue type as in Section 10.1, as well as for 
tumor lesions against their background tissues. 
 
Recommended time post [18F]F-AraG infusion to acquire a single static PET/CT 
scan 
The TAC analysis of [18F]F-AraG uptake will provide insight into the earliest time to achieve 
adequate tumor versus non-malignant background tissue activity, as well as time to reach and 
remain in steady state up to 90 minutes. Such information can guide a recommendation for the 
ideal time window for a static [18F]F-AraG PET scan for future trials and potential clinical use. 
 
Change in PET signal pre- and post- first dose of PD-1/PD-L1 immunotherapy 
For NSCLC subjects who undergo two [18F]F-AraG PET/CT scans, the signal at a static time point 
post [18F]F-AraG infusion (obtained from the result of one of the outcome measures; Section 10.3) 
from both scans will be observed for trends.  
 
Safety Outcome Measures 
• Incidence of Treatment-Emergent Adverse Events (AEs). 
• Incidence of withdrawals due to AEs. 
• Serious Adverse Events (SAEs) 
Analyses of safety outcomes will be conducted using the safety population. Adverse events will 
be coded using MedDRA. Treatment Emergent AE’s (TEAE) are defined as events with an onset 
on or after the first treatment. TEAEs will be summarized by treatment group and by stage of the 
study, System Organ Class, and preferred term. The following TEAE summaries will be provided: 
• TEAEs by severity grade 
• TEAEs by relationship to study treatment. 
In addition, separate summaries of serious adverse events, and adverse events resulting in 
discontinuation of study treatment will be presented. 
 
Efficacy Outcome Analysis 
Descriptive statistics will be used to summarize the characteristics of study participants, including 
their age, gender, primary tumor sites and clinical stages, concomitant medications, etc.  Frequency 
tables will be used to summarize categorical variables.  Median and inter-quartile ranges will be 
used to describe no-normally distributed continuous variables.  Mean and standard deviation will 
be used to summarize normally distributed continuous variables. 
Feasibility will be assessed per patient basis.  The percentage of patients who can be successfully 
evaluated by [18F]F-AraG PET imaging will be computed and summarized. 
 


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 STATISTICAL METHODS AND DATA ANALYSIS 
 
Number of Subjects 
The primary goal of this pilot study is to acquire preliminary dynamic [18F]F-AraG scan data in 
healthy individuals and patients with NSCLC. Given the preliminary nature of this study, a power 
calculation was not performed. 2-4 subjects are likely sufficient for a general understanding of 
healthy tissue uptake as a function of time. Similarly, 2-4 NSCLC subjects are considered adequate 
to provide at least one lesion with positive and sufficient tumor uptake of [18F]F-AraG to provide 
a general understanding of tumor tracer kinetics. 
 
Scan Data 
Data from uEXPLORER scanner will be acquired in listmode. Data will be reconstructed using 
manufacturer’s recommendations. Image quality, quantitative comparisons and preliminary 
biodistribution data collection will be performed by means of volumes of interest (VOIs) drawn in 
different organs, tissue types and tumor lesions (in NSCLC subjects). These will be used to 
generate standard uptake values, normalized to body weight (SUV-bw) for the purpose of 
quantitative analysis of spatial as well as temporal tracer distribution. 
 
General Statistical Considerations 
All collected study data will be presented in subject data listings. Descriptive statistics (n, mean, 
standard deviation, median, minimum and maximum) will be presented for continuous variables. 
Frequencies and percentages will be presented for categorical variables.  
 
Analysis populations 
The details of the analysis population to be used for the study are described below: 
11.4.1 
Efficacy population 
The efficacy population is defined as all subjects who have received at least one (up to) 90-
minute dynamic [18F]F-AraG PET scan.  
11.4.2 
Per-protocol (PP) Population 
The Per Protocol (PP) population is defined as the set of subjects who meet the efficacy 
population requirements and were not associated with a major protocol violation.     
11.4.3 
Safety Population 
The Safety population is defined as all subjects receiving at least one dose of [18F]F-AraG.    
 
Statistical Methods 
11.5.1   Subject Disposition  
The disposition of all subjects who sign an ICF will be provided. The numbers of subjects screened, 
enrolled, completed, and discontinued during the study, as well as the reasons for all post-


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enrollment discontinuations will be summarized for healthy and NSCLC subjects respectively. 
Disposition and reason for study discontinuation will also be provided as a by-subject listing.   
11.5.2   Demographics and baseline characteristics analysis  
Demographics and baseline characteristics will be summarized for healthy and NSCLC subjects 
respectively using appropriate descriptive statistics. 
11.5.3   Concomitant Medications/Therapies 
Concomitant medications/therapies will be summarized separately for the Safety population. All 
prior and concomitant medications recorded in the case report form will be coded to all matching 
Anatomic Therapeutic Classification codes using the most recent version of WHO Drug. 
Descriptive summaries, by study group and stage of the study, will be prepared using the coded 
term. All concomitant medications/therapies recorded in the case report form will be listed.   
11.5.4   Medical history 
The medical history will be summarized and/or listed descriptively. 
11.5.5  Study Treatment Compliance 
The study treatment compliance data will be summarized and/or listed descriptively. 
 
 SAFETY REPORTING OF ADVERSE EVENTS 
 
Assessment of Safety 
The Investigator is responsible for the detection and documentation of events meeting the criteria 
and definition of an AE or SAE, as provided in this protocol.  During the study when there is a 
safety evaluation, the Investigator or site staff will be responsible for detecting, documenting and 
reporting AEs and SAEs as detailed in this Section of the protocol.  
 
Adverse Events  
An adverse event (AE) is defined as any unfavorable or unintended sign, symptom, or disease that 
occurs or is reported by the patient to have occurred, or a worsening of a pre-existing condition.  
An adverse event may or may not be related to the study treatment.  
AEs will be elicited through direct questioning and subject reports. Any abnormality in physical 
examination findings or laboratory results that the investigator believes is clinically significant to 
the research subject and that occurred after initiation of the first study treatment will be reported 
as AEs. Abnormal findings that are NOT clinically significant should not be recorded as an AE. 


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Reporting of Adverse Events 
Report initiation for all AEs and serious adverse events (SAEs) will begin immediately after the 
first infusion of [18F]F-AraG (Visit 2) and continue until the Day 7 follow up. The Day 7 adverse 
event assessment may be telephonic and does not require an office visit. All events will be followed 
to resolution or until they are considered to be not clinically significant according to the 
investigator’s judgment.   
All AEs must be recorded in the subject’s medical records and on the CRF. AEs will be reported 
using customary medical terminology along with the following information:  the onset and end 
dates, whether the event is at the site of [18F]F-AraG administration, whether the event is 
considered to be a SAE, the impact the event had on study treatment, the CTCAE grade (intensity) 
of the event, the causality of the event, whether treatment was given as a result of the event, and 
the outcome of the event. 
Serious Adverse Events 
An AE should be classified as an SAE if any of the following criteria are met: 
• It results in death (i.e., the AE actually causes or leads to death). 
• It is life threatening (i.e., the AE, in the view of the investigator, places the subject at 
immediate risk of death. It does not include an AE that, had it occurred in a more severe 
form, might have caused death.). 
• It requires or prolongs inpatient hospitalization. 
• It results in persistent or significant disability/incapacity (i.e., the AE results in 
substantial disruption of the subject’s ability to conduct normal life functions). 
• It results in a congenital anomaly/birth defect in a neonate/infant born to a mother 
exposed to the investigational treatment. 
• It is considered a significant medical event by the investigator based on medical 
judgment (e.g., may jeopardize the subject or may require medical/surgical intervention 
to prevent one of the outcomes listed above). 
 
 
Methods and Timing for Assessing and Recording Safety Variables 
The investigator is responsible for ensuring that all AEs and SAEs that are observed or reported 
during the study are collected and reported to the FDA in accordance with CFR 312.32 (IND Safety 
Reports).  
 
Assessment of Adverse Events 
All AEs and SAEs whether volunteered by the subject, discovered by study personnel during 
questioning, or detected through physical examination, laboratory test, or other means will be 
reported appropriately. Each reported AE or SAE will be described by its duration (i.e., start and 


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end dates), regulatory seriousness criteria if applicable, suspected relationship to the 
investigational treatment (see following guidance), and actions taken. 
The guidelines outlined in CTCAE v5.0 will be used for assessing the intensity of the event. The 
general guidelines for assessing the AE grade appear below.  Full guidelines may be obtained at 
https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_R
eference_5x7.pdf 
 
Table 3: CTCAE v5.0 General Guidelines 
Grade 
Description 
Grade 1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated. 
Grade 2 
Moderate; minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental activities of daily living (ADL)*. 
Grade 3 
Severe or medically significant but not immediately life-threatening; hospitalization 
or prolongation of hospitalization indicated; disabling; limiting self care ADL†. 
Grade 4 
Life-threatening consequences; urgent intervention indicated. 
Grade 5 
Death related to AE.‡ 
*Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc. 
†Self care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden. 
‡Unlike the AE outcome assessment (see Section Error! Reference source not found.), a subject may have more than one 
Grade 5 event. 
 
-Common Terminology Criteria for Adverse Events (CTCAE), v5.0: November 27, 2017 
 
 
Causality 
Adverse events will be assigned a relationship (causality) to the study treatment.  The Investigator 
will be responsible for determining the relationship between an AE and the study treatment.  The 
type of event, organ system affected, and timing of onset of the event will be factors in assessing 
the likelihood that an AE is related to the study treatment.  Relationship of AEs to study treatment 
will be classified as follows: 
 Not Related:  No relationship exists between the AE and the treatment.  The event is 
attributed to a pre-existing medical condition or an intercurrent event unrelated to the 
study product. 
 Possibly Related:  Follows the treatment but may have developed as a result of an 
underlying clinical condition or treatments/interventions unrelated to the study product. 
 Probably Related:  Follows the treatment but is unlikely to have developed as a result 


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of the subject’s underlying clinical condition or other treatment or other interventions. 
 Definitely Related:  Follows the treatment and physical evidence shows a convincing 
relationship to the treatment. 
 
 
Reporting Requirements for SAEs 
The Investigator is required to report all SAEs.  Once the Investigator becomes aware of an SAE, 
he/she must report the SAE to CellSight within 24 hours at: 
Phone: 650-799-1589 
Email: adverse.events@cellsighttech.com 
 
The CellSight Medical Monitor may request additional supporting documentation as it becomes 
available, such as lab reports, ECG reports, discharge summary, hospital notes, etc.  
The Investigator is also responsible for reporting all SAEs to the appropriate Institutional Review 
Board (IRB) in accordance with local laws and regulations. The Investigator is responsible for 
maintaining documentation in the study file that indicates the IRB has been properly notified. 
Under 21 CFR 312.32(c), the sponsor is required to notify FDA and all participating investigators 
in an IND safety report (i.e., 7- or 15-day expedited report) of potentially serious risks from clinical 
trials or any other source as soon as possible, but no later than 15 calendar days after the sponsor 
receives the safety information and determines that the information qualifies for reporting. 
Participating investigators include all investigators to whom the sponsor is providing drug under 
any of its INDs or under any investigator’s IND (21 CFR 312.32(c)(1)). 
 
 QUALITY CONTROL AND QUALITY ASSURANCE 
 Monitoring Requirements 
In an effort to fulfill the obligations outlined in 21 CFR Part 312 and ICH guidelines which require 
the Sponsor to maintain current personal knowledge of the progress of a study, the Sponsor's 
designated monitor will visit the center(s) during the study as well as maintain frequent telephone 
and written communication. The Investigator will permit the Sponsor to monitor the study as 
frequently as is deemed necessary and provide access to medical records to ensure that data are 
being recorded adequately, that data are verifiable and that protocol adherence is satisfactory.  
The Investigator will permit representatives of the Sponsor and/or designated CRO to inspect all 
CRFs and corresponding study subject original medical records (source documents) at regular 
intervals throughout the study. Subject original medical records and other relevant data must be 
available to support all data recorded in the CRF. In addition to the original medical records, these 
data may include but are not limited to, study, laboratory and diagnostic reports, wound images 
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Site inspections serve to verify strict adherence to the protocol and the accuracy of the data being 
entered on the CRFs, in accordance with federal regulations. A Monitoring Log will be maintained 
at each study site that the monitor will sign, date, and state the type of visit.  
The Investigator should be aware that the study site and subject records may be inspected by the 
Sponsor and or representatives of the designated CRO, FDA, or other regional regulatory 
authority. 
 Acceptability of Case Report Forms  
All CRFs will be completed as soon as possible after the subject's visit. Corrections to data on the 
CRFs will be made according to standard data correction procedures. The Investigator will review 
CRFs to indicate that, to his/her knowledge, they are complete and accurate. CRFs may be 
reviewed by the Sponsor’s or designated CRO’s monitor, who will make a decision as to their 
acceptability.   
 Modification of Protocol 
The Investigator will not modify or alter this protocol without first obtaining the concurrence of 
the Sponsor. Approval by the Investigator’s IRB must also be obtained prior to implementation of 
the change, with two exceptions: 
1. When necessary to eliminate apparent immediate hazard to the subject; or 
2. When the modification does not involve the subject’s participation in the trial. 
An amendment may also require modification of the ICF. The Investigator will provide an 
approval letter for the amendment and revised ICF, if applicable, to the Sponsor. An amendment 
must be in writing and dated by both the Sponsor and the Investigator. If necessary, the Sponsor 
will submit protocol amendments to FDA and other appropriate regulatory authorities. 
 Reporting Protocol Deviations 
The Investigator is obligated to follow the protocol without departure from the requirements 
written in the protocol. If the Investigator deems a deviation from the protocol requirements is 
necessary for a particular subject, the Sponsor will be notified and consulted prior to the subject’s 
continuation in the study. The Sponsor also has the right to discontinue the subject for protocol 
violations. The IRB may also have to be contacted if safety to the subject or if the scientific 
soundness of the study is involved. All protocol deviations must be documented in the CRFs. 
 
Subject Premature Withdrawal from Study 
A subject who is enrolled into the study but does not complete the study will be considered 
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All subjects have the right to withdraw at any point during the study without prejudice. It will be 
documented whether or not each subject completed the clinical study. If, for any subject, study 
treatment or observations were discontinued, the reason(s) will be recorded and the Sponsor should 
be notified promptly. All efforts must be made to collect data and report records and test results as 
completely as possible. Reasons for subject withdrawal/discontinuation may constitute one of the 
following: 
 
• Subject withdrew consent 
• Subject chooses to withdraw from study 
• Subject is withdrawn due to an AE 
• Pregnancy 
• Lost to follow-up  
• The Investigator determines that it is in the subject’s best interest 
• Excessive protocol deviations, as determined by the Investigator  
• Discontinuation of study by the Sponsor 
Important Notes: 
1. 
Subjects may drop out or be withdrawn at their own request. Although subjects do not need 
to give a reason for requesting withdrawal from the trial, the Investigator should make a reasonable 
effort to ascertain the reason(s), while fully respecting the subject's rights. 
2. 
Any subjects reporting Serious Adverse Events (SAEs) that have not resolved by their last 
study visit will be followed to resolution or until 30 days after the subject completes the study. 
3. 
Every attempt should be made to collect follow-up information. The reason for withdrawal 
from the study (if known) will be recorded in the source documents and on the appropriate page 
of the CRF. 
4. 
Before a subject is identified as lost-to-follow-up, the site should make all reasonable 
efforts to contact the subject. These attempts must be documented and should include at a 
minimum one phone call and one follow-up certified letter. 
 
 DATA AND SAFETY MONITORING COMMITTEE 
In addition to the requirements for adverse event reporting as outlined in Section 11.0, this protocol 
is also subject to the UC Davis Cancer Center’s (UCDCC) Data and Safety Monitoring Plan. The 
UCDCC is committed to pursuing high-quality patient-oriented clinical research and has 
established mechanisms to ensure both scientific rigor and patient safety in the conduct of clinical 
research studies. The UCDCC relies on a multi-tiered committee system that reviews and monitors 
all cancer clinical trials and ensures the safety of its participants, in compliance with institutional 


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and federal requirements on adverse event (AE) reporting, verification of data accuracy, and 
adherence to protocol eligibility requirements, treatment guidelines, and related matters. The 
Scientific Review Committee (SRC) assumes overall oversight of cancer studies, with assistance 
and input from two independent, but interacting, committees: the Quality Assurance Committee 
and the Data and Safety Monitoring Committee. A multi-level review system strengthens the 
ability of the UCDCC to fulfill its mission in conducting high quality clinical cancer research. 
According to the UCDCC Data and Safety Monitoring Plan, any new serious adverse events 
related to the drugs being used on this trial are reviewed monthly by the UCDCC Data and Safety 
Monitoring Committee and any applicable changes to the study are recommended to the PI, if 
necessary. 
The UCDCC SRC determines if a UCDCC Data and Safety Monitoring Board (DSMB) is 
required.  If required, the Data and Safety Monitoring Committee will appoint a DSMB. The 
DSMB is responsible for reviewing study accrual logs, adverse event information and dose 
escalation meeting minutes (where applicable) to ensure subject safety and compliance with 
protocol defined guidelines. 
Results of the DSMC audit will be communicated to CellSight, IRB and the appropriate regulatory 
authorities at the time of continuing review, or in an expedited fashion, as needed. 
 
 ETHICAL CONSIDERATIONS AND ADMINISTRATIVE PROCEDURES 
 
Ethics and Good Clinical Practice 
This study must be carried out in compliance with the protocol and Good Clinical Practice, as 
described in:  
1. 
ICH Harmonized Tripartite Guidelines for Good Clinical Practice 1996. 
2. 
Directive 91/507/EEC, The Rules Governing Medicinal Products in the European 
Community. 
3. 
US 21 Code of Federal Regulations dealing with clinical studies (including parts 50 and 
56 concerning informed consent and IRB regulations). 
4. 
Declaration of Helsinki, concerning medical research in humans (Recommendations 
Guiding Physicians in Biomedical Research Involving Human Subjects, Helsinki 1964, 
amended Tokyo 1975, Venice 1983, Hong Kong 1989, Somerset West 1996). 
The investigator agrees, when signing the protocol, to adhere to the instructions and procedures 
described in it and thereby to adhere to the principles of Good Clinical Practice that it conforms 
to. 


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IND Holder Information 
CellSight Technologies is the holder of the IND (IND# 123591).  The company is sponsoring this 
clinical trial and is responsible for the imaging costs incurred in the trial. The radiotracer will be 
manufactured under the direction of CellSight Technologies at a qualified production site. 
 
Institutional Review Board/Independent Ethics Committee 
Before implementing this study, the protocol, the proposed informed consent form and other 
information to subjects, must be reviewed by a properly constituted Institutional Review Board 
Committee (IRB). A signed and dated statement that the protocol and informed consent have been 
approved by the IRB must be given to Cellsight before study initiation. Any amendments to the 
protocol, other than administrative ones, must be approved by this committee. 
 
Informed Consent 
The investigator must explain to each subject (or legally authorized representative) the nature of 
the study, its purpose, the procedures involved, the expected duration, the potential risks and 
benefits involved and any discomfort it may entail. Each subject must be informed that 
participation in the study is voluntary and that he/she may withdraw from the study at any time 
and that withdrawal of consent will not affect his/her subsequent medical treatment or relationship 
with the treating physician. 
This informed consent should be given by means of a standard written statement, written in non-
technical language. The subject should read and consider the statement before signing and dating 
it and should be given a copy of the signed document. If the subject cannot read or sign the 
documents, oral presentation may be made or signature given by the subject’s legally appointed 
representative, if witnessed by a person not involved in the study, mentioning that the patient could 
not read or sign the documents. No patient can enter the study before his/her informed consent has 
been obtained. 
The method of obtaining and documenting the informed consent and the contents of the consent 
will comply with ICH-GCP and all applicable regulatory requirement(s).  In accordance with UCD 
policy an original signed and dated participant Informed Consent document will reside in a secured 
location within the department of radiology. Copies of the signed and dated Informed Consent 
document will be provided to the study participant and UCD Health System Information 
Management for inclusion in the participant’s UCD Health System Medical Record. 
The informed consent form is considered to be part of the protocol and must be submitted by the 
investigator with it for IRB/IEC/REB approval.  
Women of child bearing potential should be informed that taking the study drug may involve 
unknown risks to the fetus if pregnancy were to occur during the study and agree that in order to 
participate in the study they must adhere to the contraception requirement for the duration of the 


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study. If there is any question that the patient will not reliably comply, they should not be entered 
in the study. 
 
Sharing of Results with Subjects 
The results of this research will not be shared with subjects. However, results may be shared as 
described in Section 7.1.1. 
 
Disclosure and Confidentiality 
☒ I understand that if this study involves the use of  the UC Davis Health Electronic Health Record 
(EMR/EPIC) it also contains the clinical data for Marshall Medical Center (MMC). I understand 
that MMC patient data cannot be accessed for research purposes and that I must take the necessary 
steps to ensure that MMC data is not accessed, used, or disclosed for UC Davis Health research 
purposes. 
In order to maintain patient privacy, all study reports and communications will identify the patient 
by initials and the assigned patient number.  Data capture records and drug accountability records 
will be stored in secure cabinets in the department of radiology. Medical records of patients will 
be maintained in strict confidence according to legal requirements.  The patient’s confidentiality 
will be maintained and will not be made publicly available to the extent permitted by the applicable 
laws and regulations. 
Participant confidentiality is strictly held in trust by the participating investigators, their staff, and 
the sponsor(s) and their agents. This confidentiality is extended to cover testing of biological 
samples and genetic tests in addition to the clinical information relating to participants. Therefore, 
the study protocol, documentation, data, and all other information generated will be held in strict 
confidence. No information concerning the study or the data will be released to any unauthorized 
third party without prior written approval of the sponsor. 
The study monitor, other authorized representatives of the sponsor, representatives of the IRB or 
pharmaceutical company supplying study product may inspect all documents and records required 
to be maintained by the investigator, including but not limited to, medical records (office, clinic, 
or hospital) and pharmacy records for the participants in this study. The clinical study site will 
permit access to such records.  
The study participant’s contact information will be securely stored at the clinical site for internal 
use during the study. At the end of the study, all records will continue to be kept in a secure location 
for as long a period as dictated by local IRB and Institutional regulations.  
Study participant research data, which is for purposes of statistical analysis and scientific reporting, 
will be stored according to IRB approved specifications, and will be transmitted to the Sponsor. 
This will not include the participant’s contact or identifying information. Rather, individual 
participants and their research data will be identified by a unique study identification number. The 
study data entry and study management systems used by clinical sites and by Sponsor research 


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staff will be secured and password protected. At the end of the study, all study databases will be 
de-identified and archived as per IRB approved specifications. 
 
Declaration of Helsinki 
The investigator must conduct the trial in accordance with the principles of the Declaration of 
Helsinki. Copies of the Declaration of Helsinki and amendments will be provided upon request or 
can 
be 
accessed 
via 
the 
website 
of 
the 
World 
Medical 
Association 
at 
http://www.wma.net/e/policy/17-c_e.html. 
 
Compensation for Research-Related Injury 
If a subject is injured as a result of being in this study, the University of California will provide 
necessary medical treatment.  Depending on the circumstances, the costs of the treatment may be 
covered by the University or the study sponsor or may be billed to the subject’s insurance company 
just like other medical costs.  The University and the study sponsor do not normally provide any 
other form of compensation for injury. 
 
Economic Burden to Subjects 
All study-related procedures will be paid by the study and not charged to the subject.  
 
 
 
 


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 REFERENCES 
1. Brinkman, J.A., Fausch, S.C, Weber, J. S., Kast, W. M. (2004) Peptide-based vaccines for 
cancer immunotherapy, Expert Opinion on Biological Therapy, 4:2, 181-198, DOI: 
10.1517/14712598.4.2.181 
2. Castaldi, P., et al., Role of F-18-FDG PET-CT in head and neck squamous cell carcinoma. 
Acta Otorhinolaryngologica Italica, 2013. 33(1): p. 1-8. 
3. Chan, I. T., Limmer, A., Louie, M. C., Bullock, E. D., Fung-Leung, W. P., Mak, T. W., & 
Loh, D. Y. (1993). Thymic selection of cytotoxic T cells independent of CD8 alpha-Lck 
association. Science, 261(5128), 1581-1584.  
4. Dal Bello, M.G., et al., Understanding the checkpoint blockade in lung cancer 
immunotherapy. Drug Discov Today, 2017. 22(8): p. 1266-1273. 
5. Dallal, R.M. and M.T. Lotze, The dendritic cell and human cancer vaccines. Current Opinion 
in Immunology, 2000. 12(5): p. 583-8. 
6. Davis, M.M., et al., Dynamics of cell surface molecules during T cell recognition. Annu Rev 
Biochem, 2003. 72: p. 717-42. 
7. DeAngelo, D. J. (2009). Nelarabine for the Treatment of Patients with Relapsed or Refractory 
T-cell Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma, Hematology/Oncology 
Clinics of North America, 
11. Volume 23, Issue 5,2009,Pages 1121-1135, https://doi.org/10.1016/j.hoc.2009.07.008. 
8. Eisenhauer, E. A., Therasse, P., Bogaerts, J., Schwartz, L. H., Sargent, D., Ford, R., Verweij, 
J. (2009). New response evaluation criteria in solid tumours: revised RECIST guideline (version 
1.1). Eur J Cancer, 45(2), 228-247. doi:10.1016/j.ejca.2008.10.026 
9. Franc BL, Goth S, MacKenzie J, et al. In Vivo PET Imaging of the Activated Immune 
Environment in a Small Animal Model of Inflammatory Arthritis. Mol Imaging. 
2017;16:1536012117712638. doi:10.1177/1536012117712638 
10. Fox CJ, Hammerman PS, Thompson CB. Fuel feeds function: energy metabolism and the T-
cell response. Nat Rev Immunol. 2005 Nov;5(11):844-52. Review. doi: 10.1038/nri1710 
11. Gilardi, L., et al., Ipilimumab-Induced Immunomediated Adverse Events: Possible Pitfalls in 
18F -FDG PET/CT Interpretation. Clinical nuclear medicine, 2014. 39(5): p. 472-4. 
12. Hodi, F. S., O'Day, S. J., McDermott, D. F., Weber, R. W., Sosman, J. A., Haanen, J. B., 
Urba, W. J. (2010). Improved survival with ipilimumab in patients with metastatic melanoma. N 
Engl J Med, 363(8), 711-723. doi:10.1056/NEJMoa1003466 
13. Kantoff, P.W., et al., Sipuleucel-T Immunotherapy for Castration-Resistant Prostate Cancer. 
New England Journal of Medicine, 2010. 363(5): p. 411-422. 
14. Levi J, Lam T, Goth SR, et al. Imaging of Activated T Cells as an Early Predictor of Immune 
Response to Anti-PD-1 Therapy. Cancer Res. 2019;79(13):3455–3465. doi:10.1158/0008-
5472.CAN-19-0267 
15. Mayordomo, J.I., et al., Bone marrow-derived dendritic cells pulsed with synthetic tumour 
peptides elicit protective and therapeutic antitumour immunity. Nat Med, 1995. 1(12): p. 1297-
302. 
16. Mayordomo, J.I., et al., Therapy of murine tumors with p53 wild-type and mutant sequence 
peptide-based vaccines. J Exp Med, 1996. 183(4): p. 1357-65. 
 


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17. Nair-Gill E, Wiltzius SM, Wei XX, et al. PET probes for distinct metabolic pathways have 
different cell specificities during immune responses in mice [published correction appears in J 
Clin Invest. 2010 Jul 1;120(7):2641]. J Clin Invest. 2010;120(6):2005–2015. 
doi:10.1172/JCI41250 
18. Namavari, M., Chang, Y., Kusler, B. et al. Synthesis of 2?-Deoxy-2?-[ 18F]Fluoro-9-?-D-
Arabinofuranosylguanine: a Novel Agent for Imaging T-Cell Activation with PET. Mol Imaging 
Biol 13, 812–818 (2011). https://doi.org/10.1007/s11307-010-0414-x 
19. Nishino, M., et al., Developing a Common Language for Tumor Response to 
Immunotherapy: Immune-Related Response Criteria Using Unidimensional Measurements. 
Clinical Cancer Research, 2013. 19(14): p. 3936- 3943. 
20. Novellino, L., C. Castelli, and G. Parmiani, A listing of human tumor antigens recognized by 
T cells: March 2004 update. Cancer Immunol Immunother, 2005. 54(3): p. 187-207 
https://doi.org/10.1007/s00262-004-0560-6 
21. Radu CG, Shu CJ, Nair-Gill E, et al. Molecular imaging of lymphoid organs and immune 
activation by positron emission tomography with a new [18F ]-labeled 2'-deoxycytidine analog. 
Nat Med. 2008;14(7):783–788. doi:10.1038/nm1724 
22. Ribas, A. and J.D. Wolchok, Cancer immunotherapy using checkpoint blockade. Science, 
2018. 359(6382): p. 1350-1355. 
23. Ronald, J.A., et al., A PET Imaging Strategy to Visualize Activated T Cells in Acute Graft-
versus- Host Disease Elicited by Allogenic Hematopoietic Cell Transplant. Cancer Res, 2017. 
77(11): p. 2893-2902. doi: 10.1158/0008-5472.CAN-16-2953 
24. Soler, C., Garcia-manteiga, J., Valdes, R., Xaus, J., Comalada, M., Casado, F.J., Pastor-
Anglada, M., Celada, A. and Felipe, A. (2001), Macrophages require different nucleoside 
transport systems for proliferation and activation. The FASEB Journal, 15: 1979-1988. 
doi:10.1096/fj.01-0022com 
25. Wolchok, J. D., Hoos, A., O'Day, S., Weber, J. S., Hamid, O., Lebbe, C., Hodi, F. S. (2009). 
Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related 
response criteria. Clin Cancer Res, 15(23), 7412-7420. doi:10.1158/1078-0432.ccr-09-1624 
 
 
 
 
 
 
 
 
 
 
 


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 APPENDICES 
Appendix 1: ECOG and Karnofsky Performance Status Scores1,2  
 
ECOG PERFORMANCE STATUS 
KARNOFSKY PERFORMANCE STATUS 
0—Fully active, able to carry on all pre-disease 
performance without restriction 
100—Normal, no complaints; no evidence of disease 
 90—Able to carry on normal activity; minor signs or 
symptoms of disease 
1—Restricted in physically strenuous activity but 
ambulatory and able to carry out work of a 
light or sedentary nature, e.g., light house 
work, office work 
 80—Normal activity with effort, some signs or 
symptoms of disease 
 70—Cares for self but unable to carry on normal 
activity or to do active work 
2—Ambulatory and capable of all selfcare but 
unable to carry out any work activities; up 
and about more than 50% of waking hours 
 60—Requires occasional assistance but is able to care 
for most of personal needs 
 50—Requires considerable assistance and frequent 
medical care 
3—Capable of only limited selfcare; confined to 
bed or chair more than 50% of waking hours 
 40—Disabled; requires special care and assistance 
 30—Severely disabled; hospitalization is indicated 
although death not imminent 
4—Completely disabled; cannot carry on any 
selfcare; totally confined to bed or chair 
 20—Very ill; hospitalization and active supportive 
care necessary 
 10—Moribund 
5—Dead 
  0—Dead 
1. Karnofsky D, Burchenal J, The clinical evaluation of chemotherapeutic agents in cancer. In: MacLeod C, ed. 
Evaluation of Chemotherapeutic Agents. New York, NY: Columbia University Press; 1949:191–205. 
2. Zubrod C, et al. Appraisal of methods for the study of chemotherapy in man: Comparative therapeutic trial of 
nitrogen mustard and thiophosphoramide. Journal of Chronic Diseases; 1960:11:7-33. 
 
 
 
 
 


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Appendix 2: Study Registration and Participant visits 
A. The subject will sign and date the Informed Consent Form (ICF), and Health Insurance 
Portability and Accountability Act (HIPAA) authorization (according to site’s practices) prior 
to any study-related procedures with the exception of the standard-of-care (SOC) 
diagnostic/tumor staging CT or MRI that would be accepted for imaging review to assess 
eligibility of NSCLC subjects, if done within 45 days prior to Visit 2.  
B. Once signed, informed consent has been obtained; patients will be entered on study.  To 
register a patient, the study coordinator must complete the Eligibility Checklist.  The study 
coordinator will register the patient onto the study and assign a unique an Enrollment ID before 
initiation of the study drug administration.   
C. Pre-study laboratory tests must be completed prior to registration within the time frame 
specified in the protocol.   
D. A subject failing to meet all protocol requirements may not be registered.  If you have any 
questions regarding eligibility, please contact the coordinating site PI or Study Coordinator 
E. Unscheduled visits may be required in addition to the scheduled visits per the Investigator’s 
discretion. The details of these unscheduled visits with subjects will be recorded in the medical 
records and on the Case Report Form (CRF). 
F. If a subject misses a visit, the site is to make every effort to have the subject return as soon as 
possible to make up the visit. Once the subject is seen, he/she is to return to his/her original 
visit schedule. 
G. A subject who has signed the consent form but does not receive any [18F]F-AraG infusion is 
classified as a screen failure. Subject number, demographic information, and reason for screen 
failure will be collected. 
H. A subject who is classified as a screen failure will be replaced. A subject who does not receive 
at least one infusion of [18F]F-AraG and the associated PET/CT scans will also be replaced. 
 
 

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Title of research study: A Pilot Study of [18F]F-ARAG Pharmacokinetics in Tumors and Non-
Malignant Tissue using Dynamic Total Body PET Imaging in Healthy Subjects and in Patients with 
Non-Small Cell Lung Cancer (NSCLC) 
Investigator: Simon R. Cherry, Ph.D., Professor of Biomedical Engineering and Radiology; Megan 
Daly, MD, Associate Professor, UC Davis Department of Radiation Oncology
California Experimental Subjects Bill of Rights 

Someone will explain this research study to you, including:
o
The nature and purpose of the research study.
o
The procedures to be followed.
o
Any drug or device to be used. 

Any common or important discomforts and risks.

Any benefits you might expect.

Whether or not you take part is up to you.

You can choose without force, fraud, deceit, duress, coercion, or undue influence.

You can choose not to take part.

You can agree to take part now and later change your mind.

Whatever you decide it will not be held against you.

You can ask all the questions you want before you decide.

If you agree to take part, you will be given a signed and dated copy of this document. 
Key Information about This Research Study
You are invited to participate in a research study. The purpose of this research is to see how a new drug, 
called a “radiotracer”, enters and leaves the blood and tissues over time.  This radiotracer attaches to 
immune cells and shines a light that can be seen using a special camera called a Positron Emission 
Tomography Scanner (PET Scanner). You are invited to be in this study because you are either a healthy 
participant or you are a participant that has been diagnosed with Non-Small Cell Lung Cancer (NSCLC) 
and will be starting treatment with a type of therapy called immunotherapy. Your participation in this 
research will involve 3 visits if you are a healthy participant and will last about 4-5 hours.  If you are a 
participant with NSCLC, your participation will involve 4-5 visits (depending on your preference) and 
will last about 5-7 hours.  We expect up to 8 people (2-4 with NSCLC and 2-4 healthy participants) at 
UC Davis will join and participate in this research.
Participation in this study will involve getting a PET/CT Scan using a total-body PET/CT scanner called 
the EXPLORER.  The total-body PET/CT scanner is the first FDA-cleared medical scanner to be able to 
scan the entire human body all at the same time.  If you are a healthy participant, you will get one PET 
scan and will be asked about your health 7 days after the scan.  If you have a diagnosis of NSCLC, you 
will get one PET scan before you start immunotherapy and you will have the option to get a second PET 
scan after starting immunotherapy. Participants with NSCLC will also be asked about their health 7 days 
after their last scan.  All research studies involve some risk.  These risks are described in detail later in 
this document. There is not the possibility that you may benefit from participation in this study. 
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Here are some reasons you may not want to participate in this research: the research study visits could 
last up to 5 hours for healthy participants and up to 7 hours for those diagnosed with NSCLC.  For some 
people, lying inside the scanners may cause fear or anxiety due to the confined space.  Also, the scan 
may reveal suspicious findings and/or findings of unclear cause which may need further follow-up 
procedures.  Medical follow-up may include doctor’s visits, more scans or surgery, and may expose you 
to additional risks from the follow-up procedures.  
Your participation in this study is voluntary. You do not have to participate in this study if you do not 
want to. There may be other choices available to you. You will not lose any services, benefits, or rights 
you would normally have if you choose not to participate. 
The remainder of this form contains a more complete description of this study. Please read this 
description carefully. You can ask any questions you need to help decide whether or not to join this 
study. 
Information to help you understand research is online at 
http://www.research.ucdavis.edu/policiescompliance/irb-admin/for-research-participants. 
What if I have Questions? 
The persons in charge of this study are Simon R. Cherry, Ph.D. and Megan Daly, MD. If you have 
questions or concerns about this study, please contact the Lead Researchers by reaching out to the 
Clinical Research Coordinator at 916-731-9004.
For non-emergency issues you can call the UCDMC Hospital Operator (916-734-2011), tell the 
Operator you are participating in a research study and you wish to talk to the Nuclear Medicine 
Radiologist on duty. In the case of an emergency, dial 911 from any phone.
If you have any questions about your rights as a research subject or have complaints about the research 
study or study team, you may talk to a team member at the Institutional Review Board (IRB) at (916) 
703-9151, hs-irbadmin@ucdavis.edu, or 2921 Stockton Blvd, Suite 1400, Room 1429, Sacramento, CA 
95817. The IRB is a group of people who oversee research. 
How is this research funded? 
This research is being funded by CellSight Technologies, Inc., also called the sponsor. Sponsors may 
change or be added.
UC Davis is being paid to conduct this study, but the study doctor and research staff have not received 
any direct income from the sponsor.
The University of California has a financial interest in this study. The University receives both research 
funding and a share of the revenues based on sales of the device being used in this study.
What happens if I say yes, I want to be in this research?
If you decide to participate in this research study, the researchers will ask you to come into the 
EXPLORER Molecular Imaging Center (located at 3195 Folsom Blvd in Sacramento, California) where 
the total-body PET/CT Scanner is located.
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If you are a healthy participant, you will have up to 3 research study visits:

First Visit 
o
A member of the research team will meet you to explain the study in detail and answer 
any questions you may have
o
If you agree to take part in this research study, the researcher will ask you to sign a 
consent form to participate
o
The researchers will also ask you to sign a HIPAA Authorization for Research form 
because we will be collecting and reviewing personal information, including your present 
and past medical records
o
The researchers will collect medical information about you, including history of COVID-
19 vaccination, vital signs, height, and weight.  They will also collect demographics 
information.  
o
The researchers will schedule your appointment for the PET Scan

Second Visit 
o
Women 18-60 years old will be required to have a pregnancy test prior to any scans, 
unless documented hysterectomy or bilateral ovarian removal is available 
o
The researchers will ask you about any health issues or symptoms you may be having
o
The researchers will also ask you about any new or current medications you may be 
taking
o
You will undergo a PET scan as described below

Third Visit 
o
This visit can be done on the phone and will take place 7 days after your PET scan
o
The researchers will ask you about any health issues or symptoms you might have 
experienced since the PET scan
If you are an individual diagnosed with NSCLC, you will have up to 4 separate study visits:

First Visit
o
A member of the research team will meet you to explain the study in detail and answer 
any questions you may have
o
If you agree to take part in this research study, the researcher will ask you to sign a 
consent form to participate
o
The researchers will also ask you to sign a HIPAA Authorization for Research form 
because we will be collecting and reviewing personal information, including your present 
and past medical records
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o
The researchers will collect medical information about you, including history of COVID-
19 vaccination, vital signs, height, and weight.  They will also collect demographics 
information.  
o
The researchers will also ask you about any new or current medications you may be 
taking
o
The researchers will schedule your appointment for the PET Scan

Second Visit (This visit and the First Visit can take place on the same day if that is more 
convenient for you)
o
Women  18-60 years old will be required to have a pregnancy test prior to any scans, 
unless documented hysterectomy or bilateral ovarian removal is available
o
The researchers will ask you about any health issues or symptoms you may be having
o
The researchers will also ask you about any new or current medications you may be 
taking
o
You will undergo a PET scan within 7 days of starting immunotherapy; the PET scan is 
described below

Third Visit (Not a Research Visit)
o
As agreed upon by you and your oncologist, you will start immunotherapy within one 
week of your total-body PET Scan

Fourth Visit 
o
This visit can be done on the phone and will take place 7 days after your last PET scan
o
The researchers will ask you about any health issues or symptoms you might have 
experienced since the PET scan
Total-Body PET/CT Scan (for all participants)

A Nuclear Medicine Technologist will ask you some questions to make sure everything is OK 
for the PET Scan

You will be asked to remove your clothing and wear a hospital gown that we will provide

Prior to entering the scan room, you will be asked to use the restroom

You will be positioned on your back on the scanner table with cushions to make you comfortable

You will have an IV needle placed into a vein for injection of the radiotracer

You will undergo a low-dose CT scan for about 30 seconds while lying on the scanner table 

The Nuclear Medicine Technologist will inject you with the radiotracer using the IV needle

You will undergo a PET scan for 90 minutes

After the 90-minute scan, the IV line will be removed
If you are unable to lay down on the scanner table for 90 minutes, the scan procedure will be 
modified like this:

After injection of the radiotracer, you will undergo a PET scan for 60 minutes
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
After the 60-minute scan, the IV line will be removed

You can then get off the scanner table, stretch, or use the restroom

80 minutes after the radiotracer injection, you will be asked to position yourself once again 
on the scanner table

You will undergo an ultra-low-dose CT scan for about 30 seconds while lying on the scanner 
table

You will then undergo a 10-minute PET scan
How is being in this study different from my regular health care?
If you take part in this study, the main difference between your regular care and the study is that your 
regular health care does not involve the PET/CT scans that are part of this study.
Do I have to be in this study? What if I say “yes” now and change my mind later?
No, you do not have to be in this study. Taking part in research is voluntary. You can choose to be in the 
study or not be in the study. If you decide to be in the study, you can choose to leave the study at any 
time.
If you decide not to take part in the study, or if you choose to leave the study, your choice will not affect 
any treatment relationship you have with healthcare providers at UC Davis Health or any services you 
receive from them. No matter what you decide, and even if your decision changes, there will be no 
penalty to you. You will not lose medical care or any legal rights.
Please let the researchers know if you choose to leave the study. 
If you choose to leave the study, data that have already been collected will not be removed from the 
study database.
Can I be removed from the research without my OK?
The researchers may take you out of the study, even if you want to continue, if:

you do not follow the study rules or you no longer meet the requirements to be in the study

the researchers feel it is in your best interest to discontinue participation. Such circumstance may 
include unanticipated discomfort and/or fatigue from laying on the scanner table, and feelings of 
claustrophobia from being inside the scanner bore; or

the study is stopped by the sponsor or researchers.
Is there anyway being in this study could be bad for me?
There are risks to participating in this research.  The study doctor and study team will monitor you to see 
if you are experiencing any harm related to your participation.  If you experience any pain or discomfort, 
you must inform the study team as soon as possible.  
Injection Risks: bruising or infection at the site of the injection
Radiation Risks: This study involves a radiation exposure that is typical of other diagnostic tests using 
ionizing radiation. The amount of radiation exposure received in this study is below the levels that are 
thought to result in a significant risk of harmful effects.
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To minimize radiation exposure to your bladder, you should drink at least an 8 oz glass of water before 
injection with the radiotracer and after your PET/CT scans. To help protect yourself and others, you 
should flush the toilet several times after each use for 12 hours after injection with the radiotracer. You 
should also wash your hands after each use of the bathroom. If your blood, urine, or feces comes in 
contact with your clothing, you should wash them separately than other clothes.
Scan Risks: Due to the (up to) 90-minute long scan time, you may feel discomfort and/or fatigue from 
laying on the scanner table.  You may also experience claustrophobia from being inside the scanner 
because it is a partially enclosed space.
There is the possibility that the scan will reveal some suspicious findings or findings of unknown cause 
requiring further medical follow-up.  This medical follow-up may include doctor’s visits, more scans or 
surgery, with all the potential risks associated with these procedures.  These risks may vary from minor 
risks to serious risks such as death or permanent disabilities.  
Privacy Risks: As with all research, there is a chance that confidentiality could be compromised. To 
minimize the risks of breach of confidentiality, we will not include any information that directly 
identifies you on the specimens and information we collect, and on the data resulting from the research. 
What about Birth Control? 
Contraception Requirements for Women 
The study involves radiation that may harm a fetus or a breastfeeding baby. If you are pregnant or 
breastfeeding, you cannot take part in this study. If you think you may be pregnant, you should not 
volunteer for this study. If you are able to become pregnant, you must have a pregnancy test before you 
begin the study and while you are in the study. You must not get pregnant or breastfeed while you are in 
this study. If you are a woman who can become pregnant, you must take measures to avoid becoming 
pregnant while you are in this study. The following are acceptable measures to avoid becoming 
pregnant:
One of the following forms of birth control should be used: 

Abstinence (not having sexual relations with a person of the opposite sex)

Implantable hormone 

Intrauterine Device 

Male partner must have a vasectomy

Female sterilization 

Hormonal injection 

Oral contraceptives 
 
Will being in this study help me in any way?
Being in this study will not help you directly. But your participation in the study may benefit other 
people in the future by helping us learn more about how the radiotracer can be used in the future when 
performing scans. This study is not a substitute for your regular medical care. You should continue to 
see your regular medical providers.
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Will being in this study cost me anything?
There will be no cost to you for the total-body PET/CT scans and visits that are done for research 
purposes only and are not part of your regular care.  If you are a participant with NSCLC: You or 
your insurance will be billed for your regular treatment involving immunotherapy.
You will have to pay for basic expenses like any childcare, food, parking, or transportation related to 
study activities. 
If you need treatment for side effects while you are on the study, you or your insurance will need to pay 
for this treatment. 
For more information about possible costs, please contact the research team. The research team can 
follow UC Davis Uninsured Non-Emergency Estimate Policy (Policy ID 1883) to work with their 
department and Decision Support Services to get you a cost estimate.
Will I be paid or receive anything for being in this study?
We will pay you $100 for each PET/CT research scan you undergo.  Payment will be provided at the 
end of your scan visit in the form of gift cards.  If you are a participant with NSCLC that volunteered to 
undergo the second optional scan as described in the “Are there any optional parts of the study?” section 
below will receive a maximum total of $200.
What happens if I am injured or get sick because of this study?
If you are injured or get sick because of this study, medical care is available to you through UC Davis 
Health, your local provider, or emergency services. 

If it is an emergency, call 911 right away or go to the emergency room. 

For non-emergency issues, you can call the UC Davis Health Hospital Operator (916-734-2011), 
tell the Operator you are participating in a research study and you wish to talk to Nuclear 
Medicine Radiologist on call.
If you are injured as a result of being in this study, the University of California will provide the 
necessary medical treatment. Depending on the circumstances, the costs of the treatment may be covered 
by the University or the study sponsor or may be billed to your insurance company just like other 
medical costs. The University and the study sponsor do not normally provide any other form of 
compensation for injury. For more information about compensation, you may contact the IRB 
Administration at (916) 703-9151 or  HS-IRBAdmin@ucdavis.edu.
What happens to the information collected for the research?
We will do our best to limit the use or disclosure of your personal information, including information 
from this research study and from your medical records, to people who have a need to review this 
information. We cannot promise complete confidentiality. Some organizations may be required to 
inspect and copy your information including the IRB and other University of California representatives 
responsible for the management or oversight of this study.
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We have strict rules to protect your personal information and protected health information (PHI). We 
will limit who has access to your name, address, phone number, and other information that can identify 
you. We will remove identifiable information from the data we collect about you. After we remove all of 
the identifiers, we will place a code on the information. The code will be linked to your identity but the 
link will be kept in a location that is separate from your study data. We will maintain your study data on 
encrypted computers and access to the information will be limited to only members of the research team 
who need the access to properly conduct the study. The information we send to the sponsor will not 
include information that directly identifies you.  Instead, a code will be applied to the data and link 
between the code and your identity will be kept at the research site. 
 However, we cannot promise complete confidentiality. If you agree to be in this study, Federal or state 
laws may permit or require us to show information to university or government officials and to study 
sponsors responsible for monitoring this study. We may also show your medical records to study 
monitors, auditors, the IRB, and the FDA. These groups are obligated to maintain your confidentiality. 
The following is a list of individuals who may access your records:  

Members of the research team 

Offices and committees responsible for the oversight of research

Personnel who schedule or perform medical tests or procedures, handle accounting and billing, 
or do other tasks related to this study

The study sponsor, CellSight
If you agree to participate in this research study, a signed copy of this consent document and the privacy 
authorization form may be filed in your electronic medical record (EMR) and your study participation 
may be added to your EMR. This information will be used for your care and treatment and for 
healthcare operations, which may include billing and payment. Federal and state privacy laws give 
patients the right to access information about their care and treatment contained in their medical record. 
During this study, you may not be able to access certain information related to this study in your EMR 
until the study is complete to ensure that the study remains unbiased.  If necessary for your care, this 
information will be provided to you or your physician. We will access protected health information (e.g., 
your medical record) for this study and you will be asked to sign a separate form, commonly referred to 
as a HIPAA authorization, to give your permission. Your medical records may become part of the 
research record.  If that happens, your medical records may be looked at by the sponsor of this study and 
government agencies or other groups associated with the study.  They may not copy or take your 
personal health information from your medical records unless permitted or required by law.
Federal law provides additional protections of your medical records and related health information. 
These are described in the UC Davis Health System Notice of Privacy Practices 
(http://www.ucdmc.ucdavis.edu/legal/privacy/) and in an attached document.
Will I receive any results from this research? 
We will create radiation dose reports from your PET/CT scans and we will give you a copy if you ask 
for it.  The results of this research will not be shared with you.  However, you and your primary care 
doctor will be notified if any incidental findings are detected as described below.  
It is possible the total-body PET/CT scans may detect false positive findings that may require further 
follow-up (clinical, imaging or surgical) with all the risks associated with these follow-up procedures.  
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The PET/CT images created for this study are for research and are not meant to judge the level of your 
health, as they would be if they were part of your medical care.  The images will not receive the usual 
clinical review by radiologists who interpret PET/CT scans. This means that some findings may be 
overlooked or misinterpreted.  However, if a member of the study team, while reviewing your images, 
notices any findings they will share this with the Study Radiologist.  If the Study Radiologist thinks a 
medical problem might be present, we will contact you within 8 weeks to discuss the possible medical 
problems or immediately if it appears urgent to the Study Radiologist.  If you request it in writing, we 
can provide you with a copy of a section of your CT and PET images to take to a doctor you designate.  
We may not be able to share any images from the PET portion of your scan if they are difficult to 
interpret or if we are restricted by the sponsor of the study.  We will send a letter upon your request to a 
doctor you designate letting them know that you are enrolled in this study and that it included getting a 
PET/CT scan for research.  The letter will also state that the images did not receive the usual clinical 
review but that findings related to a possible medical problem were seen by a UC Davis radiologist.  
Your doctor can contact the Study Doctor at any time to discuss your PET/CT scan.  
Are there any optional parts of the study? 
This part of the consent form is about an additional optional part of the study that only participants 
diagnosed with NSCLC can choose to take part in. Things to know about the optional part of the study:

It is optional. You can still take part in the main study even if you say “no” to this part of the 
study.

This part of the study will not help you directly. We hope the results from the optional part of the 
study will help us learn more about how the radiotracer can be used in the future when 
performing scans with cancer patients.   

We will not tell you the results of the optional part of the study, and we will not put the results in 
your medical records. 

Taking part in the optional part of the study will not cost you anything. You will have to pay for 
basic expenses like any childcare, food, parking, or transportation needed for the optional study 
visit. 

Initial your choice of “yes” or “no” for the optional part of the study.
If you are willing, we would like to schedule a second total-body PET/CT scan to take place 7 to 14 
days after your first immunotherapy treatment.  
o
Women of childbearing potential will be required to have a pregnancy test prior to any scan
o
The researchers will ask you about any health issues or symptoms you may be having
o
The researchers will also ask you about any new or current medications you may be taking
o
You will undergo a PET/CT scan as described above
Seven days after this scan, the researchers will ask you about any health issues or symptoms you might 
have experienced since the PET scan. 
Are you willing to participate in this optional part of the study and undergo a second PET/CT scan?
_____ YES
_____ NO
Protocol Version Date: 04/23/2024
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May we contact you by e-mail? 
We are requesting your email address so we can communicate with you for any matter related to this 
study including your scheduled visits. Email is generally not a secure way to communicate about your 
health, as there are many ways for unauthorized users to access email. You should avoid sending 
sensitive, detailed personal information by email. Email should also not be used to convey information 
of an urgent nature. If you need to talk to someone immediately, please contact the Study Coordinator at 
916-731-9004. You do not have to provide your email address to participate in this study. Please initial 
one of the lines below.
_____  Yes, you may use email to contact me for this study. 
My email address is: _____________________
_____  No, I do not want to be contacted by email. 
Protocol Version Date: 04/23/2024
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Signature Block for Capable Adult
Your signature documents your permission to take part in this research.
Signature of subject
Date
Printed name of subject
Signature of person obtaining consent
Date
Printed name of person obtaining consent
My signature below documents that the information in the consent document and any other written 
information was accurately explained to, and apparently understood by, the subject, and that consent 
was freely given by the subject.
Signature of witness to consent process
Date
Printed name of person witnessing consent process
Protocol Version Date: 04/23/2024
ICF Version Date: 04/23/2024
 
 
APPROVED by the Institutional Review
Board at the University of California, Davis
 
Protocol
APPROVED
 
1630355
April 26, 2024