Visualization of biodistribution of Zn complex with antidiabetic activity using semiconductor Compton camera GREI

Masayuki Munekane; Shinji Motomura; Shinichiro Kamino; Masashi Ueda; Hiromitsu Haba; Yutaka Yoshikawa; Hiroyuki Yasui; Makoto Hiromura; Shuichi Enomoto

doi:10.1016/j.bbrep.2015.12.004

Visualization of biodistribution of Zn complex with antidiabetic activity using semiconductor Compton camera GREI

Biochem Biophys Rep. 2015 Dec 8:5:211-215. doi: 10.1016/j.bbrep.2015.12.004. eCollection 2016 Mar.

Authors

Masayuki Munekane^{1

2}, Shinji Motomura³, Shinichiro Kamino^{1

3}, Masashi Ueda¹, Hiromitsu Haba⁴, Yutaka Yoshikawa⁵, Hiroyuki Yasui⁵, Makoto Hiromura³, Shuichi Enomoto^{1

3}

Affiliations

¹ Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushimanaka, Kita-ku, Okayama 700-8530, Japan.
² Japan Society for the Promotion of Science, 5-3-1 Kojimachi, Chiyoda-ku, Tokyo 102-0083, Japan.
³ Next-generation Imaging Team, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
⁴ RIKEN Nishina Center for Accelerator-Based Science, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
⁵ Department of Analytical and Bioinorganic Chemistry, Division of Analytical and Physical Chemistry, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.

Abstract

Various types of zinc (Zn) complexes have been developed as promising antidiabetic agents in recent years. However, the pharmacological action of Zn complex is not elucidated because the biodistribution of the complex in a living organism has not been studied. Nuclear medicine imaging is superior technology for the noninvasive analysis of the temporal distribution of drug candidates in living organisms. Gamma-ray emission imaging (GREI), which was developed by our laboratory as a novel molecular imaging modality, was adopted to visualize various γ-ray-emitting radionuclides that are not detected by conventional imaging techniques such as positron emission tomography and single-photon emission computed tomography. Therefore, we applied GREI to a biodistribution assay of Zn complexes. In the present study, ⁶⁵Zn was produced in the ^natCu(p,n) reaction in an azimuthal varying field cyclotron for the GREI experiment. The distribution was then noninvasively visualized using GREI after the intravenous administration of a ⁶⁵Zn-labeled di(1-oxy-2-pyridinethiolato)zinc [Zn(opt)₂], ZnCl₂, and di(l-histidinato)zinc. The GREI images were validated using conventional invasive assays. This novel study showed that GREI is a powerful tool for the biodistribution analysis of antidiabetic Zn complexes in a living organism. In addition, accumulation of ⁶⁵Zn in the cardiac blood pool was observed for [Zn(opt)₂], which exhibits potent antidiabetic activity. These results suggest that the slow elimination of Zn from the blood is correlated to the antidiabetic activity of [Zn(opt)₂].

Keywords: 65Zn-labeled Zn complex; Biodistribution; DM, Diabetes mellitus; DMSO, Dimethyl sulfoxide; GREI; GREI, Gamma-ray emission imaging; PET, Positron emission tomography; SPECT, Single-photon emission computed tomography; [Zn(His)2], Di(l-histidinato)zinc; [Zn(opt)2], Di(1-oxy-2-pyridinethiolato)zinc.