Evaluation of 68Ga-Exendin-4 PET/CT Imaging for Detection of Paragangliomas in Patients

The primary objective of this study is to evaluate the **feasibility** of detecting paragangliomas (PGLs) using 68Ga-exendin-4 PET/CT. This is clinically relevant as it aims to establish a novel imaging technique that could potentially improve the diagnostic accuracy for PGLs, a rare type of neuroendocrine tumor.

Secondary objectives include:

• Determining the optimal timepoint for imaging PGLs using 68Ga-exendin-4 PET/CT.
• Comparing semi-quantitative imaging parameters, such as standardized uptake value (SUV), tumor-to-background ratio, and contrast-to-noise ratio, between 68Ga-exendin-4 PET/CT and SSTR PET/CT.
• Assessing the correlation between GLP-1R expression and tracer uptake in PGLs.
• Correlating quantitative imaging results with immunohistochemistry (IHC) data.
• Assessing the safety and side effects of 68Ga-exendin-4 in patients with PGLs.

The clinical trial involves participants diagnosed with **paragangliomas**, aiming to assess the feasibility of detecting these tumors using 68Ga-exendin-4 PET/CT. The study population includes both male and female subjects, with an age range encompassing adults and older adults. The trial does not focus on a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants were selected based on specific criteria, including having a proven sympathetic paraganglioma with a single tumor detected through standard diagnostic imaging, no evidence of metastatic disease, and being scheduled for surgery. All participants must be able to sign informed consent. The trial does not specify any particular lifestyle considerations such as diet or physical activity.

The clinical trial is designed to evaluate the feasibility of detecting **paragangliomas** using 68Ga-exendin-4 PET/CT imaging. This is a phase IV, randomized, double-blind, controlled study. The trial is expected to commence on December 22, 2021, and conclude by February 22, 2025. Participants will be involved in the study for a maximum treatment period of one day, with the primary endpoint being the detection rate of paragangliomas using the specified imaging technique. Secondary endpoints include determining the optimal timepoint for imaging, comparing quantitative imaging parameters, and correlating GLP-1R expression with tracer uptake.

The study will begin with an inclusion visit, where participants will be screened based on criteria such as having a proven sympathetic paraganglioma with a single tumor detected via standard diagnostic imaging, no evidence of metastatic disease, and being scheduled for surgery. Participants must also be able to provide informed consent. Follow-up visits will be scheduled to monitor the imaging process and collect data on the primary and secondary endpoints. The end-of-study visit will involve a final assessment of the imaging results and any correlations with genetic data.

Participants may be terminated early from the study if they do not meet the inclusion criteria, if there is evidence of metastatic disease, or if they are unable to comply with the study protocol. The study will utilize **exenatide** administered via intravenous bolus injection or IV infusion, with a maximum daily dose of 100 MBq. The trial aims to provide valuable insights into the imaging of paragangliomas, potentially improving diagnostic accuracy and patient outcomes.

The clinical trial involves the use of **exenatide**, an investigational medication, for the imaging of paragangliomas using PET/CT technology. **Exenatide** is a synthetic peptide, also known by its synonyms **exendin-4**, LY-2148568, HIS-GLY-GLU-GLY-THR-PHE-THR-SER-ASP-LEU-SER-LYS-GLN-MET-GLU-GLU-GLU-ALA-VAL-ARG-LEU-PHE-ILE-GLU-TRP-LEU-LYS-ASN-GLY-GLY-PRO-SER-SER-GLY-ALA-PRO-PRO-PRO-SER-NH2, and AC-2993. The pharmaceutical form of **exenatide** used in this study is designated as PHF00231MIG. The medication is administered via **intravenous bolus injection/IV infusion**. The maximum daily dose and total dose amount are both set at 100 MBq megabecquerel(s), with a maximum treatment period of one day. The formulation includes a C-terminal modification with Lys, and a chelator NODAGA is attached via an AHX spacer for labeling with Ga68, enhancing its imaging capabilities.

In this trial, **exenatide** is the primary investigational product, and no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The study does not involve a pediatric formulation, and the investigational product is classified as an orphan drug, with the designation number EMA/OD/0000028068. Participant compliance with the dosing schedule is monitored to ensure adherence to the protocol. The trial aims to assess the feasibility of detecting paragangliomas using 68Ga-exendin-4 PET/CT, with **exenatide** serving as the test substance in this imaging study.

Efficacy in this clinical trial will be assessed primarily through the **detection rate of paragangliomas (PGLs)** using 68Ga-exendin-4 PET/CT imaging. This primary endpoint will evaluate the ability of the imaging technique to identify PGLs effectively. Secondary endpoints include determining the optimal timepoint for imaging PGLs with 68Ga-exendin-4 PET/CT, comparing quantitative imaging parameters such as standardized uptake value (SUV), tumor-to-background ratio, and contrast-to-noise ratio between the optimal timepoint, 18F-FDG PET, and SSTR PET. Additionally, the study will assess the correlation between GLP-1R expression and tracer uptake in PGLs, as well as the correlation of quantitative imaging results and immunohistochemistry (IHC) data with the genetic origin of the PGLs.