Theranostics of Radiolabeled Somatostatin Antagonists 68Ga-DOTA-JR11 and 177Lu-DOTA-JR11 in Patients With Neuroendocrine Tumors
Phase: NA
Conditions: Neuroendocrine Tumors
Sponsor: Memorial Sloan Kettering Cancer Center

Memorial Sloan Kettering Cancer Center 
IRB Number: 15-161 A(7) 
Approval date: 09-Sep-2020 
Page 1 of 39 
 
 
 
 
 
 
 
Theranostics of Radiolabeled Somatostatin Antagonists 68Ga-DOTA-JR11 and 
177Lu-DOTA-JR11 in Patients with Neuroendocrine Tumors 
 
PROTOCOL FACE PAGE FOR 
MSKCC THERAPEUTIC/DIAGNOSTIC   PROTOCOL 
 
Principal Investigator/Department: 
Lisa Bodei, MD 
Radiology/Molecular  Imaging 
and Therapy Service (MITS) 
Co-Principal 
Investigator(s)/Department: 
Diane Reidy-Lagunes, MD 
Neeta Pandit-Taskar, MD 
Joseph O’Donoghue, PhD 
Medicine/ Solid Tumor 
Service, GI Oncology (GI) 
Radiology/MITS 
Medical Physics 
Investigator(s)/Department: 
Jorge A. Carrasquillo, MD 
Ryan Reddy, MD 
John Humm, PhD 
Ghassan Abou-Alfa, MD 
Andrea Cercek, MD 
Andrew Epstein, MD 
James Harding, MD 
David Ilson, MD, PhD 
Yelena Janjigian, MD 
David Kelsen, MD 
Nancy Kemeny, MD 
Geoffrey Ku, MD 
Eileen O’Reilly, MD 
Leonard Saltz, MD 
Neil Segal, MD, PhD 
Armin Shahrokni, MD 
Zsofia Stadler, MD 
Anna Varghese, MD 
Rona Yaeger, MD 
Kenneth Yu, MD 
Carlos Flombaum, MD 
Jason Lewis, PhD 
Serge Lyashchenko, Pharm D 
Simone Krebs, MD 
Mithat Gonen, PhD 
Laure Michaud, MD 
Romina Giancipoli, MD 
Radiology/MITS 
Radiology 
Medical Physics 
Medicine/GI 
Medicine/GI 
Medicine/GI 
Medicine/GI 
Medicine/GI 
Medicine/GI 
Medicine/GI 
Medicine/GI 
Medicine/GI 
Medicine/GI 
Medicine/GI 
Medicine/GI 
Medicine/GI 
Medicine/GI 
Medicine/GI 
Medicine/GI 
Medicine/GI 
General  Medicine/Nephrology 
Service 
Radiochemistry and Imaging 
Sciences Service 
Radiochemistry and Imaging 
Sciences Service 
Radiology/MITS 
Biostatistics 
SKI 
Sloan Kettering Institute 
Radiology 
Consenting  Professional(s)/Department: 
Lisa Bodei, MD 
Diane Reidy-Lagunes, MD 
Neeta Pandit-Taskar, MD 
Jorge Carrasquillo, MD 
Ghassan Abou-Alfa, MD 
Andrea Cercek, MD 
Andrew Epstein, MD 
Radiology/MITS 
Medicine/GI  Oncology 
Radiology/MITS 
Radiology/MITS 
Medicine/GI 
Medicine/GI 
Medicine/GI 

Memorial Sloan Kettering Cancer Center 
IRB Number: 15-161 A(7) 
Approval date: 09-Sep-2020 
Page 2 of 39 
 
 
 
 
 
James Harding, MD 
Medicine/GI 
David Ilson, MD, PhD 
Medicine/GI 
Yelena Janjigian, MD 
Medicine/GI 
David Kelsen, MD 
Medicine/GI 
Nancy Kemeny, MD 
Medicine/GI 
Geoffrey Ku, MD 
Medicine/GI 
Eileen O’Reilly, MD 
Medicine/GI 
Leonard Saltz, MD 
Medicine/GI 
Neil Segal, MD, PhD 
Medicine/GI 
Armin Shahrokni, MD 
Medicine/GI 
Zsofia Stadler, MD 
Medicine/GI 
Anna Varghese, MD 
Medicine/GI 
Rona Yaeger, MD 
Medicine/GI 
Kenneth Yu, MD 
Medicine/GI 
 
 
Please Note: A Consenting Professional must have completed the mandatory Human 
Subjects Education and Certification Program. 
 
 
 
 
 
 
 
 
 
Memorial Sloan-Kettering Cancer Center 
1275 York Avenue 
New York, New York 10065 

Memorial Sloan Kettering Cancer Center 
IRB Number: 15-161 A(7) 
Approval date: 09-Sep-2020 
Page 3 of 39 
 
 
 
 
 
Table of Contents 
1.0 
PROTOCOL SUMMARY AND/OR SCHEMA .................................................................... 5 
2.0 
OBJECTIVES AND SCIENTIFIC AIMS ............................................................................. 6 
3.0 
BACKGROUND AND RATIONALE .................................................................................. 7 
3.1 
Somatostatin Receptor-based Imaging and Therapy of NETs ........................................ 7 
3.2 
Somatostatin Receptor Antagonist-based Imaging and Therapy of NETs ...................... 9 
4.0 
OVERVIEW OF STUDY DESIGN/INTERVENTION .............................................................. 13 
4.1 
Design.............................................................................................................................. 13 
4.2 
Intervention ........................................................................................................................... 14 
5.0 
THERAPEUTIC/DIAGNOSTIC AGENTS ........................................................................ 15 
6.0 
CRITERIA FOR SUBJECT ELIGIBILITY ............................................................................ 17 
6.1 
Subject Inclusion Criteria .................................................................................................. 17 
6.2 
Subject Exclusion Criteria ................................................................................................ 18 
7.0 
RECRUITMENT PLAN ................................................................................................................. 18 
8.0 
PRETREATMENT EVALUATION ................................................................................... 19 
9.0 
TREATMENT/INTERVENTION PLAN ............................................................................. 20 
9.1 
PET/CT Imaging ............................................................................................................... 20 
9.2 
Dosimetry Study ........................................................................................................... 21 
9.3 
177Lu-DOTA-JR11 Therapy ........................................................................................... 22 
9.4 
Follow-up ........................................................................................................................... 23 
9.5 
Stopping Rules ............................................................................................................. 24 
10.0 
EVALUATION DURING TREATMENT/INTERVENTION ................................................. 25 
11.0 
TOXICITIES/SIDE EFFECTS ................................................................................................. 26 
12.0 
CRITERIA FOR THERAPEUTIC RESPONSE/OUTCOME ASSESSMENT ..................... 31 
13.0 
CRITERIA FOR REMOVAL FROM STUDY .................................................................... 31 
14.0 
BIOSTATISTICS ............................................................................................................ 31 
15.0 
RESEARCH PARTICIPANT REGISTRATION AND RANDOMIZATION PROCEDURES 
33 
15.1 
Research Participant Registration .................................................................................... 33 
15.2 
Randomization ................................................................................................................. 33 
16.0 
DAT A M ANAGEMENT ISSUES ..................................................................................... 33 
16.1 
Quality Assurance............................................................................................................ 34 
16.2 
Data and Safety Monitoring ................................................................................................. 34 

Memorial Sloan Kettering Cancer Center 
IRB Number: 15-161 A(7) 
Approval date: 09-Sep-2020 
Page 4 of 39 
 
 
17.0 
PROTECTION OF HUMAN SUBJECTS ......................................................................... 35 
17.1 
Privacy ............................................................................................................................. 35 
17.2 
Serious Adverse Event (SAE) Reporting ............................................................................. 35 
17.2.1  .....................................................................................................................................  36 
18.0 
INFORMED CONSENT PROCEDURES................................................................................ 37 
19.0 
REFERENCES .................................................................................................................... 37 
20.0 
APPENDICES ................................................................................................................ 39 

Memorial Sloan Kettering Cancer Center 
IRB Number: 15-161 A(7) 
Approval date: 09-Sep-2020 
Page 5 of 39 
 
 
 
 
1.0 
PROTOCOL SUMMARY AND/OR SCHEMA 
 
Peptide-receptor radionuclide therapy (PRRT) with radiolabeled somatostatin (sst) analogs was 
developed in the 1990s (1), and is now frequently used in Europe for the treatment of metastatic 
neuroendocrine tumors (NETs) (2-4). However, not all patients respond well to PRRT. In 
addition, there are serious and potentially irreversible side effects, most notably chronic renal 
failure due to renal excretion of the radiopeptides (2, 5). Thus, there is a clear need to develop 
new ligands with higher tumor uptake and a more favorable tumor-to-kidney dose ratio. 
To address this need, members of our group have developed radiolabeled somatostatin 
receptor type 2 (sstr2) antagonists (6-10). Preclinical studies have indicated that these 
compounds bind to significantly more receptor sites than the sstr agonists currently used for 
PRRT (6). This finding was confirmed by quantitative  autoradiography of patient-derived tumor 
samples (11), which demonstrated a more than four-fold increase in the ex vivo binding of the 
somatostatin receptor antagonist 177Lu-DOTA-BASS when compared to the somatostatin 
receptor agonist 177Lu-DOTA-TATE. In a pilot imaging study with an 111In-labeled  DOTA-BASS, 
we have shown that this ligand detects significantly more metastases of NETs in patients than 
the current standard 111In-DTPA-Octreotide (9). We have also performed a preliminary clinical 
study comparing the dosimetry of a 177Lu-labeled  therapeutic sstr antagonist 177Lu-JR11 with 
177Lu-DOTA-TATE, an sstr agonist frequently used for PRRT. In this study, the antagonist 
demonstrated on average a three-fold higher tumor dose and a two-fold higher tumor-to-kidney 
ratio (10). 
The goal of this study is to evaluate the sstr antagonists, 68Ga-DOTA-JR11 and 177Lu-DOTA- 
JR11 as a pair of diagnostic/therapeutic radiopharmaceuticals (theranostics) in patients with 
NETs. Specifically, we will (i) assess biodistribution and tumor uptake of 68Ga-DOTA-JR11 and 
compare the sensitivity of 68Ga-DOTA-JR11 PET with 111In-DTPA-Octreotide SPECT (the 
current clinical standard); (ii) determine tumor and normal organ doses after administration of 
177Lu-DOTA-JR11; and (iii) obtain preliminary data on tumor response to 177Lu-DOTA-JR11. 
 
We will include 20 evaluable patients with, progressive, and inoperable well differentiated NETs. 
Patients will first undergo a PET/CT with 68Ga-DOTA-JR11. Patients with sufficient tumor uptake 
of 68Ga-DOTA-JR11 will be offered therapy with 177Lu-DOTA-JR11. Patients with no 68Ga- 
DOTA-JR11 positive disease will be replaced. We expect this to be the case in 10% or less of 
the patients. Therapy will be preceded by a dosimetric study to determine the amount of 
radioactivity that can be safely administered. The study will be performed under an MSKCC  
IND. 

Memorial Sloan Kettering Cancer Center 
IRB Number: 15-161 A(7) 
Approval date: 09-Sep-2020 
Page 6 of 39 
 
 
 
 
 
 
Figure 1. Flowchart giving an overview of the study procedures. 
 
 
 
2.1 
OBJECTIVES AND SCIENTIFIC AIMS 
 
Primary Objectives: 
 
1. To evaluate the safety, tolerability, and adverse event profiles of the theranostic pair of 
radiopharmaceuticals 68Ga-DOTA-JR11 and 177Lu-DOTA-JR11 in patients with 
advanced, well differentiated neuroendocrine tumors. 
2. To assess the biodistribution, tumor uptake, and dosimetry of the new diagnostic sstr2 
antagonists, 68Ga-DOTA-JR11 and 177Lu-DOTA-JR11. 
3. To obtain a preliminary comparison of the sensitivity of PET with 68Ga-DOTA-JR11 with 
the clinically used sstr agonist 111In-DTPA-octreotide. 
 
Secondary Objectives: 
 
1. To determine if 68Ga-DOTA-JR11 uptake correlates with the radiation dose to tumor and 
normal organs after administration of 177Lu-DOTA-JR11. 

Memorial Sloan Kettering Cancer Center 
IRB Number: 15-161 A(7) 
Approval date: 09-Sep-2020 
Page 7 of 39 
 
 
 
 
2. To obtain preliminary data on overall tumor response of 177Lu-DOTA-JR11 according to 
Response Evaluation Criteria in Solid Tumors guidelines, Version 1.1 (RECIST 1.1). 
3. To obtain preliminary data on progression-free survival, overall survival, and stable 
disease in patients treated with 177Lu-DOTA-JR11. 
 
 
3.1 
BACKGROUND AND RATIONALE 
 
To date, all clinical sstr imaging and therapy approaches have been based on sstr agonists. The 
sstr ligands described in this protocol are the first-in-class radiolabeled sstr antagonists. Despite 
the novelty of the tested compounds, the risk of failure for the clinical trial is low, since the 
effectiveness of radiolabeled sstr agonists is well known. The key difference between 
antagonists and agonists is the higher uptake and retention of antagonists in NETs , resulting in a 
higher radiation dose to the tumors and a lower radiation dose to the kidneys. This is likely to 
translate in a safer and more effective therapy of NETs if our study confirms the higher uptake 
and retention of sstr antagonists predicted from preclinical and pilot clinical studies (6, 9, 10). 
NETs are frequently perceived to represent a rare group of malignancies, but this is not entirely 
correct. There are about 15,000 new cases in the U.S. per year—about twice the number of 
Hodgkin’s lymphomas (12)—but the prevalence of the disease is much higher. More than 
100,000 patients are currently living with NETs in the U.S. (14), a higher number of patients 
than those with pancreatic and stomach cancer combined (12). Accordingly, there is a clear 
need to improve the diagnosis and therapy of NETs. This is especially true in the U.S., where 
PRRT is not available and sstr2-based imaging is still performed with a low-affinity sstr ligand 
(111-In-DTPA-octreotide,  OctreoScan®) (15). 
3.2 
Somatostatin Receptor-based Imaging and Therapy of NETs 
 
Tumor cells originating from neuroendocrine tissues generally express high levels of G 
protein-coupled receptors, which can be used as targets for therapeutic interventions 
(16). The most commonly overexpressed class of receptors are the somatostatin 
receptors (sstrs), specifically the somatostatin receptor subtype 2 (sstr2) (17). Using 
autoradiographic studies with radiolabeled somatostatin-28 and Tyr3-octreotide (an sstr 
ligand with predominant binding to sstr2), somatostatin receptors were found in more 
than 87% of patients with carcinoids of the gut or lung (54 of 62 patients) and in 100% of 
the pancreatic NETs (15 of 15). Homogenous expression of sstr2 was found throughout 
the tumor tissue and the level of expression was high, compared to surrounding normal 
tissues (17). 
Binding of somatostatin to sstr2 leads to internalization of the receptor (18) and inhibition 
of adenylate cyclase activity (19). This inhibits the secretion of various gastrointestinal 
hormones including gastrin, serotonin, and vasoactive intestinal polypeptide. The 
somatostatin analogs octreotide and lanreotide are therefore effective for controlling 
symptoms of hormone-producing NETs (16). In addition, they have anti-angiogenic 
effects and can inhibit the proliferation of NETs (16, 19). Treatment with octreotide or 

Memorial Sloan Kettering Cancer Center 
IRB Number: 15-161 A(7) 
Approval date: 09-Sep-2020 
Page 8 of 39 
 
 
 
 
lanreotide has been shown to improve progression-free survival in two randomized trials 
(20, 21). Monthly injections of a long-acting formulation of octreotide (octreotide LAR) 
improved progression-free survival of well differentiated NETs to 14.3 months compared 
to 6 months for placebo (20). Lanreotide improved progression-free survival from 18 
months to more than 24 months (21). 
The first clinically used radiolabeled somatostatin receptor ligands for imaging of NETs 
were 123I-Tyr3-octreotide and 111In-DTPA-octreotide (OctreoScan®), which is still in broad 
clinical use in the U.S. (15) Studies in the 1990s have indicated that planar and single 
photon computed emission tomography (SPECT) with 111In-DTPA-octreotide improves 
the detection of hormone active NETs and the staging of metastatic NETs compared to 
CT and MRI (22). Due to the progress of CT and MR technology, the sensitivity of both 
modalities for detection of NETs has significantly improved. In a retrospective review of 
104 patients in our institution, we found that 111In-DTPA-octreotide SPECT picked up 
only 6% more asymptomatic bone lesions (23). The key limitations of 111In-DTPA- 
octreotide are the need for delayed imaging 24 or even 48 hours post-injection because 
of slow blood clearance; the relatively high radiation dose caused by the comparatively 
long physical half-life of 111In; and the low spatial resolution of SPECT. 
Because of their high uptake in NETs, radiolabeled sstr ligands can be used not only for 
imaging, but also for treatment. To this end, H.R. Mäcke and his group have developed 
a variety of octreotide analogs that can be labeled with beta-emitting radiometals 
(Table 1). Various combinations of peptides, chelators, and radionuclides have been 
tested in the last decade, but by far the most commonly used radiopeptides are 90Y- 
DOTA-3Tyr-Octreotide (90Y-DOTA-TOC) and  177Lu-DOTA-3Tyr-Octretate (177Lu-DOTA- 
TATE). Table 2 summarizes the results of clinical studies evaluating 90Y-DOTA-TOC and 
177Lu-DOTA-TATE therapy in patients with NETs. 
Unfortunately, no randomized comparisons have been made between the two peptides  
or between PRRT and other forms of targeted therapy of NETs. Considering the 
heterogeneity of NETs and the difficulties in reproducibly assessing tumor response in 
patients with extensive metastatic disease, comparing the response rates reported by  
the individual  studies is problematic. Nevertheless, the objective response rates are 
markedly higher than reported in clinical trials with octreotide LAR (7), everolimus (21), 
and sunitinib (22). This indicates that PRRT is more likely to induce significant tumor 
shrinkage than these other forms of targeted therapy. Furthermore, objective responses 
to PRRT were not only observed in pancreatic NETs, but also in midgut and lung 
carcinoids (19, 20). For these tumors, there are currently no FDA-approved agents that 
can induce significant tumor shrinkage (23, 24). Furthermore, the duration of response to 
PRRT can be remarkably long. Kwekkeboom et al. report a median progression-free 
survival of 40 months from the start of treatment (19). 
 
 
Ligand (reference) 
sstr1 
sstr2 
sstr3 
sstr4 
sstr5 
SS-28 (24) 
5.2±0.3 
2.7±0.3 
7.7±0.9 
5.6±0.4 
4.0±0.3 

Memorial Sloan Kettering Cancer Center 
IRB Number: 15-161 A(7) 
Approval date: 09-Sep-2020 
Page 9 of 39 
 
 
 
 
 
Octreotide (24) 
>10,000 
2.0±0.7 
187±55 
>1,000 
22±6 
In-DTPA-octreotide (24) 
>10,000 
22±3.6 
182±13 
>1,000 
237±52 
Y-DOTA-TOC  (24) 
>10,000 
11±1.7 
389±135 
>10,000 
114±29 
Ga-DOTA-TOC  (24) 
>10,000 
2.5±0.5 
613±140 
>1,000 
73±21 
Y-DOTA-[Tyr3]-octreotate (24) 
>10,000 
1.6±0.4 
>1,000 
523±239 
187±50 
Ga-DOTA-[Tyr3]-octreotate 
(24) 
>10,000 
0.2±0.04 
>1,000 
300±140 
377±18 
Lu- DOTA[Ty3]-octreotate (11) 
>1,000 
1.5±0.4 
>1000 
453±179 
547±160 
In-DOTA-BASS  (6) 
n.d. 
9.4±0.4 
n.d. 
n.d. 
n.d. 
DOTA-JR11 (7) 
>1,000 
0.72±0.12 
>1,000 
>1,000 
>1,000 
Lu-DOTA-JR11  (7) 
>1000 
0.73±0.15 
>1000 
>1000 
>1000 
Ga-DOTA-JR11  (7) 
>1000 
29±2.7 
>1000 
>1000 
>1000 
 
 
Table 1. Overview  of the affinity profiles  of radiolabeled  somatostatin receptor binding peptides. 
Data show the concentration in nM for 50% inhibition of binding (IC50) of the radiolabeled  natural 
ligand somatostatin-28.  n.d. - Not determined.  Data show mean and standard deviation. 
Treatment with 177Lu-DOTA-TATE and 90Y-DOTA-TOC is generally very well tolerated. 
However, renal toxicity is an important side effect since the peptides are excreted by the 
kidney and partly stored in the renal tubulus system (25). Renal toxicity grade 4-5 has 
been reported in 0.4% to 9.2% of the treated patients (19, 20). The cumulative radiation 
dose to the kidneys is currently limited to 23 Gy in order to decrease the risk of renal 
toxicity (26). Kidney dose typically limits the amount of 177Lu-DOTA-TOC and 90Y-DOTA- 
TATE that can safely be administered to a patient. 
 
First  author (reference) 
Peptide 
N 
CR 
PR 
SD 
PD 
Response 
criteria 
Otte et al. 1999 (1) 
90Y-TOC 
16 
0 
1 (6%) 
14 (88%) 
1 (6%) 
Own 
definition 
Bodei et al. 2003 (25) 
90Y-TOC 
21 
0 
6 (29%) 
11 (52%) 
4 (19%) 
WHO 
Valkema et al. 2006 (26) 
90Y-TOC 
58 
0 
5 (9%) 
29 (53%) 
14 (25%) 
SWOG 
Bushnell et al. 2010 (27) 
90Y-TOC 
90 
0 
4 (4%) 
63 (70%) 
23 (26%) 
SWOG 
Kwekkeboom et al. 2008 (3) 
177Lu- 
TATE 
310 
5 (2%) 
86 (28%) 
107 
(35%) 
61 (20%) 
SWOG 
Imhof et al. 2011 (2) 
90Y-TOC 
1109 
7 
(0.6%) 
371 
(34%) 
436 
(39%) 
295 
(27%) 
Own 
definition* 
Table 2. Overview  of clinical trials evaluating  90Y-DOTA-TOC  and 177Lu-DOTA-TATE   therapy in 
patients with NETs. N – numbers  of patients included. *Any measurable decrease or increase of 
the sum of longest tumor diameters was considered PR or PD, respectively. 
3.3 
Somatostatin Receptor Antagonist-based Imaging and Therapy of 
NETs 
In order to improve imaging and treatment of NETs, the study PI have developed a new 
class of radiolabeled somatostatin receptor ligands. In contrast to all previously studied 
radiolabeled somatostatin receptor ligands, these compounds are somatostatin 
antagonists, not agonists. Previous work has ignored somatostatin antagonists, because 

Memorial Sloan Kettering Cancer Center 
IRB Number: 15-161 A(7) 
Approval date: 09-Sep-2020 
Page 10 of 39 
 
 
 
 
it was believed that internalization of the ligand is key for high tumor uptake and 
retention. Since sstr antagonists lack receptor-mediated internalization, they were 
considered not to be suitable for radionuclide therapy. 
However, preclinical studies have shown that sstr-expressing tumors demonstrate higher 
uptake of radiolabeled sstr antagonists than sstr agonists (6). In mice bearing HEK-sstr2 
tumors, tumor uptake of the antagonist 111In-DOTA-BASS was twice as high as the 
uptake of the potent agonist 111In-DTPA-TATE, despite the fact that the affinity of DOTA- 
BASS for sstr2 is lower than that of DTPA-TATE (Table 1). Importantly, antagonists not 
only demonstrated higher peak uptake, but were also retained longer within the tumors. 
This unexpected finding is probably explained by a markedly higher number of binding 
sites for sstr antagonists as compared to agonists. Scatchard analysis showed more  
than ten times the number of binding sites for 111In-DOTA-BASS (Bmax = 354±14 pM) 
than for 111In-DTPA-TATE (Bmax = 23±1.0 pM). Ex vivo studies with human tumors (12) 
have also demonstrated markedly higher binding of sstr2 antagonists than of sstr2 
agonists (11). This suggests that antagonists bind to more receptor confirmations 
(activated and inactive) than agonists. 
Based on these encouraging data, the study PI performed a pilot trial at the University of 
Freiburg that compared the biodistribution and tumor uptake of the sst2 receptor 
antagonist 111In-DOTA-BASS with the clinically used 111In-`DTPA-octreotide 
(OctreoScan®) (9). These two ligands have a similar affinity for sstr2 (Table 1). In this 
study, 111In-DOTA-BASS detected 25/28 lesions (89.3%), whereas 111In-DTPA- 
Octreotide detected only 17/28 (60.7%) lesions (P = 0.013). In pair-wise comparisons, 
111In-DOTA-BASS showed significantly higher tumor and lower renal uptake than 111In- 
DTPA-Octreotide at 4 hours post-injection, resulting in up to 5.2 times higher tumor-to- 
kidney uptake ratios (9). This study demonstrated for the first time the feasibility of using 
sstr2 antagonists for imaging of NETs and suggested that sstr antagonists may enable 
the delivery of higher radiation doses to NETs than sstr2 agonists. 
The affinity of 111In-DOTA-BASS for sstr2 is lower than for the therapeutically used 
peptides 90Y-DOTA-TOC or 177Lu-DOTA-TATE (Table 1). In our subsequent studies, we 
therefore used a new somatostatin antagonist, DOTA-JR11 (Table 1), which 
demonstrates a subnanomolar affinity for sstr2 (Table 1). Labeling with Lutetium did not 
affect the affinity for sstr2. In contrast, labeling with Gallium unexpectedly decreased the 
affinity (Table 1). Nevertheless, PET and biodistribution studies in mice bearing sstr2- 
expressing xenografts demonstrated slightly higher tumor uptake of 68Ga-DOTA-JR11 
than the high-affinity sstr2 agonist 68Ga-DOTA-TATE (7). This indicates that the lower 
affinity of 68Ga-DOTA-JR11 for sstr2 is compensated by its ability to bind to more 
receptor sites than 68Ga-DOTA-TATE. Since 68Ga-DOTA-TATE is clinically clearly 
superior to 111In-DTPA-Octreotide (28-30), these findings are promising for the clinical 
use of 68Ga-DOTA-JR11 for NET imaging. 

Memorial Sloan Kettering Cancer Center 
IRB Number: 15-161 A(7) 
Approval date: 09-Sep-2020 
Page 11 of 39 
 
 
 
 
 
 
 
 
Table 3. Characteristics of patients treated with 177Lu-DOTA-JR11. 
 
 
 
177Lu-DOTA-JR11 was studied in four patients with progressive, unresectable NETs at 
the University of Freiburg in Germany. Renal function was impaired in all patients, thus 
limiting the amount of 177Lu-DOTA-TATE that could be safely administered. These 
patients were offered to undergo a dosimetry study with 177Lu-DOTA-TATE and 177Lu- 
DOTA-JR11. If this study indicated a higher tumor radiation dose of 177Lu-DOTA-JR11 
and an acceptable renal radiation dose, patients were offered treatment with 177Lu- 
DOTA-JR11 (10). Table 3 summarizes the clinical characteristics of the patients. 
After infusion of an arginine/lysine solution (kidney protection), patients were injected 
with 1-2 GBq 177Lu-DOTA-TATE and 177Lu-DOTA-JR11 (crossover design in an interval 
of three weeks). No acute adverse effects of 200 μg 177Lu-DOTA-JR11 were observed. 

Memorial Sloan Kettering Cancer Center 
IRB Number: 15-161 A(7) 
Approval date: 09-Sep-2020 
Page 12 of 39 
 
 
 
 
Dosimetric calculation was possible for 13 lesions. Table 4. Radiation doses for 177Lu- 
 
DOTA-TATE  and 177Lu-DOTA-JR11  and treatment effects for 13 lesions evaluated  in the 4 
patients. 
 
 
 
In pair-wise comparisons, 177Lu-DOTA-JR11 showed significantly higher tumor doses 
than 177Lu-DOTA-TATE (10.1 ± 8.2 vs. 3.2 ± 3.4 Gy/GBq, P < 0.001). Importantly, the 
mean tumor-to-kidney dose ratio was more than two-fold higher for 177Lu-DOTA-JR11 
than for 177Lu-DOTA-TATE (6.0 ± 5.6 vs. 2.5 ± 2.3, P < 0.01). As a result, all four 
patients were treated with 177Lu-DOTA-JR11 (up to 15.2 GBq in two-three cycles every 
three months): two patients showed a partial response, one patient had stable disease, 
and one patient progressed (Table 3). These results are remarkable given the low dose 
of 177Lu administered and the advanced stage of these tumors. Follow-up laboratory 
evaluations showed only a mild increase of serum creatinine and mild, temporary 
myelosuppression. 

Memorial Sloan Kettering Cancer Center 
IRB Number: 15-161 A(7) 
Approval date: 09-Sep-2020 
Page 13 of 39 
 
 
 
 
 
 
 
One patient with a high-grade NET of 
the bladder died due to progressive 
disease, whereas the other patients are 
well, with no evidence of progressive 
disease (Table 3). 
One patient experienced a short 
episode of ﬂush just after injection of 
177Lu-DOTA-JR11. Another patient 
developed grade 3 thrombocytopenia 
(41,000/mm3), which completely 
recovered within eight weeks after 
injection of 177Lu-DOTA-JR11 (Table 3). 
There was no relevant decrease of 
tubular kidney function within 12 months 
of follow-up (mercaptoacetyltriglycine 
clearance, 136 mL/min/1.73 m2  vs. 127 
mL/min/1.73 m2). Also, creatinine levels 
did not change significantly before and 
after treatment (approximately 12 
months post-treatment; 1.32 mg/dL vs. 
1.39 mg/dL) (10). 
 
The radiation dosimetry of 177Lu-DOTA- 
JR11 in comparison to 177Lu-DOTA- 
TATE for the four patients studied is 
summarized in Table 5. 
Table 5. Radiation  dosimetry calculations. Data 
show mean and standard deviation. 
 
 
 
4.1 
OVERVIEW OF STUDY DESIGN/INTERVENTION 
 
4.2 
Design 
 
Patient will first undergo PET/CT imaging with 68Ga-DOTA-JR11 to determine eligibility 
for treatment with 177Lu-DOTA-JR11 (Figure 1). Only patients that have 68Ga-DOTA- 
JR11 uptake greater than that in the liver in at least one metastasis of more than 2 cm 
diameter will be considered for therapy. Patients with 68Ga-DOTA-JR11 positive disease 
will then undergo a dosimetry study to determine the amount activity of 177Lu-DOTA- 
JR11 that can be safely administered. Based on the human biodistribution we expect the 
kidney and the bone marrow to be the two dose limiting organs. The dose limit for the 
kidney will be 23 Gy as suggested by the QUANTEC guidelines for external beam 
radiotherapy   (https://www.astro.org/Clinical-Practice/Quantec/QUANTEC.aspx). We 

Memorial Sloan Kettering Cancer Center 
IRB Number: 15-161 A(7) 
Approval date: 09-Sep-2020 
Page 14 of 39 
 
 
 
 
realize that this dose limit has been defined for external beam therapy and that higher 
doses may be feasible for low dose rate internal radiation. However, since the dose 
distribution in the kidney is heterogeneous we will use this relatively low whole organ  
limit as a safety precaution. In addition, the red marrow dose will be limited to 1.5 Gy. 
Again this a relatively low value, especially as the radioactivity is administered over 
multiple cycles. Other organs are not expected to become dose limiting, but we will 
compare the radiation doses for all organs with detectable 177Lu-DOTA-JR11 uptake with 
the QUANTEC dose limits and adjust the therapeutic activity if necessary. 
The clinical intention is that the combined dosimetry and therapy administrations of 
177Lu-DOTA-JR11 will deliver the lower of the two dose limits (23 Gy to kidney, 1.5 Gy to 
red marrow). The administered activity for the pre-therapy dosimetry study will be fixed 
(1.85 GBq = 50 mCi). Thereafter, the balance of activity that is predicted to deliver the 
lower of the two dose limits will be calculated. This will be split into two equal amounts to 
be delivered approximately 3 months apart. However if the first treatment results in 
estimated doses that differ from the initial predictions, the second treatment will be 
adjusted (either decreased or increased) so that the intended dose limits are achieved. 
Note that administered activities listed will be +/- 10% as per institutional practice. 
4.3 
Intervention 
 
68Ga-DOTA-JR11 PET/CT Imaging 
 
Following informed consent, eligible patients will first undergo a PET/CT study with 
approximately 150-200 MBq of 68Ga-DOTA-JR11 as described in section 9.1. 
Normal and altered biodistribution of 68Ga-DOTA-JR11 
 
68Ga-DOTA-JR11 is expected to demonstrate a similar biodistribution as other 
somatostatin receptor ligands, such as 111In-Octreotide, 68Ga-DOTA-TATE, and 177Lu- 
DOTA-JR (10). Pituitary gland, adrenal glands and the pancreatic head are expected to 
demonstrate focal uptake of 68Ga-DOTA-JR11. In addition, we expect diffuse tracer 
uptake by the liver, spleen and kidneys as well as excretion of activity to the bladder with 
no or low hepatobiliary excretion. 
Altered biodistribution is defined as any deviation from the expected biodistribution, 
specifically focal uptake in lesions or absence of focal uptake in organs with known 
physiologic expression of somatostatin receptors (pituitary gland, adrenal glands and 
pancreatic head). Another sign of an altered biodistribution is predominantly 
hepatobiliary excretion of the tracer. 
 
Image Interpretation 
 
PET/CT scans will first be interpreted without information on the results of other imaging 
modalities. Any lesions with focal radiotracer uptake not explained by physiologic sstr2 
expression will be interpreted as metastatic disease. 

Memorial Sloan Kettering Cancer Center 
IRB Number: 15-161 A(7) 
Approval date: 09-Sep-2020 
Page 15 of 39 
 
 
 
 
The likelihood of malignancy will be described by a 5-point Likert scale. Following the 
blinded read of the 68Ga-DOTA-JR11 PET/CT scan, all recorded findings will be 
correlated with the results of 111In-Octreotide SPECT, and CT/MRI performed as part of 
standard clinical care. The relative sensitivity of 68Ga-DOTA-JR11 will be determined by 
a consensus of the clinical investigators and systemic analysis of all available imaging 
studies and follow-up. We will consider a score of 3 or above malignant and a score of 1 
or 2 as benign for the purposes of this protocol. 
177Lu-DOTA-JR11 Dosimetry 
 
If 68Ga-DOTA-JR11 uptake by metastases with a diameter of more than 2 cm is less 
than the physiologic radiotracer uptake by the liver, no further imaging and therapy will 
be performed as part of the study, as it is unlikely that patients with this low radiotracer 
uptake will benefit from PRRT (2). 
All other patients will undergo a dosimetric study with 1850 MBq (less than 100 μg 
peptide) of 177Lu-DOTA-JR11. This amount of radioactivity is required in order to obtain 
images with sufficient count statistics to reliably quantify radiotracer uptake in tumor 
lesions and organs (the abundance of imagable gamma emissions for 177Lu is only 
11%). Replacing 177Lu with another radiometal such as 111In carries the risk of a different 
tumor uptake, because the radiometal can have a significant impact on the affinity of 
sstr2 antagonists (Table 1). 
177Lu-DOTA-JR11 Therapy 
 
From the results of the dosimetry study, we will determine the balance of activity of 
177Lu-DOTA-JR11 that can be administered without exceeding the radiation dose limits. 
This activity will be split into two equal amounts to be delivered in two cycles, 
approximately three months apart. However if the first treatment cycle results in 
estimated doses that differ from the predictions, the activity administered for second 
treatment cycle will be adjusted so that the dose limits are maintained. Based on the 
preliminary clinical data (table 5), we anticipate that the typical activities of 177Lu-DOTA- 
JR11 administered over the full course of dosimetry and treatment will be approximately 
1.85, 5.4, and 5.4 GBq (50, 147, and 147 mCi, respectively). After each therapy cycle, 
patients will be followed clinically for three months. 
 
 
5.0 
THERAPEUTIC/DIAGNOSTIC AGENTS 
 
[68Ga]-DOTA-JR11 and [177Lu]-DOTA-JR11 
 
This study will use the investigational theranostic products [68Ga]-DOTA-JR11 and [177Lu]- 
DOTA-JR11 which are manufactured and released by the Radiochemistry and Molecular 
Imaging Probes (RMIP) Core at MSKCC following the guidelines of GMP appropriate for Phase 
I clinical trials, local and Institutional Quality Controls and in full compliance with the applicable 
FDA and local regulatory bodies. 68Ga- and 177Lu- radioligands are obtained from qualified 

Memorial Sloan Kettering Cancer Center 
IRB Number: 15-161 A(7) 
Approval date: 09-Sep-2020 
Page 16 of 39 
 
 
 
 
vendors, accompanied by a certificate of analysis. The investigational products are delivered to 
Nuclear Pharmacy and compounded/dispensed by a pharmacist per physician order. The 
Nuclear Pharmacy operates in full compliance with the applicable FDA and local regulatory 
bodies. 
To ensure administration within the expiration time, [68Ga]-DOTA-JR11 and [177Lu]-DOTA-JR11 
are delivered to Nuclear Pharmacy labeled with a 6 and 3 hour expiration and placed in 
inventory, which will not allow dispensing of an expired product. A licensed pharmacist 
dispenses each labeled product in accordance with the physician order. 
The chemical structure of 68Ga/177Lu-DOTA-JR11 is shown in Figure 2. DOTA-JR11 is a high- 
 
 
affinity antagonist of somatostatin at the somatostatin type 2 receptor (sstr2). This is the subtype 
of somatostatin receptors most commonly overexpressed in GEP-NET tumors. DOTA-JR11 has 
low affinity for other somatostatin receptors (Table 1). 
This study will be performed under an FDA approved IND for 68Ga- DOTA-JR11 and 177Lu- 
DOTA-JR11. The synthesis, reagents, testing and composition of the final product 68Ga/177Lu- 
DOTA-JR11 are described in detail in the chemistry, manufacturing and controls (CMC) section 
of the IND application. The synthesis method is based on the published previous human 
experience at the University of Freiburg (10). 68Ga-DOTA-JR11 is administered as an 
intravenous microdose (<100 µg peptide mass) and will contain approximately 150-200 MBq 
radioactivity. In the dosimetric study, 177Lu-DOTA-JR11 is given at a dose of 1,850-6,000 MBq 
(<100 µg peptide mass). The therapeutic radioactive dose of 177Lu-DOTA-JR11 will be 
determined by the dosimetric study. Based on the preliminary clinical data described above, we 
anticipate that the typical amounts of 177Lu-DOTA-JR11 administered over the full course of 
dosimetry and treatment will be approximately 1.85, 5.4, and 5.4 GBq (50, 147, and 147 mCi, 
respectively). A lower mass dose than 100 µg of 68Ga-DOTA-JR11 is technically feasible for the 
imaging studies, but may lead to systematic differences in the biodistribution of 68Ga-DOTA- 
JR11 and 177Lu-DOTA-JR11. Therefore, we will use a similar peptide mass for both 68Ga-DOTA- 
JR11 and 177Lu-DOTA-JR11. 
 
 
Figure 2. Chemical  structure of 68Ga/177Lu-DOTA-JR11. 
68Ga 
177Lu 

Memorial Sloan Kettering Cancer Center 
IRB Number: 15-161 A(7) 
Approval date: 09-Sep-2020 
Page 17 of 39 
 
 
 
 
 
 
 
Renal Protection Solutions: Aminosyn  II (10%), Clinisol (15%), or “2.5% L-Lysine HCl – 
2.5% L-Arginine HCl, Renal Protectant Solution, RMIPC” 
 
Aminosyn II (10%) is an FDA approved amino acid injection obtained from MSKCC pharmacy. 
 
Baxter 15% CLINISOL (sulfite-free) is an FDA approved amino acid injection obtained from 
MSKCC compounding pharmacy. 
“2.5% L-Lysine HCl – 2.5% L-Arginine HCl, Renal Protectant Solution, RMIPC” will be 
compounded under the practice of pharmacy compounding pursuant to a prescription from a 
physician for a specific patient by RMIP Core at MSKCC. 
 
 
6.1 
CRITERIA FOR SUBJECT ELIGIBILITY 
 
Only adult patients will be studied (≥ 18 years old). There will be no other restrictions in terms of 
age or race. Patients must be referred by members of MSK’s Medical Oncology Service. 
Due to special dosimetry considerations in pediatric patients, children will be excluded from this 
study. There is no safety data in children at this point. 
6.2 
Subject Inclusion Criteria 
 
• 
Ability to understand and the willingness to sign a written informed consent 
document 
• 
Adults ≥ 18 years old 
• 
Histologically or cytologically confirmed metastatic and/or unresectable 
progressive, well differentiated carcinoid or pancreatic NET carcinoids 
• 
Progressive metastatic disease defined by one of the following, occurring within 6 
months of study entry: 
o At least a 20% increase in radiologically or clinically measurable disease 
o Appearance of any new lesion 
o Symptomatic disease (including worsening hormonal symptoms or 
symptoms related to tumor burden) 
• 
Measurable disease as defined by RECIST 1.1. 
• 
At least one metastasis must show uptake of 111In-DTPA-octreotide  on SPECT 
that is higher than the physiologic radiotracer uptake by the liver 
• 
ECOG performance status ≤ 2 (Karnofsky ≥ 60%) 
• 
Patients must have normal organ and marrow function as defined below: 
o Leukocytes ≥ 3.0 x 109/L 
o Absolute neutrophil count (ANC) ≥ 1.5 x 109/L 
o Hemoglobin ≥ 9.0 g/dL 
o Platelets ≥ 200 x 109/L 
o Total bilirubin ≤ 1.25 x Upper Limit Normal (ULN) 

Memorial Sloan Kettering Cancer Center 
IRB Number: 15-161 A(7) 
Approval date: 09-Sep-2020 
Page 18 of 39 
 
 
 
 
o AST (SGOT)/ ALT(SGPT) ≤ 2.5 x ULN with liver metastases 
o Alkaline phosphatase < 2 x ULN (if known liver or bone disease) 
o Serum albumin > 30 g/L, or serum albumin = 30 g/L but normal 
prothrombin time 
o Creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) calculated CrCl ≥ 60 
mL/min/1.73m2 
• 
Women of childbearing potential and men must agree to use adequate 
contraception prior to study entry and for the duration of study participation 
• 
Previous local therapy (e.g., chemoembolization or bland embolization) is  
allowed if completed > 6 weeks prior to study entry. For such patients, there must 
be either progression of measurable disease documented within the treatment 
field, or measurable progressive disease outside the treatment field prior to study 
entry. 
• 
Previous chemotherapy and/or investigational agents are allowed if completed > 
4 weeks prior to study entry (> 6 weeks if last regimen contained bis-chloroethyl 
nitrosourea (BCNU) or mitomycin C). For patients who received systemic therapy 
prior to study entry, there must be documented progression of measurable 
disease since receiving systemic therapy prior to study entry. 
• 
Patients must not have disease that is currently amenable to surgery. Prior 
surgery is allowed no less than 6 weeks prior to study entry. 
6.3 
Subject Exclusion Criteria 
 
• 
History of allergic reactions attributed to compounds of similar chemical or 
biologic composition to 177Lu-DOTA-JR11 as assessed from medical records 
• 
Life expectancy < 6 months as assessed by the treating physician. 
• 
Treatment with short-acting somatostatin analogs less than 3 days and 
Sandostatin®  depot injection less than 5 weeks before scanning and treatment 
• 
Uncontrolled, intercurrent illness including, but not limited to, ongoing or active 
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac 
arrhythmia, or psychiatric illness/social situations that would limit compliance with 
study requirements 
• 
Women who are pregnant or breastfeeding 
• 
Toxicities from prior therapies that have not resolved to grade 1 or grade 0 
• 
Known CNS metastases and/or carcinomatous meningitis 
• 
Active malignancy of metastatic potential other than the known carcinoid or 
pancreatic NET within the past three years 
• 
>20% bone marrow external beam radiotherapy and/or previous radioisotope 
therapy 
 
 
7.0 
RECRUITMENT PLAN 

Memorial Sloan Kettering Cancer Center 
IRB Number: 15-161 A(7) 
Approval date: 09-Sep-2020 
Page 19 of 39 
 
 
 
 
A member of the patient’s treatment team at MSK will identify potential study participants. Adults 
of all races and ethnic groups will be considered for study participation. Candidates must 
conform to all inclusion and exclusion criteria to be accepted into the study. 
If the investigator is a member of the treatment team, s/he will screen their patients’ medical 
records for suitable research participants and discuss the study and the possibility of enrolling in 
the research study. Potential subjects contacted by their treating physician will be referred to the 
investigator/research staff of the study. 
 
 
8.1 
PRETREATMENT EVALUATION 
 
Before any protocol-specified procedures are conducted, each prospective participant must sign 
an informed consent form. The following screening tests and procedures must be obtained  
within four weeks prior to study entry: 
• 
Medical history confirmation of tumor diagnosis by submission of archived tumor tissue 
(archived material can be submitted any time prior to study entry). 
• 
Physical examination, including vitals 
• 
Documentation of concurrent medications 
• 
Karnofsky or ECOG performance status 
• 
EKG 
• 
Laboratory assessment (within two weeks prior to study entry): 
o Complete Blood Count (CBC) 
o Comprehensive Metabolic  Panel (CMP) 
o PTT, PT/INR 
o Chromogranin A 
o Urinalysis 
o 
99mDTPA scan with filtration rate 
o Hormone levels (if patient is symptomatic and the tumor is functional; hormone 
levels will be based on tumor type); for example: 
▪ 
Carcinoid tumor: 24-hr HIAA 
▪ 
VIPoma: VIP 
▪ 
Glucagonoma: glucagon 
▪ 
Insulinoma: insulin 
▪ 
Gastrinoma: gastrin 
▪ 
Somatostatinoma: somatostatin 
• 
111In-Octreotide SPECT (within 8 weeks of study entry) 
• 
CT triphasic or MRI of the liver 
 
To be completed within 7-14 days prior to treatment: 
▪ Physical exam, including vital signs 
▪ Review of prior/concomitant medications 
▪ Performance status 

Memorial Sloan Kettering Cancer Center 
IRB Number: 15-161 A(7) 
Approval date: 09-Sep-2020 
Page 20 of 39 
 
 
 
 
▪ CBC, CMP 
▪ LDH 
▪ Haptoglobin 
▪ Serum or urinary pregnancy test in women of child-bearing age. This will be 
performed prior to each administration of radioactivity (diagnostic or therapeutic). 
▪ Tc-99m DTPA scan with GFR determination. This will be repeated within 2 weeks 
prior to second therapy and 10 to 14 weeks after second therapy. 
 
 
9.0 
TREATMENT/INTERVENTION PLAN 
Drug Accountability 
The investigator is obliged to keep sufficient documentation of the delivery and use of the 
investigational product. These records will include administration date/time, calibration  
date/time, quantity, patient code, lot number, and date of destruction. The investigator should 
maintain records that adequately document that the patients were provided the dose specified in 
the protocol and reconcile the medication received for the study. The label of each vial will 
contain the patient code and lot number, and patient and radiopharmaceutical information will  
be entered in the radiopharmacy drug accountability forms. The investigator may assign some  
or all of his/her duties regarding drug accountability to an appropriate individual such as a 
pharmacist or nuclear medicine technician, under the supervision of the investigator. 
9.1 
PET/CT Imaging 
 
No specific patient preparation is required before 68Ga-DOTA-JR11 injection. One 
intravenous catheter (Hep-Lock) will be placed by staff in the Molecular Imaging and 
Therapy Service for radiopharmaceutical administration. Vital signs will be obtained prior 
to 68Ga-DOTA-JR11 injection. 
Images will be corrected for attenuation and scatter and adjusted for system sensitivity, 
and will provide parametric data in terms of standardized uptake values (SUV) (= MBq 
found/gm tissue/ MBq injected/gm body mass). 
In order to provide reproducible clinical data, we will acquire all 68Ga-DOTA-JR11 
PET/CT scans on GE PET/CT 690 and 710 scanners (or a newer-generation scanner), 
providing reconstructed images with the same spatial resolution. Intravenous injection of 
68Ga-DOTA-JR11 will be given as a bolus. In all patients a PET-CT scan extending from 
top of skull to mid-thigh will be performed to determine the biodistribution 60-70 min after 
injection. We will perform a low-dose CT scan for attenuation correction and anatomical 
localization. Total acquisition time for these studies will be less than 40 min. 
In 6 patients (3 female and 3 male patients) additional imaging studies will be performed 
to obtain data on the dosimetry of 68Ga-DOTA-JR11. These studies will include a 
dynamic PET study of the upper abdomen including (parts of) the left ventricle, liver and 
kidneys to study the initial distribution of 68Ga-DOTA-JR11 for 25 minutes after injection. 

Memorial Sloan Kettering Cancer Center 
IRB Number: 15-161 A(7) 
Approval date: 09-Sep-2020 
Page 21 of 39 
 
 
 
 
This will be followed immediately by a PET/CT scan extending from the top of the skull 
to mid-thighs. The total duration for patients undergoing these enhanced studies for 
radiation dosimetry is approximately 85 minutes. Radiation doses will be calculated 
using OLINDA/EXM using the same principles described in section 9.2 for 177Lu-DOTA- 
JR11. 
9.2 
Dosimetry Study 
 
The dosimetry study will begin within 5 weeks of completion of PET imaging. An infusion 
of 2,000 mL renal protectant solution will be initiated approximately 30 minutes before 
and continued for 3.5 hours after the 177Lu-DOTA-JR11 injection to inhibit tubular 
reabsorption of the radiopeptide (25). This solution contains 21 g lysine and 20 g 
arginine and will be infused at constant rate of 500 ml/hr. The same amino acid infusion 
schedule will be used during treatment with 177Lu-DOTA-JR11. Patients may receive 8 
mg of the 5-HT3  antagonist Ondansetron I.V. and/or other antiemetics, as clinically 
indicated, prior to the start of the amino acid infusion in order to prevent nausea and 
vomiting, potentially caused by the amino acid infusion. In case of persistent 
nausea/vomiting despite these measures infusion rate can be lowered and the duration 
of the amino acid infusion extended. In such situations, the scan at 1-5 hours post 
injection will be adjusted and completed following the amino acid infusion. It will not be 
considered a protocol violation. 
For the dosimetry study, patients will undergo whole body planar imaging at nominal 
times of approximately 1-5, 18-30, 66-120, and 144-192 hours post-injection with a 
SPECT/CT study of the abdomen, including kidneys and sites of known disease, to be 
performed at 18-30 hours. 
Radiation-absorbed doses to kidneys, red marrow, whole body and any individual 
organs displaying 177Lu-DOTA-JR11 accumulation will be calculated based on patient 
images and blood-based measurements. Specifically, activity-time curves for normal 
tissues will be generated from region-of-interest (ROI) analysis of conjugate view whole 
body scans supplemented by the single SPECT-CT scan. Activity-time curves for heart 
contents and red marrow will be generated from the measured blood values. Activity- 
time curves will be integrated (either analytically or numerically as appropriate) to yield 
residence times used as input to the FDA-approved dosimetry software package 
OLINDA/EXM,  which will then generate absorbed dose estimates to normal tissues. 
Additional  dosimetry analysis will include: (1) lesion dose estimates based on ROI data 
assuming only self-dose; and (2) if differential retention in cortical and medullary sub- 
regions of the kidney is observed, the SPECT images will be used to quantify partitioning 
and enable sub-regional absorbed dose estimates. 
Blood Samples 
 
Blood samples will be drawn at approximately 5-10 min, 15-20 min, 30-40 min, 60-90 
min, 120-150 min, and 4-6 hours post-injection and, subsequently, at the times of 
imaging. These data will be used to determine the clearance of the radiotracer from the 

Memorial Sloan Kettering Cancer Center 
IRB Number: 15-161 A(7) 
Approval date: 09-Sep-2020 
Page 22 of 39 
 
 
 
 
blood and calculate the radiation dose to red marrow. Specifically, absorbed dose to red 
marrow is calculated as the sum of self-dose from activity in the marrow itself (estimated 
from the activity concentration in blood) and cross-dose from activity in other organs and 
from the generalized remainder of body. The calculation is performed using the 
OLINDA/EXM  dosimetry software package. For red marrow we make the assumption, 
common in radiation dose calculations for radiolabeled small molecules, that the activity 
concentration in the marrow is the same as that measured in blood. A standard value 
(taken from OLINDA/EXM)  is used for the total red marrow mass or, if the patient is 
significantly heavier than “standard human”, a rescaled value is used, based on the ratio 
of patient mass to standard mass. The total activity in the red marrow is integrated with 
respect to time to derive the AUC which is then divided by the administered activity to 
yield the residence time for red marrow. This, together with all the other residence times 
is input into OLINDA/EXM to generate absorbed radiation doses. 
9.3 
177Lu-DOTA-JR11 Therapy 
 
9.3.1 
Treatment Cycle 1 
 
Cycle 1 will begin within 6 weeks of the completion of dosimetry study. Patients will be 
given an intravenous injection of 177Lu-DOTA-JR11 over 5-10 minutes. An infusion of 
2,000 mL renal protectant solution will be initiated approximately 30 minutes before and 
continued for 3.5 hours after the 177Lu-DOTA-JR11 injection to inhibit tubular 
reabsorption of the radiopeptide (25). This solution contains 21 g lysine and 20 g 
arginine and will be infused at constant rate of 500 ml/hr. Imaging and blood sample 
collections will be performed at the same times as described for the dosimetry study and 
radiation doses calculated. 
The activity of 177Lu-DOTA-JR11 administered per cycle will not exceed 200 mCi (7.4 
GBq) independent from the radiation dose to the kidneys and/or red marrow. 
9.3.2 
Treatment Cycle 2 
 
Cycle 2 will be performed 10-14 weeks after cycle 1 if the following criteria are fulfilled: 
 
• 
No Grade 2 or higher platelet toxicity 
• 
No other grade 3 or 4 hematologic toxicity 
• 
< 40% increase of serum creatinine/decrease of creatinine clearance 
• 
Other grade 3 or 4 toxicity possibly related to 177Lu-DOTA-JR11 therapy 
 
The second treatment cycle can be postponed for up to 12 weeks for grade 3 toxicities 
to resolve to a level that meets the criteria shown above. If the toxicities have not 
resolved by this time, the patient is considered as having excessive toxicity and will not 
receive a second cycle of 177Lu-DOTA-JR11 therapy. 
Treatment will be administered as for cycle 1 with the possibility of a revised activity of 
177Lu-DOTA-JR11, depending on the doses calculated for the previous cycle. Infusion of 
renal protectant solution will be administered as described for treatment cycle 1. The 

Memorial Sloan Kettering Cancer Center 
IRB Number: 15-161 A(7) 
Approval date: 09-Sep-2020 
Page 23 of 39 
 
 
 
 
same set of imaging, blood sampling, and radiation dose calculations will be performed. 
Patients will be monitored for adverse events. Between the two therapy cycles, bi-weekly 
tests of CBC, creatinine, and liver enzymes will be collected for three months. Within 10 
(+/- 5) days before administration of the second cycle, patients will be assessed for 
progression by history, clinical examination and repeat imaging studies (using the same 
imaging modality as for the pre-therapeutic imaging study). Patients with disease 
progression according to RECIST 1.1 will not receive a second cycle of 177Lu-DOTA- 
JR11. 
Patients with progression of disease between cycle 1 and 2 will be replaced. The activity 
of 177Lu-DOTA-JR11 administered per cycle will not exceed 200 mCi (7.4 GBq) 
independent from the radiation dose to the kidneys and/or red marrow. 
9.4 
Follow-up 
 
For each patient the same imaging modality (completed after cycle 1) will then be used 
for all follow-up imaging studies every 12 weeks. 
Patients will be monitored through bi-weekly tests of CBC, creatinine, and liver enzymes 
for three months after the second cycle and four to six weeks until all treatment-related 
toxicities have resolved, returned to baseline, or been deemed irreversible, whichever is 
longest. 
Urinalysis and LDH will be performed once every month to rule out thrombotic 
microangiopathy, and haptoglobin will be performed once every 2 months. 
Patients will then be followed by history and physical examination every 12 weeks with 
CT scan or MRI imaging (as is routine for metastatic NET patients at MSK). Uniform 
assessment of response will be provided for each patient, i.e. one patient may be 
followed by either MRI or triphasic CT, but not both. NET patients are infrequently lost to 
follow-up. However, should there be relocation, or if a patient chooses to be followed by 
their primary oncologist after the completion of the study, every effort will be made to 
identify the follow-up evaluation and ensure that all notes are sent to MSK. Patients will 
be contacted by telephone for at least one year (every three months) to determine 
disease-free survival and overall survival, and the investigators will obtain appropriate 
source documentation from external providers to corroborate these assessments. Every 
effort will be made to follow all patients for survival every three months until death, or the 
cut-off date for the last protocol-mandated analysis, whichever occurs first. Any patients 
deemed lost to follow up, proceed with another treatment or pass away while on-study, 
they will be taken off-study at that time. 
Patients removed from the study for unacceptable adverse events will be followed until 
resolution as well as for progression of disease. 
Patients receiving any portion of the therapeutic dose will be included in the assessment 
of response. 

Memorial Sloan Kettering Cancer Center 
IRB Number: 15-161 A(7) 
Approval date: 09-Sep-2020 
Page 24 of 39 
 
 
 
 
9.5 
Stopping Rules 
 
A 5% probability of excessive toxicities is considered acceptable and a 20% probability  
as unacceptable. Excessive toxicities are defined as treatment related toxicities leading 
to an unacceptable delay in completing the 2 cycles of therapy as well as any delayed or 
irreversible grade 3 or 4 toxicities. If we observe more than 1 excessive toxicity within the 
first 10 patients, we will stop the study. If not, we accrue 10 more patients for a total of  
20 patients. If we see more than 2 within the 20 (cumulative, including the 1 you might 
have seen among the first 10) we will also stop the study for excessive toxicity. If the true 
probability of toxicity is 5% then the probability of stopping for toxicity is 12%. If the true 
probability of toxicity is 20% then the probability of stopping for toxicity is 83%. 

Memorial Sloan Kettering Cancer Center 
IRB Number: 15-161 A(7) 
Approval date: 09-Sep-2020 
Page 25 of 39 
 
 
 
 
 
 
 
10.0 
EVALUATION DURING TREATMENT/INTERVENTION 
 
Schedule of Assessments 
 
Screening1 
PET/CT 
Dosimetry 
Treatment2 
Follow- 
up 
Every 3-4 
months 
Within 4 
weeks 
Within 2 
weeks 
Day 1 
Day 2-28 
Cycle 
1 
Cycle 
2 
At end of 
each cycle 
Informed consent 
X 
Medical history 
X 
X 
Physical exam 
X 
X3 
X3 
X 
Adverse event monitoring 
X16 
X16 
X 
X 
X 
Concomitant medications 
X 
X3 
X3 
ECOG/Karnofsky  status 
X 
X3 
X3 
Laboratory assessment 
X 
X3 
X3 
CBC, creatinine, and liver 
enzymes, urine analysis4 
X 
X 
Pregnancy test if applicable 
X 
X 
X 
X 
EKG 
X 
Urinalysis 
X 
X13 
Vital Signs 
X 
X5 
X5 
X5 
X5 
111In-Octreotide SPECT6 
X 
MRI/CT scan 
X 
X15 
X15 
68Ga-DOTA-JR11  injection 
X 
99mDTPA with filtration rate 
X 
X11 
X12 
68Ga-DOTA-JR11  PET/CT 
scan 
X 
177Lu-DOTA-JR11  injection7 
X 
X 
X 
Whole body imaging8 
X 
X 
X 
SPECT/CT9 
X 
X 
X 
Research blood draw10 
X 
X 
X 
Endocrine Monitoring 
X 
X 
X14 
Assessment for delayed 
toxicity (red bone marrow, 
renal and hepatic functions) 
X14 
1. To be completed prior to study entry, i.e. patient registration. 
2. Treatment with 177Lu-DOTA-JR11 will begin within 6 weeks of completion of dosimetrystudy; Cycle 1 and 2 will be 
performed 10-14 weeks apart. 
3. PE, ConMed review, performance status, and bloods (CBC, Comprehensive and LDH only) will be completed 7 -14 days 
prior to start of each cycle. 
4. Bi-weekly tests of CBC, creatinine, and liver enzymes for three months after each cycle. 
5. Vitals will be obtained prior to injections. 
6. Octreotide scan must be within 8 weeks prior to study entry. 
7. 177Lu-DOTA-JR11 injection will be given on Day 1. 
8. Whole body planar imaging will be obtained at nominal times of approximately1 -5 hours (i.e. day 1), 18-30 (i.e. day 2), 
66-120 (i.e. day 4-6), and 144-192 (i.e. day 7-9) hours post injection. Less than 20 min 
9. SPECT/CT will be obtained at 18-30 (day 2) hours post injection. Less than 40 min 
10. Research blood samples will be drawn at 5-10 min, 15-20 min, 30-40 min, 60-90 min, 120-150 min, and 4-6 hours post- 
injection and, subsequently, at the times of imaging. 
11. Within 2 weeks of cycle 2. 
12. Within 10-14 weeks after cycle 2 and within 11-13 months after the dosimetrystudy. 
13. Urinalysis and LDH will be performed every month. Haptoglobin will be performed every2 months. 
14. Within 11-13 months after the dosimetrystudy. 
15. The firs t imaging study(post-treatment baseline) will be performed within 10 (+/-5) days before start of cycle 2. In each 
patient the same imaging modality(CT or MRI) will be used for all follow-up imaging to ensure uniform response 
assessment. The first assessment of progression/response after completion of treatment will be performed 12 weeks after 

Memorial Sloan Kettering Cancer Center 
IRB Number: 15-161 A(7) 
Approval date: 09-Sep-2020 
Page 26 of 39 
 
 
 
 
 
the post-treatment baseline studyand subsequent assessments will again be performed at 12 week intervals, i.e. 12, 24, 
36, … weeks after the post-treatment baseline study. 
16. Please see section 11 for description of safety assessments. 
 
 
 
11.0 
TOXICITIES/SIDE EFFECTS 
 
Detection and Treatment of Infusion Reactions 
 
The following measures will be taken to detect and treat an infusion reaction: 
 
Nurses or physicians will monitor patients for the duration of the PET/CT, dosimetry and treatment 
periods. EKG and pulse oximetry will be continually monitored, and blood pressure measurements 
will be performed every 15-20 min.  For dosimetry and treatment monitoring will start with the 
infusion of the renal protectant solution and will be continued for total of approximately 4 h. Body 
temperature and blood glucose levels will be measured before the start of the infusion and 
approximately 4 h later. For the PET/CT study these measurements will be performed before 
injection and after completion of the imaging studies. 
To our knowledge, hypersensitivity reactions to somatostatin agonist or antagonists have not been 
reported in the literature. If the event of symptoms of a hypersensitivity reaction the patient will be 
treated the same way as an acute reaction to radiologic contrast media according to the guidelines 
of the Department of Radiology 
(https://one.mskcc.org/sites/pub/radiology/Documents/Contrast%20Reaction%20policy.pdf).   Briefly, 
mild to moderate reactions will be treated with diphenhydramine 25-50 mg PO or IV. Patients with a 
severe reaction will receive epinephrine 0.3 mg IM or 0.1-0.3 mg slowly IV. Patients will also receive 
oxygen via nasal cannula or face mask. 
In the unlikely event that the microdose of [68Ga] or [177Lu]-DOTA-JR11 causes a carcinoid 
syndrome, patients will be treated with octreotide and ranitidine. In the case of hypoglycemia in 
patients with an insulin secreting neuroendocrine tumor, glucose will be administered intravenously. 
All these drugs will be readily available at the time of radiopeptide therapy. 
Toxicity to Endocrine Glands 
 
Although somatostatin receptors are expressed by various endocrine glands, previous studies have 
not shown clinically significant effects after treatment with a cumulative dose of up to 800 mCi 177Lu- 
DOTA-TATE (31). In order to detect and monitor endocrine toxicities by 177Lu-DOTA-JR11 the 
following parameters will be determined before the dosimetry study, before the second treatment 
cycle, and 1 year after the dosimetry study: Serum gonadotropins (LH, FSH), estradiol, testosterone, 
free thyroxine (FT4), triiodothyronine (T3), thyroid-stimulating hormone (TSH), glycosylated 
hemoglobin (HBA1C) and ACTH as previously described for 177Lu-DOTA-TATE (31). HBA11C   will not 
be measured in patients who are diabetic at the time of inclusion into the study. An endocrinologist is 
an investigator of this study and any abnormalities will be discussed with the endocrinologist. 
Supplementation and/or management of the endocrine abnormalities (if any) will be under the 
discretion of the study endocrinologist. Since it is unlikely that alterations will be significant, no dose 
reductions are built into the protocol at the present time. Should we find consistent and/or significant 
abnormalities, we will inform our IRB, FDA and amend the protocol accordingly. 

Memorial Sloan Kettering Cancer Center 
IRB Number: 15-161 A(7) 
Approval date: 09-Sep-2020 
Page 27 of 39 
 
 
 
 
Assessment  for Delayed Toxicity 
 
Delayed toxicity assessment at one year will be conducted. Delayed effects on red bone marrow, 
renal and hepatic functions will be assessed (11-13 months after the dosimetry study) by patients’ 
interim history, physical examination, complete blood counts (white blood cell count with differential, 
hemoglobin, MCV, hematocrit, platelet count), serum creatinine and creatinine clearance with 
Cockcroft Gault formula, BUN, uric acid, albumin, bilirubin, AST, ALT, GGT, ALP, LDH, sodium 
potassium, calcium, glucose, and urinalysis). 
Risks 
 
68Ga-DOTA-JR11 PET/CT Scans 
 
As part of this scan, radiation is delivered both from the 68Ga and from the low-dose CT scan, which 
is performed as part of the PET/CT for attenuation correction and co-registration. Although any 
exposure to ionizing radiation has the potential to cause some harm to tissue, the radiation 
exposures in this study are comparable to the low-level exposures associated with common 
diagnostic procedures such as CT scanning. There remains a low theoretical risk of developing a 
cancer at some point later in life as a result of the radiation exposure received in this study. This risk 
is much smaller than the clinical risks posed by the patient’s current cancer. In general the radiation 
doses from the 68Ga-DOTA-JR11 PET/CT scan are much less (typically < 1%) of those from 177Lu- 
DOTA-JR11 therapy. 
177Lu-DOTA-JR11 Therapy 
 
Because of the low injected mass of the peptide (<= 100 µg), which is 1,000 times less than the 
therapeutic dose of somatostatin analogs (21), we do not expect pharmacologic effects by the 
peptide scaffold of DOTA-JR11. However, side effects may occur as a consequence of the beta and 
gamma radiation emitted by 177Lu. The toxicity of 177Lu-labeled DOTA-TATE, which has a similar 
biodistribution to 177Lu-DOTA-JR11 (10), has been studied in 504 patients with neuroendocrine 
tumors (3). Patients received up to 27.8-29.6 GBq (750 to 800 mCi), usually in four treatment cycles, 
with treatment intervals of 6 to 10 weeks. Hematologic toxicity grade 3 or 4 occurred after 3.6% of 
administrations. 62% of patients experienced grade 1 (i.e. minimal, per WHO criteria) temporary hair 
loss. Serious adverse events that were likely attributable to the treatment were myelodysplastic 
syndrome in three patients and temporary, nonfatal liver toxicity in two patients. There were two 
cases of renal insufficiency, but both were considered by the investigators to be unrelated to 177Lu- 
DOTA-TATE therapy. One patient with extensive liver metastases died of hepatic failure after five 
weeks of therapy. Because this patient experienced a similar deterioration due to rapid tumor growth 
after his previous course of chemotherapy, the liver failure was considered more likely tumor growth- 
related rather than radiation-induced. Two other patients, both of whom had multiple liver 
metastases, had temporary rises in serum ALT, AST, and bilirubin concentrations. In both patients, 
this condition resolved without causative treatment, and both resumed treatment at half doses 
uneventfully. Lastly, myelodysplastic syndrome (MDS) occurred in four patients. In one patient, 
previous chemotherapy with alkylating agents was the more likely cause of MDS. In the other three 
patients, MDS was diagnosed two to three years after the last treatment and was considered as 
probably treatment-related (3). 

Memorial Sloan Kettering Cancer Center 
IRB Number: 15-161 A(7) 
Approval date: 09-Sep-2020 
Page 28 of 39 
 
 
 
 
A higher rate of side effects has been observed in patients treated with the somatostatin analog 90Y- 
DOTA-TOC (2). A total of 1,109 patients were treated with two to four cycles of 3.7 GBq/m2 of 90Y- 
DOTA-TOC. Grade 3 or 4 hematologic toxicity was observed in 12.8% of the patients (n = 142). 
Leucopenia was observed in 67 patients, while anemia was observed in 11 patients, and 
thrombocytopenia in 64 patients. Of the total sample, 2 developed myeloproliferative syndromes, 
and 1 experienced acute myeloid leukemia. Another 2 patients developed tumor lysis syndrome 
directly after treatment with reversible kidney failure, and 102 patients (9.2%) experienced 
permanent renal toxicity (67 patients grade 4; 35 patients grade 5). The higher rate of renal toxicity 
is probably related to the higher energy of beta radiation emitted by 90Y, which leads to a higher 
radiation dose to the glomeruli (31). 
In the planned study, the risk of side effects will be minimized by performing detailed dosimetric 
studies for kidney and red marrow before and during therapy and by co-infusion of amino acids to 
decrease renal uptake of the JR11 (25). In a study of 90 patients treated with 90Y-DOTA-TOC (co- 
infused with Aminosyn II amino acid solution containing approximately 28 g of both lysine and 
arginine), temporary grade III/IV  renal toxicity was observed in 3 patients. No significant change in 
creatinine levels were observed at one year after the start of therapy (27). The amino acid infusion 
may cause nausea and vomiting. Other side effects are unlikely in the selected patient population 
with adequate renal and hepatic function. 

Memorial Sloan Kettering Cancer Center 
IRB Number: 15-161 A(7) 
Approval date: 09-Sep-2020 
Page 29 of 39 
 
 
 
 
JR11 
 
Preclinical Toxicology 
 
In mice, intravenous injection of 2,000 µg/kg did not cause death, a significant change in body 
weight, or pathologic findings on necropsy 15 days post-injection. 
Clinical Toxicology 
 
 
 
 
 
 
 
Table 6. Hematologic and clinical chemical parameters before and after treatment with 177Lu-DOTA- 
JR11 in four patients with metastatic neuroendocrine tumors (10). 
Four patients have so far been treated with 177Lu-DOTA-JR11 at a peptide mass of 160-200 µg per 
injection and an activity of 5.9-13.7 GBq. The activity was delivered with two to three injections per 
patient. One patient had one episode of flush after injection of 177Lu-DOTA-TATE, which resolved 
spontaneously. No other clinical side effects were observed. One episode of grade 3 
thrombocytopenia resolved within eight weeks after injection. Renal function showed no significant 
change during follow- 

Memorial Sloan Kettering Cancer Center 
IRB Number: 15-161 A(7) 
Approval date: 09-Sep-2020 
Page 30 of 39 
 
 
 
 
Radiation dosimetry 
 
The radiation exposure after injection of 177Lu-DOTA-JR11 has been measured in four patients with 
metastatic NETs (10) and is summarized in Table 5. Table 7 shows total radiation dose projections 
for the proposed study. The dose estimates used for 68Ga-DOTA-JR11 were generated by weighting 
published human radiation doses for 68Ga-DOTA-TATE (32) with the ratio of 68Ga-DOTA-JR11 to 
68Ga-DOTA-TATE tissue uptake in mice (7) . 
 
 
68Ga/177Lu-DOTA-JR11 Patient Dosimetry including CT 
 
 
Total Activity of 177Lu-DOTA-JR11 
12.74 
GBq in 3 admin = 
3441 
mCi 
 
 
SPECT/CT Attenuation scan@ 80mA 
0.9 
cGy x 3 
 
 
68Ga-DOTA-JR112 
177Lu-DOTA-JR113 
Dose from CT 
TOTAL 
Target Organ 
mGy/MBq 
cGy 
mGy/MBq 
cGy 
cGy 
cGy 
Kidney 
0.215 
3.98 
1.80 
2292 
3.6 
2300 
Liver 
0.057 
1.05 
0.33 
420 
3.6 
425 
Spleen 
0.097 
1.79 
3.00 
3821 
3.6 
3826 
Adrenal gland 
0.067 
1.24 
0.11 
140 
3.6 
145 
Lungs 
0.002 
0.04 
0.11 
140 
3.6 
144 
Urinary bladder wall 
0.100 
1.85 
0.37 
471 
3.6 
477 
Red marrow 
0.022 
0.41 
0.10 
127 
3.6 
131 
Total body 
0.013 
0.24 
0.13 
166 
3.6 
169 
Effective dose (rem) 
0.019 
0.35 
0.20 
255 
3.6 
259 
1 Please not that this is a typical activity. The exact administered activity will depend on the 
radiation dose calcluation as described in the text 
2  based on data for 68Ga-DOTATATE (Sandstrom et al,  J Nucl Med, 54, 1755-59, 2012) 
3 Wild et al. J Nucl Med, 55, 1248-52, 2014 
 
 
 
Table 7. Projected radiation dosimetry for the proposed clinical study. 
 
 
 
Reduction of the risk of radiation exposure to patient’s family member, the general public and 
health care workers 
Radiation dose rates measured in previous MSKCC pilot studies for patients administered 177Lu 
labeled compounds have shown average dose rates within an hour after administration to be 0.23 
mR/h/mCi (range 0.16-0.30) on contact and 0.011 mR/h/mCi (range 0.007-0.018) at a distance of 1 
m. Patient-specific instructions indicating how many days to implement radioactive precautions will 
be determined according to the limits of 10 CFR Part 35 (US Nuclear Regulatory Commission) using 
the methodology of NUREG-1556, Vol. 9, Appendix U (US Nuclear Regulatory Commission), and 
guidance in NCRP Report #155 (National Council on Radiation Protection and Measurements). 
MSKCC Radiation Safety staff will perform regulatory-required patient dose rate monitoring for each 
patient following administration and will prepare and provide patient-specific radioactive precautions 
Absorbed Dose Projections 
PET/CT Attenuation scan@ 80mA 
0.9 
cGy x 1 
Total Activity of 68Ga-DOTA-JR11 
185 
MBq in 1 admin = 
5 
mCi 

Memorial Sloan Kettering Cancer Center 
IRB Number: 15-161 A(7) 
Approval date: 09-Sep-2020 
Page 31 of 39 
 
 
 
 
in written and verbal form to each patient and the healthcare providers associated with the patient’s 
care. Patients will be required to acknowledge receipt of these instructions. The instructions will 
specify how long patients should sleep in a separate bed, when they are able to return work, how 
long to maximize distance from other adults, pregnant women and children, and how long to avoid 
extended time in public places. While in the medical facility, lead shielding (either permanent or 
portable) will be provided as required based on dose rate measurements to maintain dose rates at 1 
m from the patients to < 2 mR/h. 
 
 
12.0 
CRITERIA FOR THERAPEUTIC RESPONSE/OUTCOME ASSESSMENT 
 
Tumor response will be monitored by CT and MR studies acquired as part of routine standard 
clinical care of patients approximately three and six months after the last treatment cycle. Tumor 
response will be classified according to RECIST 1.1. Confirmatory scans for partial response will not 
be performed. Changes in tumor diameters for all lesions that can be well identified on the 
SPECT/CT images of the dosimetry study will be recorded and correlated with the calculated 
radiation doses. 
 
 
13.0 
CRITERIAFOR REMOVAL FROM STUDY 
 
Patients will go off-study if any of the following criteria are met: 
 
• 
Any treatment related CTCAE grade 4 toxicity 
• 
Unacceptable treatment delay due to delayed or irreversible toxicity 
• 
Patient request 
 
No replacement of patients discontinued for excessive toxicity is allowed. 
 
Participation in the study is strictly voluntary, and patients will have the right to withdraw from the 
study at any time. If a patient chooses to withdraw, he or she must inform the investigator 
immediately. In addition, the investigator has the right to terminate participation of any patient at any 
time if it is deemed in the patient’s best interest. Patients will be replaced if they are removed from 
the study and data obtained are inevaluable.  The reason and circumstances for premature 
discontinuation will be documented in the patient’s medical records. Possible examples for reasons 
of premature withdrawal include withdrawal of consent, SAE or intolerable AE, progression of 
disease, or any other medical illness at the investigator’s discretion. If a patient progresses between 
cycle 1 and 2, patient will be removed from the study. 
 
 
 
14.0 
BIOSTATISTICS 
Primary Objectives 
This is a first-in-man study of 68Ga-DOTA-JR11; there are only limited human data on the dosimetry 
of 177Lu-DOTA-JR11. The main goal is therefore to ensure safety and tolerability, and characterize 
the adverse event profile. In addition descriptive data on the diagnostic accuracy of 68Ga-DOTA- 

Memorial Sloan Kettering Cancer Center 
IRB Number: 15-161 A(7) 
Approval date: 09-Sep-2020 
Page 32 of 39 
 
 
 
 
JR11 and the tumor and normal organ doses after administration of 177Lu-DOTA-JR11 will be 
obtained. We expect an accrual rate of 1-2 patients per month. 
The safety, tolerability, and AE will be summarized using descriptive statistics. With 20 patients 
treated adverse event rates can be estimated to within +/- 10%, assuming the true rate is 25%, 
although estimation based on the observed data will use exact binomial confidence intervals and the 
length of confidence intervals will vary. All patients receiving a therapeutic dose of 177Lu-DOTA-JR11 
will be included in the safety data analysis. We will also capture those patients who do not receive a 
second therapeutic dose of 177Lu-DOTA-JR11 of and record the reasons for not proceeding to cycle 
2. 
Assessment of biodistribution will be descriptive by calculating the standardized uptake values and 
areas under the time activity curves for the two radiopharmaceuticals. 
Sensitivity of PET with 68Ga-DOTA-JR11 to stage metastatic NETs in comparison to the clinically 
used sstr agonist 111In-DTPA-octreotide will be assessed on a lesion basis. Reference standard will 
be determined by a consensus of the clinical investigators and systemic analysis of all available 
imaging studies and follow-up. Sensitivity will be estimated using the observed proportion of positive 
for a given modality using a variance inflation factor to adjust for multiple lesions in the same patient 
to compute the confidence intervals With an anticipated 4 lesions per patient and a putative 
intrapatient correlation of 0.1 these sensitivity can be estimated to within +/- 10%. 
177Lu-DOTA-JR11 dosimetry is described in Section 9.2. 
 
Secondary Objectives 
 
For estimation of radiation doses after administration of 177Lu-DOTA-JR11, we are assuming a 
standard deviation of 8.2 Gy/GBq for the tumor dose after the administration of 177Lu-DOTA-JR11 
and a standard deviation of 0.8 Gy/GBq for the kidney dose (as observed in our pilot study). Under 
these assumptions, we should be able to determine the tumor dose with a standard error of the 
mean of 1.83 Gy/GBq as well as the kidney dose with a standard error of the mean of 0.18 Gy/GBq. 
We consider these as sufficiently accurate for the planning of larger clinical studies. 
The correlation between tumor uptake of 68Ga-DOTA-JR11 and tumor dose of 177Lu-DOTA-JR11 will 
be estimated using rank-based methods (e.g. Spearman correlation) and reported in a descriptive 
way. 
Overall response rate (ORR) according to RECIST 1.1 and median progression-free and overall 
survival will be estimated and reported with 95% confidence intervals. As a measure of tumor 
response we will report the ORR at 6 months after administration of the second treatment cycle. 
We will generate Kaplan-Meier curves to describe and calculate the progression-free survival (PFS), 
which is defined as the period elapsing between the date of initiation of therapy and the date of  
either disease progression or date of death, whichever is earlier. This applies even if a given patient 
is withdrawn from treatment due to toxicity or discontinues treatment and is withdrawn prior to 
documentation of progression; all patients will be included in this statistic. We will also perform 
Kaplan-Meier curves to describe and calculate the overall survival (OS), defined as the interval 
between the time of initiation of therapy and the date of death from any cause. Patients who are 

Memorial Sloan Kettering Cancer Center 
IRB Number: 15-161 A(7) 
Approval date: 09-Sep-2020 
Page 33 of 39 
 
 
 
 
alive at the time of study completion will be censored at the time the patient was last known to be 
alive. 
Duration of stable disease (SD) will be summarized and measured from the start of treatment until 
the criteria for progression are met, taking as reference the smallest measurements recorded since 
the treatment started. All patients will be included in this analysis. A subset analysis of patients with 
stable disease at the initiation of therapy will be performed. 
Patients who progress between cycles 1 and 2 will be replaced. This is to ensure that we will be able 
to study toxicity and tolerability in 20 patients who finish full course of therapy. Patients who are 
replaced due to progression will still be included in the analysis of secondary endpoints (ORR, PFS 
and OS) so the sample size for some of the analyses may exceed 20. We expect progression during 
therapy to be rare. In a study of metastatic GEP-NETs treated with 177Lu-DOTA-TATE, progression 
during therapy occurred in only 37 out of 458 patients (8%) (3). 
 
 
15.1 
RESEARCH PARTICIPANT REGISTRATION AND RANDOMIZATION PROCEDURES 
 
15.2 
Research Participant Registration 
 
Confirm eligibility as defined in the section entitled Inclusion/Exclusion Criteria. Obtain 
informed consent, by following procedures defined in section entitled Informed Consent 
Procedures. During the registration process registering individuals will be required to 
complete a protocol specific Eligibility Checklist. The individual  signing the Eligibility Checklist 
is confirming that the participant is eligible to enroll in the study. Study staff are responsible 
for ensuring that all institutional requirements necessary to enroll a participant to the study 
have been completed. See related Clinical Research Policy and Procedure #401 (Protocol 
Participant Registration). 
15.3 
Randomization 
 
Not applicable. 
 
 
 
16.1 
DATA MANAGEMENT ISSUES 
 
A Clinical Research Coordinator (CRC) will be assigned to the study. The responsibilities of the CRC 
include project compliance, data collection, abstraction and entry, data reporting, regulatory 
monitoring, problem resolution and prioritization, and coordination of the protocol study team’s 
activities. 
The data collected for this study will be entered into a secure database. Source documentation will 
be available to support the computerized patient record. 
Study personnel will record clinical data in each patient’s source documents (i.e., the patient’s 
medical record). 

Memorial Sloan Kettering Cancer Center 
IRB Number: 15-161 A(7) 
Approval date: 09-Sep-2020 
Page 34 of 39 
 
 
 
 
The investigator will maintain adequate and accurate records to enable the conduct of the study to  
be fully documented and the study data to be subsequently verified. After study closure, the 
investigator will maintain all source documents, study-related documents, and the data stored in the 
database used for data collection. Records will be retained and securely stored for a minimum of two 
years after the completion of all study activities. 
Data will be entered throughout the duration of the trial as patients are enrolled. Accrual is expected 
to last 24 months. 
16.2 
Quality Assurance 
 
Regularly scheduled registration reports will be generated to monitor patient accruals and the 
completeness of registration data. Routine data quality reports will be generated to assess 
missing data and inconsistencies. Accrual rates and the extent and accuracy of evaluations 
and follow-up will be monitored periodically throughout the study period, and potential 
problems will be brought to the attention of the principal investigator for discussion and 
action. 
Random-sample data quality and protocol compliance audits will be conducted by the study 
team at least once a year, and more frequently if indicated. 
16.3 
Data and Safety Monitoring 
 
The data and safety monitoring (DSM) plans at MSK were approved by the National Cancer 
Institute (NCI) in September 2001. The plans address the policies set forth by the NCI in the 
document entitled Policy of the National Cancer Institute for Data and Safety Monitoring of 
Clinical Trials, which can be found at http://cancertrials.nci.nih.gov/clinicaltrials. The DSM 
plans at MSK were established and are monitored by the Office of Clinical Research. The 
MSK DSM plans can be found on the MSK Intranet at:  
https://one.mskcc.org/sites/pub/clinresearch/Documents/MSKCC%20Data%20and%20Safet  
y%20Monitoring%20Plans.pdf 
 
There are several different mechanisms by which clinical trials are monitored for data, safety, 
and quality. There are institutional processes in place for quality assurance (e.g., protocol 
monitoring, compliance and data verification audits, therapeutic response, and staff  
education on clinical research quality assurance) and departmental procedures for quality 
control, and two institutional committees are responsible for monitoring the activities of our 
clinical trials programs. The committees are as follows: Data and Safety Monitoring 
Committee (DSMC) for Phase I and II clinical trials, and the Data and Safety Monitoring 
Board (DSMB) for Phase III clinical trials; both of which report to the MSK Research Council 
and Institutional Review Board. 
During the protocol development and review process, each protocol will be assessed for its 
level of risk and degree of monitoring required. Every type of protocol (e.g., NIH-sponsored, 
in-house sponsored, industrial sponsored, NCI cooperative group, etc.) will be addressed, 
and the monitoring procedures will be established at the time of protocol activation. 

Memorial Sloan Kettering Cancer Center 
IRB Number: 15-161 A(7) 
Approval date: 09-Sep-2020 
Page 35 of 39 
 
 
 
 
17.1 
PROTECTION OF HUMAN SUBJECTS 
 
This study will be conducted in compliance with the protocol, GCP guidelines established by the 
International Conference on Harmonization, and the ethical standards set forth in the Declaration of 
Helsinki 2004 (available  at: www.laakariliitto.fi/e/ethics/helsinki.html). 
The PET/CT scan with 68Ga-DOTA-JR11 is diagnostic in nature and, based on our extensive clinical 
experience with diagnostic radiotracers in general and diagnostic radiolabeled peptides in particular, 
will involve administration of the labeled peptide at mass and activity levels far below those that 
would induce any toxic or other pharmacological effects. However, as with any exposure to radiation, 
even at the diagnostic levels to be used in this study, there is a very low, theoretical risk of radiation-
induced cancer at some later point in life. The projected normal-organ radiation doses to subjects in 
this study are determined and included in our protocols and are well in the range of typical 
diagnostic imaging tests for cancer patients, such as CT. The risk of subsequent radiation- induced 
cancer is explicitly included in the Informed Consent forms for the studies included in this protocol. 
In addition, the subjects who will be enrolled in this clinical investigation will be exclusively patients 
with metastatic neuroendocrine cancers. The additional radiation doses associated with the PET/CT 
scans involved in this study will typically represent a small increment in their "lifetime" exposures by 
diagnostic tests, and more importantly radiopeptide therapy. 
For the therapeutic part of the study, we also do not expect pharmacologic effects because the 
amount of peptide is again very low when compared to the therapeutic dose of somatostatin analogs 
(<= 100 µg every 3 months vs. 120 mg every 4 months). However, the therapeutic beta radiation 
presents a risk. Lutetium-177 has been extensively used for radiopeptide therapy of neuroendocrine 
tumors after coupling to the somatostatin agonist DOTA-TATE. Since the biodistribution and 
dosimetry of 177Lu-DOTA-JR11 is similar to 177Lu-DOTA-TATE (10) (Table 5), we therefore expect 
the same radiation exposure. 
17.2 
Privacy 
 
MSK’s Privacy Office may allow the use and disclosure of protected health information 
pursuant to a completed and signed Research Authorization form. The use and disclosure of 
protected health information will be limited to the individuals described in the Research 
Authorization form. A Research Authorization form must be completed by the Principal 
Investigator and approved by the IRB and Privacy Board (IRB/PB). 
 
The consent indicates that individualized  de identified information collected for the purposes 
of this study may be shared with other qualified researchers. Only researchers who have 
received approval from MSK will be allowed to access this information which will not include 
protected health information, such as the participant’s name, except for dates. It is also 
stated in the Research Authorization that their research data may be shared with other 
qualified  researchers. 
 
 
 
17.3 
Serious Adverse Event (SAE) Reporting 
 
An adverse event is considered serious if it results in ANY of the following outcomes: 

Memorial Sloan Kettering Cancer Center 
IRB Number: 15-161 A(7) 
Approval date: 09-Sep-2020 
Page 36 of 39 
 
 
 
 
• 
Death 
• 
A life-threatning adverse event 
• 
An adverse eent that results in inpatient hospitalization or prolongation of existing 
hospitalization 
• 
A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
• 
A congenital anomaly/birth defect 
• 
Important Medical Events (IME) that may not result in death, be life threatening, or 
require hospitalization may be considered serious when, based upon medical judgment, 
they may jeopardize the patient or subject and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition 
Note: Hospital adminssion for a planned procedure/disease treatment is not considered an 
SAE. 
 
SAE reporting is required as soon as the participant starts investigational 
treatment/intervention. SAE reporting is required for 30-days after the participant’s last 
investigational treatment or intervention. Any events that occur after the 30-day period and 
that are at least possibly related to protocol treatment must be reported. 
Please note: Any SAE that occurs prior to the start of investigational treatment/intervention 
and is related to a screening test or procedure (i.e., a screening biopsy) must be reported. 
 
All SAEs must be submitted in PIMS. If an SAE requires submission to the HRPP office per 
IRB SOP RR-408 ‘Reporting of Serious Adverse Events’, the SAE report must be submitted 
within 5 calendar days of the event.  All other SAEs must be submitted within 30 calendar 
days of the event. 
 
The report should contain the following information: 
 
• 
The date the adverse event occurred 
• 
The adverse event 
• 
The grade of the event 
• 
Relationship of the adverse event to the treatment(s) 
• 
If the AE was expected 
• 
Detailed text that includes the following 
o An explanation of how the AE was handled 
o A description of the participant’s condition 
o Indication if the participant remains on the study 
• 
If an amendment will need to be made to the protocol and/or consent form 
• 
If the SAE is an Unanticipated Problem 
 
 
 
17.2.1 
 
This protocol will have an IND. SAE will also be reported to the FDA through the IND office 
and the report will include the FDA-assigned IND number and name. 

Memorial Sloan Kettering Cancer Center 
IRB Number: 15-161 A(7) 
Approval date: 09-Sep-2020 
Page 37 of 39 
 
 
 
 
 
 
 
18.1 
INFORMED CONSENT PROCEDURES 
 
Before protocol-specified procedures are carried out, consenting professionals will explain 
the full details of the protocol and study procedures, as well as the risks involved to 
participants prior to their inclusion in the study. Participants will also be informed that they 
are free to withdraw from the study at any time. All participants must sign an IRB/PB- 
approved consent form indicating their consent to participate. This consent form meets the 
requirements of the Code of Federal Regulations and MSK’s Institutional Review 
Board/Privacy Board. The consent form will include the following: 
1. The nature and objectives, potential risks, and benefits of the intended study. 
2. The length of study and the likely follow-up required. 
3. Alternatives to the proposed study. (This will include available standard and 
investigational therapies. In addition, patients will be offered an option of supportive 
care for therapeutic studies). 
4. The name of the investigator(s) responsible for the protocol. 
5. The right of the participant to accept or refuse study interventions/interactions and to 
withdraw from participation at any time. 
Before any protocol-specific procedures can be carried out, the consenting professional will 
fully explain the aspects of patient privacy concerning research specific information. In 
addition to signing the IRB Informed Consent, all patients must agree to the Research 
Authorization component of the informed consent form. 
Each participant and consenting professional will sign the consent form. The participant must 
receive a copy of the signed informed consent form. 
 
 
19.0 
REFERENCES 
 
1. 
Otte A, Herrmann R, Heppeler A, Behe M, Jermann E, Powell P, Maecke HR, Muller J. 
Yttrium-90 DOTATOC: first clinical results. Eur J Nucl Med. 1999;26(11):1439-47.  PubMed PMID: 
10552085. 
2. 
Imhof A, Brunner P, Marincek N, Briel M, Schindler C, Rasch H, Macke HR, Rochlitz C, 
Muller-Brand J, Walter MA. Response, survival, and long-term toxicity after therapy with the 
radiolabeled somatostatin analogue [90Y-DOTA]-TOC in metastasized neuroendocrine cancers. J 
Clin Oncol. 2011;29(17):2416-23. PubMed PMID: 21555692. 
3. 
Kwekkeboom DJ, de Herder WW, Kam BL, van Eijck CH, van Essen M, Kooij PP, Feelders 
RA, van Aken MO, Krenning EP. Treatment with the radiolabeled somatostatin analog [177 Lu- 
DOTA 0,Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol. 2008;26(13):2124-30. PubMed 
PMID: 18445841. 
4. 
Ambrosini V, Fani M, Fanti S, Forrer F, Maecke HR. Radiopeptide imaging and therapy in 
Europe. J Nucl Med. 2011;52 Suppl 2:42S-55S. PubMed PMID: 22144555. 
5. 
Moll S, Nickeleit V, Mueller-Brand J, Brunner FP, Maecke HR, Mihatsch MJ. A new cause of 
renal thrombotic microangiopathy: yttrium 90-DOTATOC internal radiotherapy. Am J Kidney Dis. 
2001;37(4):847-51. PubMed PMID: 11273886. 
6. 
Ginj M, Zhang H, Waser B, Cescato R, Wild D, Wang X, Erchegyi J, Rivier J, Macke HR, 
Reubi JC. Radiolabeled somatostatin receptor antagonists are preferable to agonists for in vivo 

Memorial Sloan Kettering Cancer Center 
IRB Number: 15-161 A(7) 
Approval date: 09-Sep-2020 
Page 38 of 39 
 
 
 
 
 
peptide receptor targeting of tumors. Proc Natl Acad Sci U S A. 2006;103(44):16436-41. PubMed 
PMID: 17056720. 
7. 
Fani M, Braun F, Waser B, Beetschen K, Cescato R, Erchegyi J, Rivier JE, Weber WA, 
Maecke HR, Reubi JC. Unexpected sensitivity of sst2 antagonists to N-terminal radiometal 
modifications. J Nucl Med. 2012;53(9):1481-9. Epub 2012/08/02. doi: 10.2967/jnumed.112.102764. 
PubMed PMID: 22851637. 
8. 
Fani M, Del Pozzo L, Abiraj K, Mansi R, Tamma ML, Cescato R, Waser B, Weber WA, Reubi 
JC, Maecke HR. PET of somatostatin receptor-positive tumors using 64Cu- and 68Ga-somatostatin 
antagonists: the chelate makes the difference. J Nucl Med. 2011;52(7):1110-8. Epub 2011/06/18. 
doi: 10.2967/jnumed.111.087999.  PubMed PMID: 21680701. 
9. 
Wild D, Fani M, Behe M, Brink I, Rivier JE, Reubi JC, Maecke HR, Weber WA. First clinical 
evidence that imaging with somatostatin receptor antagonists is feasible. J Nucl Med. 
2011;52(9):1412-7. PubMed PMID: 21852357. 
10. 
Wild D, Fani M, Fischer R, Del Pozzo L, Kaul F, Krebs S, Rivier JE, Reubi JC, Maecke HR, 
Weber WA. Comparison of Somatostatin Receptor Agonist and Antagonist for Peptide Receptor 
Radionuclide Therapy: A Pilot Study. J Nucl Med. 2014;55(8):1248-52. Epub 2014/06/26. doi: 
10.2967/jnumed.114.138834.  PubMed PMID: 24963127. 
11. 
Cescato R, Waser B, Fani M, Reubi JC. Evaluation of 177Lu-DOTA-sst2 antagonist versus 
177Lu-DOTA-sst2 agonist binding in human cancers in vitro. J Nucl Med. 2011;52(12):1886-90. 
Epub 2011/11/10. doi: 10.2967/jnumed.111.095778.  PubMed PMID: 22068898. 
12. 
Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64(1):9-29. 
Epub 2014/01/09. doi: 10.3322/caac.21208. PubMed PMID: 24399786. 
13. 
Markman M, Levin M, Reilly P, Coyne JW, Lammersfeld C, Birdsall TC. Assuring dietary 
supplement quality for cancer patients: An integrated formulary systems approach. J Clin Oncol. 
2013;31(15). PubMed PMID:  WOS:000335419605066. 
14. 
Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, Abdalla EK, Fleming JB, 
Vauthey JN, Rashid A, Evans DB. One hundred years after "carcinoid": epidemiology of and 
prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 
2008;26(18):3063-72. PubMed PMID: 18565894. 
15. 
Graham MM, Menda Y. Radiopeptide imaging and therapy in the United States. J Nucl Med. 
2011;52 Suppl 2:56S-63S. Epub 2011/12/22. doi: 10.2967/jnumed.110.085746.  PubMed PMID: 
22144556. 
16. 
Oberg K, Akerstrom G, Rindi G, Jelic S. Neuroendocrine gastroenteropancreatic tumours: 
ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21 
Suppl 5:v223-7. PubMed PMID: 20555086. 
17. 
Reubi JC, Kvols LK, Waser B, Nagorney DM, Heitz PU, Charboneau JW, Reading CC, 
Moertel C. Detection of somatostatin receptors in surgical and percutaneous needle biopsy samples 
of carcinoids and islet cell carcinomas. Cancer Res. 1990;50(18):5969-77. PubMed PMID: 2168286. 
18. 
Waser B, Tamma ML, Cescato R, Maecke HR, Reubi JC. Highly efficient in vivo agonist- 
induced internalization of sst2 receptors in somatostatin target tissues. J Nucl Med. 2009;50(6):936- 
41. PubMed PMID: 19443580. 
19. 
Weckbecker G, Lewis I, Albert R, Schmid HA, Hoyer D, Bruns C. Opportunities in 
somatostatin research: biological, chemical and therapeutic aspects. Nat Rev Drug Discov. 
2003;2(12):999-1017. PubMed PMID: 14654798. 
20. 
Rinke A, Muller HH, Schade-Brittinger C, Klose KJ, Barth P, Wied M, Mayer C, Aminossadati 
B, Pape UF, Blaker M, Harder J, Arnold C, Gress T, Arnold R. Placebo-controlled, double-blind, 
prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in 
patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group. J 
Clin Oncol. 2009;27(28):4656-63. PubMed PMID: 19704057. 
21. 
Caplin ME, Pavel M, Cwikla JB, Phan AT, Raderer M, Sedlackova E, Cadiot G, Wolin EM, 
Capdevila J, Wall L, Rindi G, Langley A, Martinez S, Blumberg J, Ruszniewski P. Lanreotide in 
metastatic enteropancreatic neuroendocrine tumors. N Engl J Med. 2014;371(3):224-33. Epub 
2014/07/12. doi: 10.1056/NEJMoa1316158.  PubMed PMID: 25014687. 

Memorial Sloan Kettering Cancer Center 
IRB Number: 15-161 A(7) 
Approval date: 09-Sep-2020 
Page 39 of 39 
 
 
 
 
 
22. 
Schirmer WJ, Melvin WS, Rush RM, O'Dorisio TM, Pozderac RV, Olsen JO, Ellison EC. 
Indium-111-pentetreotide  scanning versus conventional imaging techniques for the localization of 
gastrinoma. Surgery. 1995;118(6):1105-13; discussion 13-4. PubMed PMID: 7491530. 
23. 
Reidy-Lagunes DL, Gollub MJ, Saltz LB. Addition of octreotide functional imaging to cross - 
sectional computed tomography or magnetic resonance imaging for the detection of neuroendocrine 
tumors: added value or an anachronism? J Clin Oncol. 2011;29(3):e74-5. PubMed PMID: 21079131. 
24. 
Reubi JC, Schar JC, Waser B, Wenger S, Heppeler A, Schmitt JS, Macke HR. Affinity 
profiles for human somatostatin receptor subtypes SST1-SST5 of somatostatin radiotracers selected 
for scintigraphic and radiotherapeutic use. Eur J Nucl Med. 2000;27(3):273-82. PubMed PMID: 
10774879. 
25. 
Bodei L, Cremonesi M, Zoboli S, Grana C, Bartolomei M, Rocca P, Caracciolo M, Macke HR, 
Chinol M, Paganelli G. Receptor-mediated radionuclide therapy with 90Y-DOTATOC in association 
with amino acid infusion: a phase I study. Eur J Nucl Med Mol Imaging. 2003;30(2):207-16. PubMed 
PMID: 12552338. 
26. 
Valkema R, Pauwels S, Kvols LK, Barone R, Jamar F, Bakker WH, Kwekkeboom DJ, 
Bouterfa H, Krenning EP. Survival and response after peptide receptor radionuclide therapy with 
[90Y-DOTA0,Tyr3]octreotide in patients with advanced gastroenteropancreatic neuroendocrine 
tumors. Semin Nucl Med. 2006;36(2):147-56. PubMed PMID: 16517236. 
27. 
Bushnell DL, Jr., O'Dorisio TM, O'Dorisio MS, Menda Y, Hicks RJ, Van Cutsem E, Baulieu 
JL, Borson-Chazot F, Anthony L, Benson AB, Oberg K, Grossman AB, Connolly M, Bouterfa H, Li Y, 
Kacena KA, LaFrance N, Pauwels SA. 90Y-edotreotide for metastatic carcinoid refractory to 
octreotide. J Clin Oncol. 2010;28(10):1652-9. PubMed PMID: 20194865. 
28. 
Gabriel M, Decristoforo C, Kendler D, Dobrozemsky G, Heute D, Uprimny C, Kovacs P, Von 
Guggenberg E, Bale R, Virgolini IJ. 68Ga-DOTA-Tyr3-octreotide PET in neuroendocrine tumors: 
comparison with somatostatin receptor scintigraphy and CT. J Nucl Med. 2007;48(4):508-18. 
PubMed PMID: 17401086. 
29. 
Srirajaskanthan R, Kayani I, Quigley AM, Soh J, Caplin ME, Bomanji J. The role of 68Ga- 
DOTATATE PET in patients with neuroendocrine tumors and negative or equivocal findings on 
111In-DTPA-octreotide scintigraphy. J Nucl Med. 2010;51(6):875-82. Epub 2010/05/21. doi: 
10.2967/jnumed.109.066134.  PubMed PMID: 20484441. 
30. 
Velikyan I, Sundin A, Sorensen J, Lubberink M, Sandstrom M, Garske-Roman U, Lundqvist 
H, Granberg D, Eriksson B. Quantitative and qualitative intrapatient  comparison of 68Ga-DOTATOC 
and 68Ga-DOTATATE: net uptake rate for accurate quantification. J Nucl Med. 2014;55(2):204-10. 
Epub 2014/01/01. doi: 10.2967/jnumed.113.126177.  PubMed PMID: 24379222. 
31. 
Konijnenberg M, Melis M, Valkema R, Krenning E, de Jong M. Radiation dose distribution in 
human kidneys by octreotides in peptide receptor radionuclide therapy. J Nucl Med. 2007;48(1):134- 
42. PubMed PMID: 17204710. 
32. 
Sandstrom M, Velikyan I, Garske-Roman U, Sorensen J, Eriksson B, Granberg D, Lundqvist 
H, Sundin A, Lubberink M. Comparative biodistribution and radiation dosimetry of 68Ga-DOTATOC 
and 68Ga-DOTATATE in patients with neuroendocrine tumors. J Nucl Med. 2013;54(10):1755-9. 
PubMed PMID: 23929824. 
 
 
 
 
20.0 
APPENDICES 
 
Not applicable.