Investigation of Biodistribution and Speciation Changes of Orally Administered Dual Radiolabeled Complex, Bis(5-chloro-7-[<sup>131</sup>I]iodo-8-quinolinolato)[<sup>65</sup>Zn]zinc

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  • Munekane Masayuki
    Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Japan Society for the Promotion of Science Next-Generation Imaging Team, RIKEN Center for Life Science Technologies
  • Ueda Masashi
    Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
  • Motomura Shinji
    Next-Generation Imaging Team, RIKEN Center for Life Science Technologies
  • Kamino Shinichiro
    Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Next-Generation Imaging Team, RIKEN Center for Life Science Technologies
  • Haba Hiromitsu
    RIKEN Nishina Center for Accelerator-Based Science, RIKEN
  • Yoshikawa Yutaka
    Department of Health, Sports, and Nutrition Faculty of Health and Welfare, Kobe Women’s University
  • Yasui Hiroyuki
    Department of Analytical and Bioinorganic Chemistry, Division of Analytical and Physical Chemistry, Kyoto Pharmaceutical University
  • Enomoto Shuichi
    Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Next-Generation Imaging Team, RIKEN Center for Life Science Technologies

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  • Investigation of Biodistribution and Speciation Changes of Orally Administered Dual Radiolabeled Complex, Bis(5-chloro-7-[¹³¹I]iodo-8-quinolinolato)[⁶⁵Zn]zinc

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Abstract

<p>Many zinc (Zn) complexes have been developed as promising oral antidiabetic agents. In vitro assays using adipocytes have demonstrated that the coordination structures of Zn complexes affect the uptake of Zn into cells and have insulinomimetic activities, for which moderate stability of Zn complexes is vital. The complexation of Zn plays a major role improving its bioavailability. However, investigation of the speciation changes of Zn complexes after oral administration is lacking. A dual radiolabeling approach was applied in order to investigate the speciation of bis(5-chloro-7-iodo-8-quinolinolato)zinc complex [Zn(Cq)2], which exhibits the antidiabetic activity in diabetic mice. In the present study, 65Zn- and 131I-labeled [Zn(Cq)2] were synthesized, and their biodistribution were analyzed after an oral administration using both invasive conventional assays and noninvasive gamma-ray emission imaging (GREI), a novel nuclear medicine imaging modality that enables analysis of multiple radionuclides simultaneously. The GREI experiments visualized the behavior of 65Zn and [131I]Cq from the stomach to large intestine and through the small intestine; most of the administered Zn was transported together with clioquinol (5-chloro-7-iodo-8-quinolinol) (Cq). Higher accumulation of 65Zn for [Zn(Cq)2] than ZnCl2 suggests that the Zn associated with Cq was highly absorbed by the intestinal tract. In particular, the molar ratio of administered iodine to Zn decreased during the distribution processes, indicating the dissociation of most [Zn(Cq)2] complexes. In conclusion, the present study successfully evaluated the speciation changes of orally administered [Zn(Cq)2] using the dual radiolabeling method.</p>

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