Glucagon-Like Peptide-1 Receptor PET/CT with ⁶⁸Ga-NOTA-Exendin-4 for Detecting Localized Insulinoma: A Prospective Cohort Study

Abstract

Preoperative localization of insulinoma is a clinical dilemma. We aimed to investigate whether glucagon-like peptide-1 receptor (GLP-1R) PET/CT with 68Ga-NOTA-MAL-cys40-exendin-4 (68Ga-NOTA-exendin-4) is efficient in detecting insulinoma. Methods In our prospective cohort study, patients with endogenous hyperinsulinemic hypoglycemia were enrolled. CT, MRI, endoscopic ultrasound, and 99mTc-hydrazinonicotinamide-TOC SPECT/CT were done according to standard protocols. GLP-1R PET/CT was performed 30–60 min after the injection of 68Ga-NOTA-exendin-4. The gold standard for diagnosis was the histopathologic results after surgery. Results Of 52 recruited patients, 43 patients with histopathologically proven insulinomas were included for the imaging studies. Nine patients did not undergo surgical intervention. 68Ga-NOTA-exendin-4 PET/CT correctly detected insulinomas in 42 of 43 patients with high tumor uptake (mean SUVavg ± SD, 10.2 ± 4.9; mean SUVmax ± SD, 23.6 ± 11.7), resulting in sensitivity of 97.7%. In contrast, 99mTc-hydrazinonicotinamide-TOC SPECT/CT showed a low sensitivity of 19.5% (8/41) in this group of patients; however, it successfully localized the tumor that was false-negative with GLP-1R PET/CT. The sensitivities of CT, MR, and endoscopic ultrasonography were 74.4% (32/43), 56.0% (14/25), and 84.0% (21/25), respectively. Conclusion 68Ga-NOTA-exendin-4 PET/CT is a highly sensitive imaging technique for the localization of insulinoma.

Clinical Value of 18F-FDOPA PET/CT With Contrast Enhancement and Without Carbidopa Premedication in Patients with Insulinoma

“…GLP1 analogs have recently been shown to possess great sensitivity in the detection of insulinomas (20,21). Furthermore, in a prospective multicentric study conducted by Christ et al,using 111 In-diethylenetriaminepentaacetic acid-exendin-4 for single-photon-emission CT examination, a transient exacerbation of hypoglycemia was reported (20).…”

“…A large, prospective cohort study by Luo et al, using 68 Galabeled exendin-4 derivative, also showed promising sensitivity for PET/CT when compared to other imaging modalities. High uptake in the kidneys, however, necessitated further imaging 2 to 3 h after injection in some cases (21).…”

Localisation of occult extra‐pancreatic insulinoma using glucagon‐like peptide‐1 receptor molecular imaging

“…6 Recently updated scatter correction protocols have reduced this problem, but if observed it can be resolved through re-processing PET data without use of 'scatter correction'.…”

“…6 GLP1 negative cases are typically avid on SSTR imaging. 5,6 Halo reconstruction artefact (i.e. suppression of background activity adjacent to regions of intense uptake) is a known limitation of PET 'scatter correction' algorithms.…”

PET Imaging for Endocrine Malignancies: From Woe to Go

“…Recent studies have shown that radiolabeled somatostatin receptor antagonists are preferable to agonists for in vivo peptide receptor targeting, and there are several ongoing studies across various NETs. Glucagon-like peptide-1 receptor imaging using 68 Ga-exendin-4 PET/CT (15) and 18 F-radiolabeled analogs of exendin-4 PET/CT has emerged and is highly sensitive for detecting benign insulinomas that might be missed by other imaging studies (16). Studies have also shown a high expression of C-X-C chemokine receptor type 4 in normal adrenal cortex and adrenocortical tumors, opening new avenues for imaging these tumors with peptides targeting C-X-C chemokine receptor type 4 ( 68 Ga-pentixafor) and theranostic approaches (17,18).…”