Glucagon-Like Peptide-1 Receptor–Targeted PET/CT With 68Ga-HBED-CC-Exendin-4 in Localizing Insulinoma

Purpose Modifying glucagon-like peptide-1 receptor (GLP-1R)–targeted PET agent to achieve faster renal clearance and preserved high affinity to GLP-1R is clinically relevant. The aim of this study is to assess the performance of a newly developed GLP-1R–targeted agent, 68 Ga-HBED-CC-exendin-4 in localizing insulinoma, and its biodistribution, as compared with previously introduced 68 Ga-NOTA-exendin-4. Patients and Methods Nineteen patients with endogenous hyperinsulinemic hypoglycemia were enrolled and referred for 68 Ga-HBED-CC-exendin-4 PET/CT and 68 Ga-NOTA-exendin-4 PET/CT within 2 consecutive days. Diagnostic performance of the 2 tracers in localizing insulinoma was evaluated, and SUV of the lesion, normal pancreas background, kidneys, and bladder were measured. Results 68 Ga-HBED-CC-exendin-4 and 68 Ga-NOTA-exendin-4 PET/CT exhibited an equivalent efficacy in detection rate (both sensitivity of 100%). Although SUV max of the tumor in 68 Ga-HBED-CC-exendin-4 was significantly lower than that in 68 Ga-NOTA-exendin-4 (20.01 ± 9.41 vs 31.78 ± 15.46, P < 0.001) at 50 minutes postinjection, there was no significant difference in the tumor-to-background ratio between the 2 agents (8.61 ± 3.57 vs 8.18 ± 3.38, P = 0.326), and the lesions could be visible as early as 4 minutes postinjection for both agents in patients who underwent dynamic PET/CT. In addition, 68 Ga-HBED-CC-exendin-4 exhibited approximately 30% decrease of the renal accumulation compared with 68 Ga-NOTA-exendin-4 (SUV mean , 42.21 ± 5.79 vs 58.58 ± 10.06 at 50 minutes, P < 0.001). Conclusions 68 Ga-HBED-CC-exendin-4 is an effective agent for localizing insulinoma showing similar detectability and tumor-to-background ratio compared with 68 Ga-NOTA-exendin-4. Notably, 68 Ga-HBED-CC-exendin-4 exhibits significantly lower renal uptake than 68 Ga-NOTA-exendin-4, which might potentially benefit the detection of the tumors adjacent to the left kidneys.