GLP-1 receptor antagonist as a potential probe for pancreatic {beta}-cell imaging

Journal Article · Fri Nov 20 04:00:00 EST 2009 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2009.09.014· OSTI ID:22199885

Mukai, Eri ^[1]; Toyoda, Kentaro ^[1]; Kimura, Hiroyuki ^[2]; Kawashima, Hidekazu ^[3]; Fujimoto, Hiroyuki ^[1]; Ueda, Masashi ^[4]; Temma, Takashi ^[2]; Hirao, Konomu; Nagakawa, Kenji ^[5]; Saji, Hideo ^[2]; Inagaki, Nobuya ^[1]

---

1. Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Kyoto (Japan)
2. Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto (Japan)
3. Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Kyoto (Japan)
4. Radioisotopes Research Laboratory, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto (Japan)
5. Research and Development Division, Arkray, Inc., Kyoto (Japan)

We examined exendin(9-39), an antagonist of glucagon-like peptide-1 (GLP-1) receptor (GLP-1R), as a potential probe for imaging of pancreatic {beta}-cells. To evaluate in vitro receptor specificity, binding assay was performed using dispersed mouse islet cells. Binding assay showed competitive inhibition of [{sup 125}I]BH-exendin(9-39) binding by non-radioactive exendin(9-39). To assess in vivo selectivity, the biodistribution was evaluated by intravenous administration of [{sup 125}I]BH-exendin(9-39) to mice. Radioactivity of harvested pancreas reached highest levels at 60 and 120 min among organs examined except lung. Pre-administration of excess non-radioactive exendin(9-39) remarkably and specifically blocked the radioactivity of pancreas. After [{sup 125}I]BH-exendin(9-39) injection into transgenic mice with pancreatic {beta}-cells expressing GFP, fluorescent and radioactive signals of sections of pancreas were evaluated with an image analyzer. Imaging analysis showed that the fluorescent GFP signals and the radioactive signals were correspondingly located. Thus, the GLP-1R antagonist exendin(9-39) may serve as a useful probe for pancreatic {beta}-cell imaging.

• OSTI ID: 22199885
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 389; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
FLUORESCENCE
GLUCAGON
IMAGES
IN VITRO
IN VIVO
IODINE 125
LUNGS
PANCREAS
PROBES
RADIOACTIVITY
RECEPTORS
TRANSGENIC MICE