Development of a halogenated derivative of aromatic amino acids for the targeted alpha-radionuclide therapy with high tumor specificity and low renal background.

2016 Fiscal Year Final Research Report

• Project/Area Number: 16H06942
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: General pharmacology
• Research Institution: Osaka University
• Principal Investigator: Wei Ling 大阪大学, 医学系研究科, 特任助教(常勤) (80783638)
• Project Period (FY): 2016-08-26 – 2017-03-31
• Keywords: 癌 / α線内用療法 / トランスポーター / 構造活性相関 / ハロゲン化芳香族アミノ酸誘導体

Outline of Final Research Achievements

Targeted α-radionuclide therapy (TAT) is an upcoming powerful method for cancer treatment. One of halogens, 211At, has been attracting increasing attention as a novel α-particle emitting-radionuclide. A halogenated derivative of aromatic amino acid, FAMT (L-[3-18F]-α-methyltyrosine), developed as a PET tracer for tumor imaging exhibits an excellent cancer specificity. Therefore, substitution of 18F of FAMT with 211At would be a promising approach to develop a novel 211At-delivery agent for TAT. However, FAMT shows a significant background accumulation in kidney, due to the interaction with organic ion transporters in the renal proximal tubule. In this study, we used FAMT-related aromatic amino acid derivatives to reveal the molecular structures involved in the recognition by the renal organic ion transporters. This study gives significant implications for the development of a novel compound for TAT with high tumor specificity and low renal background accumulation.

Free Research Field

薬理学