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

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...

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Autores principales:	Takaaki Murakami, Hiroyuki Fujimoto, Keita Hamamatsu, Yuki Yamauchi, Yuzo Kodama, Naotaka Fujita, Junji Fujikura, Yoichi Shimizu, Yuji Nakamoto, Hiroyuki Kimura, Hideo Saji, Nobuya Inagaki
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/eb79b0bd544f428e86385fa7f2a8e030
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spelling	oai:doaj.org-article:eb79b0bd544f428e86385fa7f2a8e0302021-12-02T17:55:03ZDistinctive detection of insulinoma using [18F]FB(ePEG12)12-exendin-4 PET/CT10.1038/s41598-021-94595-62045-2322https://doaj.org/article/eb79b0bd544f428e86385fa7f2a8e0302021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94595-6https://doaj.org/toc/2045-2322Abstract 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.Takaaki MurakamiHiroyuki FujimotoKeita HamamatsuYuki YamauchiYuzo KodamaNaotaka FujitaJunji FujikuraYoichi ShimizuYuji NakamotoHiroyuki KimuraHideo SajiNobuya InagakiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Takaaki Murakami Hiroyuki Fujimoto Keita Hamamatsu Yuki Yamauchi Yuzo Kodama Naotaka Fujita Junji Fujikura Yoichi Shimizu Yuji Nakamoto Hiroyuki Kimura Hideo Saji Nobuya Inagaki Distinctive detection of insulinoma using [18F]FB(ePEG12)12-exendin-4 PET/CT
description	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.
format	article
author	Takaaki Murakami Hiroyuki Fujimoto Keita Hamamatsu Yuki Yamauchi Yuzo Kodama Naotaka Fujita Junji Fujikura Yoichi Shimizu Yuji Nakamoto Hiroyuki Kimura Hideo Saji Nobuya Inagaki
author_facet	Takaaki Murakami Hiroyuki Fujimoto Keita Hamamatsu Yuki Yamauchi Yuzo Kodama Naotaka Fujita Junji Fujikura Yoichi Shimizu Yuji Nakamoto Hiroyuki Kimura Hideo Saji Nobuya Inagaki
author_sort	Takaaki Murakami
title	Distinctive detection of insulinoma using [18F]FB(ePEG12)12-exendin-4 PET/CT
title_short	Distinctive detection of insulinoma using [18F]FB(ePEG12)12-exendin-4 PET/CT
title_full	Distinctive detection of insulinoma using [18F]FB(ePEG12)12-exendin-4 PET/CT
title_fullStr	Distinctive detection of insulinoma using [18F]FB(ePEG12)12-exendin-4 PET/CT
title_full_unstemmed	Distinctive detection of insulinoma using [18F]FB(ePEG12)12-exendin-4 PET/CT
title_sort	distinctive detection of insulinoma using [18f]fb(epeg12)12-exendin-4 pet/ct
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/eb79b0bd544f428e86385fa7f2a8e030
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Distinctive detection of insulinoma using [18F]FB(ePEG12)12-exendin-4 PET/CT

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