Application of ⁶⁸Ga-FXX489 (NNS309) PET/CT Imaging in Diagnosis of Tumor Diseases.
Phase: PHASE1
Conditions: Tumor, Metastatic Cancer
Sponsor: Yi Tian

Version Number: 1.0
Version Date: 25 July 2025
Application of ⁶⁸Ga-FXX489 (NNS309) Imaging in the Diagnosis of Tumour
Diseases
I. Basic Project Information:
Self-selected research topic, prospective study, project duration: 1 August 2025 to 31
July 2027.
II. Research Background:
Tumours represent a major threat to human health. In the management of cancer
patients, 18F-FDG PET/CT serves as a valuable imaging modality, though certain
limitations warrant attention. Firstly, 18F-FDG PET/CT occasionally demonstrates
reduced sensitivity in detecting primary tumour lesions, owing to significant
variations in 18F-FDG uptake across different tumour histological types. Secondly, its
low to moderate sensitivity in lymph node staging limits its utility for tumour staging
and surgical planning. Furthermore, 18F-FDG PET occasionally demonstrates
reduced sensitivity for primary or metastatic tumours in organs such as the liver and
brain. Consequently, developing an effective PET tracer holds promise for enhancing
tumour detection and facilitating personalised patient care. Fibroblast activation
protein is overexpressed in tumour-associated fibroblasts, which constitute the
primary component of the epithelial tumour stroma. Consequently, a novel radiotracer,
⁶⁸Ga-FXX489 (NNS309), has been developed to target fibroblast activation protein
and visualise the tumour stroma. It exhibits favourable in vivo pharmacokinetics and
biodistribution, enabling clear delineation of both primary tumours and their
metastases. Phase I studies of [⁶⁸Ga]Ga-FXX489 (NNS309) and [¹⁷⁷Lu]Lu-FXX489
(NNS309) are currently underway in patients with pancreatic, lung, breast, and
colorectal cancers. Units undertaking the clinical application of the ⁶⁸Ga-FXX489
(NNS309) imaging agent must possess a Class IV licence for the use of
radiopharmaceuticals. Our department currently holds the requisite qualifications to

undertake this work and is positioned to pioneer the implementation of this
technology.
III. Research Objectives:
The objective of this study is to investigate the diagnostic value of ⁶⁸Ga-FXX489
(NNS309) imaging in oncological diseases.
IV. Research Tools
General
Information
Questionnaire:
A
questionnaire
for
collecting
general
demographic data on study subjects was designed independently through literature
review. It included: patient age, gender, educational attainment, marital status,
occupation, and current medical history.V. Study Population
Prospective collection of case records from 80 patients newly diagnosed with or
treated for oncological conditions at the First Affiliated Hospital of China Medical
University between 1 August 2025 and 31 July 2027, who underwent ⁶⁸Ga-FXX489
(NNS309) and ⁶⁸Ga-FAP-2286 PET/CT examinations.
Inclusion Criteria: 1-2 are mandatory requirements
1. Patients with a high suspicion of neoplastic disease;
2. Age: 18-80 years, no gender restrictions, able to express themselves independently,
willing to participate in this study and sign the informed consent form.
Exclusion Criteria: 1-6 are mandatory exclusion requirements
1. Failure to sign the informed consent form;
2. Patients with severe visual or hearing impairment, cognitive impairment, or
claustrophobia unable to communicate effectively;
3. Severe cardiac insufficiency, NYHA class III–IV;
4. Renal failure (serum creatinine > 1.2 mg/dl);
5. Individuals with alcohol allergy;
6. Use of medications within one week prior to examination that may induce a

disulfiram-like reaction with alcohol,
such as penicillins, cephalosporins, or
cephamycins.
Exclusion criteria:
1. Participants unable to complete the examination and forced to discontinue the trial
prematurely;
2. Subjects requesting withdrawal from the clinical trial;
3. Images rendered unusable for clinical diagnosis due to non-equipment-related
factors such as subject movement during scanning or leakage of radiopharmaceutical.
VI. Clinical Research Instruments, Equipment and Premises
1. Siemens Biograph MCT PET/CT positron emission and X-ray computed
tomography imaging equipment;
2. The research project was conducted in the Nuclear Medicine PET/CT Department
of the First Affiliated Hospital of China Medical University.
VII. Clinical Research Methods
(I) Clinical Research Process
1. Prior to study commencement, subjects undergo preliminary screening to identify
those meeting inclusion criteria and exclude ineligible candidates. Selected subjects
sign informed consent forms, typically completed by the subject themselves. In
exceptional circumstances, a designated proxy may sign on the subject's behalf.
2. The investigator recorded relevant clinical information (e.g., subject age, serum
biomarkers, or tumour-related symptoms) and equipment operational status.
3. ⁶⁸Ga-FXX489 (NNS309) and ⁶⁸Ga-FAP-2286 were produced in-house by this
department. Drug synthesis utilised GE's cyclotron, with radiochemical purity
exceeding 95%.
The ⁶⁸Ga-FXX489 (NNS309) and ⁶⁸Ga-FAP-2286 PET/CT imaging equipment
comprises Siemens Biograph MCT PET/CT positron emission and X-ray computed
tomography systems. No specific preparations (such as fasting or normal blood

glucose levels) are required on the day of the PET/CT examination. Prior to the scan,
administer ⁶⁸Ga-FXX489 (NNS309) intravenously at a dose of 1.8–2.2 MBq/kg.
Following administration, instruct the patient to rest, drink plenty of fluids, and
urinate frequently. [0.05–0.06 mCi]/kg intravenously. Following administration,
patients are instructed to rest, drink ample fluids, urinate frequently, and empty their
bladder prior to imaging. PET/CT scanning commences 60 minutes later with the
patient raising both arms above their head, arms pressed against the ears, breathing
calmly. The scan range extends from the top of the head to the groin. Low-dose CT:
120 kV, 120 mA·s scan. Matrix: 512×512. Slice thickness: 5 mm. PET/CT acquisition:
5–6 gantry positions, 2–3 minutes per position.
4. Reconstruction methods for ⁴⁶⁸Ga-FXX489 (NNS309) and ⁶⁸Ga-FAP-2286 PET/CT
imaging: TrueX+TOF (ultraHD-PET) with 3 iterations and 21 subsets. Image fusion
was performed via the Xeleris workstation to generate coronal, sagittal, and transverse
CT, PET, and PET/CT fusion images.
5. Both ⁶⁸Ga-FXX489 (NNS309) and ⁶⁸Ga-FAP-2286 images were randomly
interpreted by physicians with over 10 years' experience in nuclear oncology.
Disagreements were resolved by consensus. Lesions exhibiting uptake above the
visually identifiable background were considered positive. Regions of interest were
manually delineated for semi-quantitative analysis. The maximum standardised
uptake value (SUVmax) was automatically calculated by the dominant workstation to
quantify tracer uptake in primary tumours, involved lymph nodes, and distant
metastases. SUVmax, median standard uptake value, and range were recorded.
6. Statistics and Analysis: All data analysis was performed using SPSS (version 22.0;
IBM, Amonk, New York). Visual interpretation of PET/CT images was compared
with histopathological findings (biopsy or surgical specimens) as the reference
standard. The sensitivity, specificity, and accuracy of ⁶⁸Ga-FXX489 (NNS309) and
⁶⁸Ga-FAP-2286 PET/CT examinations were calculated, with diagnostic performance
evaluated using the McNemar test. A two-tailed t-test with P < 0.05 was considered
statistically significant.

(II) Quality Control in Clinical Research
Throughout this study, all participating personnel must undergo standardised training,
employing uniform recording methods and assessment criteria. The entire clinical
research process shall be conducted under strict operational protocols. Investigators
shall complete the General Information Questionnaire truthfully, thoroughly, and
conscientiously, ensuring all entries are complete, accurate, and reliable. All
observations and findings within the research project shall be verified to guarantee
data
reliability,
ensuring
that
conclusions
are
derived
from
original
data.
Corresponding data management measures shall be implemented during both the
project execution and data processing phases.
VIII. Evaluation Methods and Statistical Analysis for Clinical Research
Evaluation of Equipment and Medications: Technicians and nurses operating the
equipment and administering medications shall conduct assessments, with summary
statistics compiled upon trial completion.
Image Quality Evaluation: Obtained images shall be assessed by physicians holding
the title of Attending Physician or above within the Nuclear Medicine Department,
employing a triple-blind evaluation approach.
Statistical Processing Methods: Statistical analysis shall be conducted using SPSS
22.0 statistical software, with receiver operating characteristic curves plotted for
subjects.