Distinctive detection of insulinoma using [18F]FB(ePEG12)12-exendin-4 PET/CT

Takaaki Murakami; Hiroyuki Fujimoto; Keita Hamamatsu; Yuki Yamauchi; Yuzo Kodama; Naotaka Fujita; Junji Fujikura; Yoichi Shimizu; Yuji Nakamoto; Hiroyuki Kimura; Hideo Saji; Nobuya Inagaki

doi:10.1038/s41598-021-94595-6

Distinctive detection of insulinoma using [¹⁸F]FB(ePEG12)12-exendin-4 PET/CT

Sci Rep. 2021 Jul 22;11(1):15014. doi: 10.1038/s41598-021-94595-6.

Authors

Affiliations

¹ Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
² Radioisotope Research Center, Agency of Health, Safety and Environment, Kyoto University, Kyoto, Japan.
³ Department of Gastroenterology, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki, Japan.
⁴ Department of Gastroenterology, Graduate School of Medicine, Kobe University, Kobe, Japan.
⁵ Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
⁶ Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, Kyoto, Japan.
⁷ Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
⁸ Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan. inagaki@kuhp.kyoto-u.ac.jp.

Abstract

Specifying the exact localization of insulinoma remains challenging due to the lack of insulinoma-specific imaging methods. Recently, glucagon-like peptide-1 receptor (GLP-1R)-targeted imaging, especially positron emission tomography (PET), has emerged. Although various radiolabeled GLP-1R agonist exendin-4-based probes with chemical modifications for PET imaging have been investigated, an optimal candidate probe and its scanning protocol remain a necessity. Thus, we investigated the utility of a novel exendin-4-based probe conjugated with polyethylene glycol (PEG) for [¹⁸F]FB(ePEG12)12-exendin-4 PET imaging for insulinoma detection. We utilized [¹⁸F]FB(ePEG12)12-exendin-4 PET/CT to visualize mouse tumor models, which were generated using rat insulinoma cell xenografts. The probe demonstrated high uptake value on the tumor as 37.1 ± 0.4%ID/g, with rapid kidney clearance. Additionally, we used Pdx1-Cre;Trp53^R172H;Rb^f/f mice, which developed endogenous insulinoma and glucagonoma, since they enabled differential imaging evaluation of our probe in functional pancreatic neuroendocrine neoplasms. In this model, our [¹⁸F]FB(ePEG12)12-exendin-4 PET/CT yielded favorable sensitivity and specificity for insulinoma detection. Sensitivity: 30-min post-injection 66.7%, 60-min post-injection 83.3%, combined 100% and specificity: 30-min post-injection 100%, 60-min post-injection 100%, combined 100%, which was corroborated by the results of in vitro time-based analysis of internalized probe accumulation. Accordingly, [¹⁸F]FB(ePEG12)12-exendin-4 is a promising PET imaging probe for visualizing insulinoma.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line, Tumor
Disease Models, Animal
Fluorine Radioisotopes*
Insulinoma / diagnostic imaging*
Insulinoma / pathology
Male
Mice
Mice, Transgenic
Positron Emission Tomography Computed Tomography / methods*
Positron-Emission Tomography / methods
Radiopharmaceuticals*
Rats
Xenograft Model Antitumor Assays

Substances

Fluorine Radioisotopes
Radiopharmaceuticals