Localization of Hidden Insulinomas with ⁶⁸Ga-DOTA-Exendin-4 PET/CT: A Pilot Study

Abstract

111 In-DOTA-exendin-4 SPECT/CT has been shown to be highly efficient in the detection of insulinomas. We aimed at determining whether novel PET/CT imaging with [Nle 14 ,Lys 40 (Ahx-DOTA-68 Ga) NH 2 ]exendin-4 ( 68 Ga-DOTA-exendin-4) is feasible and sensitive in detecting benign insulinomas. Methods: 68 Ga-DOTA-exendin-4 PET/CT and 111 In-DOTA-exendin-4 SPECT/CT were performed in a randomized cross-over order on 5 patients with endogenous hyperinsulinemic hypoglycemia. The gold standard for comparison was the histologic diagnosis after surgery. Results: In 4 patients histologic diagnosis confirmed a benign insulinoma, whereas one patient refused surgery despite a positive 68 Ga-DOTA-exendin-4 PET/CT scan. In 4 of 5 patients, previously performed conventional imaging (CT or MR imaging) was not able to localize the insulinoma. 68 Ga-DOTA-exendin-4 PET/CT correctly identified the insulinoma in 4 of 4 patients, whereas 111 In-DOTA-exendin-4 SPECT/CT correctly identified the insulinoma in only 2 of 4 patients. Conclusion: These preliminary data suggest that the use of 68 Ga-DOTA-exendin-4 PET/CT in detecting hidden insulinomas is feasible.

Approaches to Improve the Pharmacokinetics of Radiolabeled Glucagon-Like Peptide-1 Receptor Ligands Using Antagonistic Tracers

“…Despite these efforts and successful translation of agonistic SPECT (4,5,7) and PET (8,13,15) tracers into the clinic, further improvements may be required to lower the extremely high kidney uptake of radiometal-based peptides, which complicates the detection of insulinomas in the head and tail of the pancreas and poses a potential radiation safety hazard. In addition, the release of insulin stimulated by low-specific-activity agonists and concomitant hypoglycemia complicates clinical studies and could be a safety issue.…”

“…Naturally occurring GLP-1 receptor agonist GLP-1(7-36)NH 2 was used as an internal reference, and agonist [Nle 14 ,Lys 40 (Ahx-DOTA-68 Ga)NH 2 ]Ex-4, validated for insulinoma imaging in patients (15), was used as a reference for biodistribution studies ( Table 1). The lowest IC 50 values were found for the 2 agonists [Nle 14 ,Lys 40 (Ahx-DOTA)NH 2 ]Ex-4 (0.9 6 0.3 nmol/L) and GLP-1(7-36)NH 2 (1.1 6 0.3 nmol/L).…”

“…Peptides were radiolabeled with 68 Ga using a 68 Ga/Ge generator with a radiochemical purity of more than 98% and specific activity of 15 …”

“…Therefore, imaging probes for optical (2), bimodal (3), SPECT (4-7), and PET (8-13) imaging as well as MRI (14) were developed to localize GLP-1 receptors preoperatively and in addition to determine b-cell mass in diabetic animal models and potentially in patients. In particular, SPECT (4,5,7) and PET (8,13,15) agents were successfully translated into the clinic, and several promising clinical studies were reported. Still, there are a few shortcomings with the available tracers.…”

Radiopeptides for Imaging and Therapy: A Radiant Future

“…Recently, 68 Ga-labeled exendin-4 has been introduced in the clinic for the detection of GLP-1 receptor-positive insulinomas (6). 68 Ga-DOTA-exendin-4 PET/ CT is preferred over 111 In-DOTA-exendin-4 SPECT/CT because of the higher spatial resolution and better quantification options obtained with PET/CT cameras.…”