This clinical research evaluates a new PET/CT imaging agent, \[68Ga\]Ga-HBED-CC-PEG6-exendin-4, for localizing insulinoma, a rare pancreatic tumor that causes severe low blood sugar. Insulinomas are often small and hard to detect with regular CT, ultrasound or standard PET scans. This new tracer targets GLP1R, a protein highly expressed on insulinoma cells, with polyethylene glycol (PEG6) modification to improve tumor uptake and image contrast compared with the earlier similar agent \[68Ga\]Ga-HBED-CC-exendin-4.
The investigators plan to enroll 20 adult patients suspected of or confirmed to have insulinoma. All participants will receive two free PET/CT scans within one week: one with the new PEG6-modified tracer and one with the original tracer. The first 3 participants will also get dynamic PET scanning to analyze drug distribution and radiation dose in the human body. Within one month after imaging, patients will undergo surgery or biopsy to get pathological results, which serve as the gold standard to calculate and compare the diagnostic accuracy of the two tracers.
All imaging procedures follow standard clinical protocols with safe, low radiation doses within national diagnostic limits. Minor possible risks include slight pain or mild allergic reaction at the injection site; rare side effects related to exendin-4 may occur at a rate below 5%, and the research team has full emergency management measures ready. Participants can withdraw from the study at any time without penalty. All scan fees are covered by the research project, and each subject will receive a formal imaging report for clinical reference. The findings of this trial will help develop a more accurate imaging tool to precisely locate insulinoma and guide surgical treatment.
Age between 18 and 70 years, male or female.
Clinically suspected insulinoma with biochemically proven endogenous hyperinsulinism.
Complete clinical information and conventional abdominal imaging data available.
Scheduled for pancreatic surgery or biopsy within 30 days after PET/CT examination for pathological confirmation.
Pregnancy, suspected pregnancy, or lactating status.
Severe hepatic or renal dysfunction prohibiting radiotracer injection.
Known allergy or hypersensitivity to exendin-4, gallium-based tracers, or injection excipients.
Uncontrolled severe systemic diseases that preclude PET/CT acquisition.
Single group
[68Ga]Ga-HBED-CC-PEG6-exendin-4 PET/CT
Diagnostic testInvestigational GLP-1R-targeted radiopharmaceutical modified with a PEG6 linker. Synthesized under mild 50 °C, 5 min one-step radiolabeling without purification, with radiochemical purity \>95% for up to two half-lives. Intravenous dose 1-4 mCi for whole-body PET/CT. The first 3 enrolled subjects receive dynamic PET acquisition to calculate human pharmacokinetic profiles and internal organ radiation dosimetry. Preclinical data confirmed elevated pancreatic and insulinoma uptake and improved pancreas-to-kidney ratio compared with non-PEGylated reference tracer.
[68Ga]Ga-HBED-CC-exendin-4 PET/CT
Diagnostic testReference GLP-1R-targeted radiopharmaceutical without PEG6 modification, serving as the control agent for head-to-head comparison. Prepared via one-step mild radiolabeling with no purification needed. Intravenous injection of 1-4 mCi followed by standard static PET/CT, completed within 7 days before or after the investigational tracer scan in each subject. Exhibits relatively higher renal background uptake that may interfere with visualization of left peri-renal insulinoma lesions. No dynamic PET acquisition is performed for this reference tracer.
Diagnostic performance comparison between two GLP-1R PET tracers for insulinoma localization
sensitivity of \[68Ga\]Ga-HBED-CC-PEG6-exendin-4 and \[68Ga\]Ga-HBED-CC-exendin-4 PET/CT.
Diagnostic performance comparison between two GLP-1R PET tracers for insulinoma localization
specificity of \[68Ga\]Ga-HBED-CC-PEG6-exendin-4 and \[68Ga\]Ga-HBED-CC-exendin-4 PET/CT.
Diagnostic performance comparison between two GLP-1R PET tracers for insulinoma localization
accuracy of \[68Ga\]Ga-HBED-CC-PEG6-exendin-4 and \[68Ga\]Ga-HBED-CC-exendin-4 PET/CT.
Diagnostic performance comparison between two GLP-1R PET tracers for insulinoma localization
PPV of \[68Ga\]Ga-HBED-CC-PEG6-exendin-4 and \[68Ga\]Ga-HBED-CC-exendin-4 PET/CT.
Comparison of tumor-to-background ratios of the two GLP-1R radiotracers
Measure lesion SUV, tumor-to-background ratio (TBR) on PET/CT images of \[68Ga\]Ga-HBED-CC-PEG6-exendin-4 and reference tracer to compare image contrast and background interference.
Comparison of renal uptake of the two GLP-1R radiotracers
Measure renal semi-quantitative uptake on PET/CT images of \[68Ga\]Ga-HBED-CC-PEG6-exendin-4 and reference tracer to compare image contrast and background interference.
Area under plasma radioactivity concentration-time curve (AUC0-t)
Dynamic PET data from the first 3 participants are used to calculate in vivo biodistribution parameters and organ radiation absorbed dose of the PEG6-modified investigational tracer.
Internal radiation dosimetry of [68Ga]Ga-HBED-CC-PEG6-exendin-4
Dynamic PET data from the first 3 participants are used to calculate in vivo biodistribution parameters and organ radiation absorbed dose of the PEG6-modified investigational tracer.
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