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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, 65 Zn- and 131 I-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 65 Zn and [ 131 I]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 65 Zn for [Zn(Cq) 2 ] than ZnCl 2 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.

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