PT  - JOURNAL ARTICLE
AU  - Kimura, Hiroyuki
AU  - Matsuda, Hirokazu
AU  - Ogawa, Yu
AU  - Toyoda, Kentaro
AU  - Kon, Asami
AU  - Ono, Masahiro
AU  - Inagaki, Nobuya
AU  - Saji, Hideo
TI  - Evaluation of newly synthesized <sup>68</sup>Ga-labeled Exendin-4 derivative targeting glucagon-like peptide-1 receptor
DP  - 2013 May 01
TA  - Journal of Nuclear Medicine
PG  - 444--444
VI  - 54
IP  - supplement 2
4099  - http://jnm.snmjournals.org/content/54/supplement_2/444.short
4100  - http://jnm.snmjournals.org/content/54/supplement_2/444.full
SO  - J Nucl Med2013 May 01; 54
AB  - 444 Objectives Insulinoma is a tumor derived from a pancreatic β-cell, and it is a disease with the hypoglycemia due to the hyperinsulinoma. Recent studies have reported frequent overexpression of glucagon-like peptide-1 receptor (GLP-1R) in human insulinomas. So, a radiolabeled compound bound to GLP-1R has been expected to be useful for imaging insulinoma. In addition, GLP-1R is a promising molecule for pancreatic β-cell imaging. Exendin-4 is the natural peptide mimetic of GLP-1. In this study, we synthesized 68Ga-labeled Exendin-4 ([68Ga]Df12-Ex4) targeting GLP-1R, and evaluated its utility as a probe for PET imaging of insulinoma. Methods The binding affinity of Ga-Df12-Ex4 to human GLP-1R was evaluated by competitive binding assay using the prepared membranes. Biodistribution studies were carried out in INS-1 xenografted mice. PET imaging was carried out in INS-1 xenografted mice. In addition, stability of [68Ga]Df12-Ex4 in vivo was evaluated by analysis of the extracted tumor homogenate with reverse phase HPLC analysis. Results Ga-Df12-Ex4 had high affinity for GLP-1R (IC50 = 17 nM). The in vivo biodistribution of [67Ga]Df12-Ex4 in INS-1 xenografted mice showed a high uptake in the tumor (30 %ID/g at 1 hr) and high tumor-to-blood (T/B), tumor-to-muscle (T/M), and tumor-to-pancreas (T/P) ratios (T/B = 9.8, T/M = 51, T/P = 1.8 at 1 hr). Preadministration of excess nonradioactive exendin(9-39) significantly reduced accumulation in the tumor and the pancreas (83% and 94% inhibition, respectively) at 1hr after [67Ga]Df12-Ex4 injection, indicating that major fractions of the uptakes of [67Ga]Df12-Ex4 in the tumor and pancreas were mediated by the GLP-1R. PET studies with [68Ga]Df12-Ex4 in mice showed the clear image of the tumor 30 min after injection. In addition, [68Ga]Df12-Ex4 showed high stability in vivo. Conclusions We demonstrated that a newly synthesized [68Ga]Df12-Ex4 has a potential as imaging probe targeting for insulionma.