development of a novel imaging probe for alteration of mitochondria function based on cancer therapy

2015 Fiscal Year Final Research Report

• Project/Area Number: 25293262
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Magata Yasuhiro 浜松医科大学, 光尖端医学教育研究センター, 教授 (20209399)
• Co-Investigator(Kenkyū-buntansha): SAKAHARA HARUMI 浜松医科大学, 医学部, 教授 (10187031) ; SUZUKI CHIE 浜松医科大学, 光尖端医学教育研究センター, 助教 (20637285) ; OGAWA MIKAKO 北海道大学, 薬学研究院, 教授 (20344351)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 放射性医薬品 / がん / PET / SPECT / ミトコンドリア / 膜電位 / 多剤耐性輸送タンパク

Outline of Final Research Achievements

For the purpose prediction of therapeutic effect and early judgment of the therapy, we developed a novel imaging probe to estimate mitochondria function which relates "apoptosis", or "oxygen". We have already obtained the radioiodinated labeled compound I-125-DPP which accumulates to cells depending on their mitochondrial membrane potential. Unfortunately, this compound was excreted from the cells by P-glycoprotein (P-gp) just after uptake in the cells. In order to improve this problem, we designed and synthesized a new drug I-125-DESP including a styilbene group which is an inhibitor against P-gp. I-125-DESP was uptake 6.7 times higher into cancer cells compared with I-125-DPP. Moreover, almost I-125-DESP was not excreted from the cancer cells. These results indicate POC of the drug design of this compound. Then, we performed in vivo imaging studies with an animal SPECT machine. Unfortunately, high uptake of radioactivity in the liver was observed and tumor could not visualized.

Free Research Field

分子イメージング・病態機能分析学