Elucidation of renal tubular secretion mechanism of drugs and development of new renal functional methods in nuclear medicine

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07747
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52040:Radiological sciences-related
• Research Institution: Kanazawa University
• Principal Investigator: Kobayashi Masato 金沢大学, 保健学系, 准教授 (30444235)
• Co-Investigator(Kenkyū-buntansha): 川井 恵一 金沢大学, 保健学系, 教授 (30204663)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 核医学 / イメージング / 腎臓 / 薬物トランスポータ / CT造影剤

Outline of Final Research Achievements

Although accurate measurement of renal excretory function is clinically important, the renal tubular secretion mechanism and tubular epithelial cell accumulation have not been fully elucidated. In this study, we develop a nuclear medicine imaging method that can accurately and specifically measure the amount of proximal tubular secretion, and the mechanism of proximal tubular secretion of drugs whose side effects are a problem in clinical examinations. As a result, OAT3 expressed in the basolateral membrane on the tubular epithelial cell vascular side was involved in the renal cortex accumulation of [99mTc]DMSA. In addition, the non-ionic iodine contrast agent Iopamiron is taken up into renal tubular epithelial cells from the tubular lumen side via MATE1 and MATE2-K, and accumulates and stays there. It has been reducing the survival rate of renal cells.

Free Research Field

放射線科学

Academic Significance and Societal Importance of the Research Achievements

腎機能の正確かつ特異的に定量測定可能な核医学画像測定法の開発を目指して，臨床画像検査用腎シンチグラフィの一つである[99mTc]DMSAの腎皮質に対する集積機序に有機アニオントランスポーターOAT3が関与していることを解明した．また，臨床検査で腎臓での副作用が問題となっている非イオン性ヨード造影剤イオパミロンの近位尿細管分泌機序にH+/有機カチオンアンチポーターMATE1と2-Kが関わっており，基底膜側の薬物トランスポータの関与がなかったため尿細管上皮細胞に集積することを発見した.