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

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

doi:10.1038/s41598-021-94595-6

Cited by 13 publications

(26 citation statements)

References 42 publications

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“…Thus, further investigation with longer-term evaluation using our GIP -/- mice is required for elucidating the beneficial effects of GIP for consequential prevention of type 2 diabetes mellitus. Finally, positron emission tomography imaging with GLP-1R-targeted probes may provide better image resolution and higher sensitive information on BCM changes ( 9 , 13 ).…”

Section: Discussionmentioning

confidence: 99%

“…Recently, pancreatic b-cell-specific imaging using nuclear medicine techniques has been developed (10). In particular, exendin-based glucagon-like peptide-1 receptor (GLP-1R)-targeted imaging has emerged as a promising tool for noninvasive evaluation of BCM (9,(11)(12)(13)(14)(15). An indium 111 ( 111 In)-labeled exendin-4 derivative ([Lys 12 ( 111 In-BnDTPA-Ahx)]exendin-4) targeting GLP-1R has been developed (9,16) that enables longitudinal analysis of BCM changes in living mice by quantification of pancreatic uptake of 111 In-exendin-4 on single-photon emission computed tomography/computed tomography (SPECT/CT) images (9,17).…”

Section: Introductionmentioning

confidence: 99%

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Noninvasive Evaluation of GIP Effects on β-Cell Mass Under High-Fat Diet

et al. 2022

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Pancreatic β-cell mass (BCM) has an importance in the pathophysiology of diabetes mellitus. Recently, glucagon-like peptide-1 receptor (GLP-1R)-targeted imaging has emerged as a promising tool for BCM evaluation. While glucose-dependent insulinotropic polypeptide/gastric inhibitory polypeptide (GIP) is known to be involved in high-fat diet (HFD)-induced obesity, the effect of GIP on BCM is still controversial. In this study, we investigated indium 111 (111In)-labeled exendin-4 derivative ([Lys12(111In-BnDTPA-Ahx)]exendin-4) single-photon emission computed tomography/computed tomography (SPECT/CT) as a tool for evaluation of longitudinal BCM changes in HFD-induced obese mice, at the same time we also investigated the effects of GIP on BCM in response to HFD using GIP-knockout (GIP-/-) mice. 111In-exendin-4 SPECT/CT was able to distinguish control-fat diet (CFD)-fed mice from HFD-fed mice and the pancreatic uptake values replicated the BCM measured by conventional histological methods. Furthermore, BCM expansions in HFD-fed mice were demonstrated by time-course changes of the pancreatic uptake values. Additionally, 111In-exendin-4 SPECT/CT demonstrated the distinct changes in BCM between HFD-fed GIP-/- (GIP-/-+HFD) and wild-type (WT+HFD) mice; the pancreatic uptake values of GIP-/-+HFD mice became significantly lower than those of WT+HFD mice. The different changes in the pancreatic uptake values between the two groups preceded those in fat accumulation and insulin resistance. Taken together with the finding of increased β-cell apoptosis in GIP-/-+HFD mice compared with WT+HFD mice, these data indicated that GIP has preferable effects on BCM under HFD. Therefore, 111In-exendin-4 SPECT/CT can be useful for evaluating increasing BCM and the role of GIP in BCM changes under HFD conditions.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Noninvasive Evaluation of GIP Effects on β-Cell Mass Under High-Fat Diet

et al. 2022

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“…This study reports the results of the first-in-human PET study with [ 18 F]FB(ePEG12)12-exendin-4 ( 18 F-Ex4) ( 19 ), a novel exendin probe labeled with fluorine-18 ( 18 F). The purpose of this study is to demonstrate the clinical safety, whole-body distribution, and dose estimation of the probe in healthy subjects, as well as to show the clinical utility for human pancreas imaging by PET.…”

Section: Introductionmentioning

confidence: 99%

First-in-Human Evaluation of Positron Emission Tomography/Computed Tomography With [18F]FB(ePEG12)12-Exendin-4: A Phase 1 Clinical Study Targeting GLP-1 Receptor Expression Cells in Pancreas

et al. 2021

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Pancreatic β-cell mass (BCM) has a central importance in the pathophysiology of diabetes mellitus. Recently, pancreatic β-cell-specific imaging, especially positron emission tomography (PET) with exendin-based probes, has emerged for non-invasive evaluation of BCM. We developed a novel exendin-based probe labeled with fluorine-18, [18F]FB(ePEG12)12-exendin-4 (18F-Ex4) for PET imaging. We subsequently conducted a first-in-human phase 1 study of 18F-Ex4 PET/computed tomography (CT) and investigated the safety and utility for visualizing the pancreas. Six healthy male subjects were enrolled in this study. A low dose (37.0 MBq) of 18F-Ex4 PET/CT was administered (first cohort: n = 2), and subsequently a higher dose (74.0 MBq) was administered (second cohort: n = 4). In the first and second cohorts, 38.6 ± 4.8 and 71.1 ± 4.8 MBq of 18F-Ex4 were administered, respectively. No serious adverse events were observed in both groups. Only one participant in the first cohort showed transient hypoglycemia during the PET scans. 18F-Ex4 PET/CT successfully visualized the pancreas in all participants. The mean standardized uptake value of the pancreas was found to be higher than that in the surrounding organs, except for the bladder and kidney, during the observation. Dosimetry analyses revealed the effective systemic doses of 18F-Ex4 as 0.0164 ± 0.0019 mSv/MBq (first cohort) and 0.0173 ± 0.0020 mSv/MBq (second cohort). 18F-Ex4 PET/CT demonstrated the safety and utility for non-invasive visualization of the pancreas in healthy male subjects. 18F-Ex4 is promising for clinical PET imaging targeting pancreatic β cells.

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“…Approximately 0.37 MBq of 111 In exendin‐4 was added, followed by incubation for 30 min on ice. The islets were washed using chilled phosphate‐buffered saline, and radioactivity was measured in an auto‐well γ‐counter (Wallac 1480 WIZARD 3″ γ‐counter, PerkinElmer, Inc., Waltham, MA, USA), as previously described 24 . The results were expressed as radioisotope counts per minute from islets after 30 min of incubation.…”

Section: Methodsmentioning

confidence: 99%

Noninvasive quantitative evaluation of viable islet grafts using ¹¹¹In‐exendin‐4 SPECT/CT

et al. 2023

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Islet transplantation (IT) is an effective βcell replacement therapy for patients with type 1 diabetes; however, the lack of methods to detect islet grafts and evaluate their βcell mass (BCM) has limited the further optimization of IT protocols. Therefore, the development of noninvasive βcell imaging is required. In this study, we investigated the utility of the 111 Indium-labeled exendin-4 probe {[Lys12(111In-BnDTPA-Ahx)] exendin-4} ( 111 In exendin-4) to evaluate islet graft BCM after intraportal IT. The probe was cultured with various numbers of isolated islets. Streptozotocin-induced diabetic mice were intraportally transplanted with 150 or 400 syngeneic islets. After a 6-week observation following IT, the exvivo liver graft uptake of 111 In-exendin-4 was compared with the liver insulin content. In addition, the in-vivo liver graft uptake of 111 In exendin-4 using SPECT/CT was compared with that of liver graft BCM measured by a histological method. As a result, probe accumulation was significantly correlated with islet numbers. The ex-vivo liver graft uptake in the 400-islet-transplanted group was significantly higher than that in the control and the 150-islet-transplanted groups, consistent with glycemic control and liver insulin content. In conclusion, in-vivo SPECT/ CT displayed liver islet grafts, and uptakes were corroborated by histological liver

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

Cited by 13 publications

References 42 publications

Noninvasive Evaluation of GIP Effects on β-Cell Mass Under High-Fat Diet

Noninvasive Evaluation of GIP Effects on β-Cell Mass Under High-Fat Diet

First-in-Human Evaluation of Positron Emission Tomography/Computed Tomography With [18F]FB(ePEG12)12-Exendin-4: A Phase 1 Clinical Study Targeting GLP-1 Receptor Expression Cells in Pancreas

Noninvasive quantitative evaluation of viable islet grafts using ¹¹¹In‐exendin‐4 SPECT/CT

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

Cited by 13 publications

References 42 publications

Noninvasive Evaluation of GIP Effects on β-Cell Mass Under High-Fat Diet

Noninvasive Evaluation of GIP Effects on β-Cell Mass Under High-Fat Diet

First-in-Human Evaluation of Positron Emission Tomography/Computed Tomography With [18F]FB(ePEG12)12-Exendin-4: A Phase 1 Clinical Study Targeting GLP-1 Receptor Expression Cells in Pancreas

Noninvasive quantitative evaluation of viable islet grafts using 111In‐exendin‐4 SPECT/CT

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Noninvasive quantitative evaluation of viable islet grafts using ¹¹¹In‐exendin‐4 SPECT/CT