前立腺がんのPET診断薬の創出を目的とした逆アミド型PSMAリガンドの創薬研究

反向酰胺 PSMA 配体的药物发现研究，旨在创建前列腺癌 PET 诊断药物

• 批准号: 21K15227
• 负责人: 中嶋 龍
• 金额: $ 2.91万
• 依托单位: Hiroshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Early-Career Scientists
• 财政年份: 2021
• 资助国家: 日本
• 起止时间: 2021-04-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-21K15227/
• 关键词: PSMA; 前立腺がん; PET; 構造活性相関; 創薬研究

前立腺がんは日本国内の男性がん別罹患者数が第一位であり、高齢化とともに罹患率が上昇するため、高齢化社会の日本において最も注意しなければならないがんの一つと言える。既存の前立腺がんの診断方法（PSA血液検査等）は精度が低い傾向にあり、精度の高い診断方法の確立が急務である。近年、PSMAと呼ばれる膜抗原が通常の前立腺細胞と比較し、前立腺がん細胞に100-1000倍過剰に発現していることが判明したことから、このPSMAに結合するPSMAリガンドを放射性同位体で標識したPET診断が注目を集めている。PSMAリガンドを用いたPET診断の臨床試験結果から、前立腺がん陽性的中率は既存の診断法を比較して非常に高いだけでなく、前立腺がんから転移したがんの発見も可能であることが報告されている。研究代表者は、2－アミノアジピン酸というアミノ酸を出発原料とする新規PSMAリガンドが従来のリシン（アミノ酸）由来のPSMAリガンドと比較し、より高い結合能を有する傾向にあることを報告している。このようにPSMAリガンドを形成しているアミノ酸の種類を変えることで、PSMAリガンドの結合能を向上させることが可能なことから、本研究では様々なアミノ酸を有する新規PSMAリガンドを合成し、PSMAリガンドに最適な構造を見出すことを目的としている。最適な構造が見出すことができれば、前立腺がんの所在を早期発見するためのPET診断薬として利用可能なだけでなく、前立腺がん細胞に選択的に作用する化学療法薬としてのPSMAリガンドの創出が可能になると考えられる。現在、新たに設計した2－アミノアジピン酸由来の逆アミド型PSMAリガンドの骨格構築に成功したので、種々の誘導体合成を行い、その最適構造を探索している。

The number of male patients in Japan is the highest, the attack rate is high, and the society is high. Pay most attention to the disease. The existing pre-standing gland termination methods (PSA blood test, etc.) are accurate and accurate, while the high-precision and high-precision methods ensure that urgent tasks are required. In recent years, the membrane antigen of PSMA has been detected in the prestanding gland, the cell ratio of the prestanding gland is 100-1000 times higher than that of the prostatic gland. In recent years, the membrane antigen of the prestanding gland is 100-1000 times higher than that of the anterior adenoid. in recent years, the membrane antigen of the prestanding gland is 100-1000 times higher than that of the anterior adenoid. in recent years, the membrane antigen of the prestanding gland is more sensitive than that of the anterior adenoid. in recent years, the membrane antigen of the prestanding gland is 100-1000 times higher than that of the anterior adenoid. in recent years, the membrane antigen of the prestanding gland is 100-1000 times higher than that of the anterior adenoid. in recent years, the membrane antigen of the prestanding gland is 100-1000 times higher than that of the anterior adenoid. in The results of the bed test and the median rate of sex in the anterior standing gland of the PSMA were significantly higher than those in the anterior standing gland. the results showed that the incidence of sex in the anterior standing gland was significantly higher than that in the anterior standing gland. the results showed that the results showed that the incidence of sex in the anterior standing gland was significantly higher than that in the anterior standing gland. the results showed that there was a significant difference between the two groups. The representative of the research, the representative of the research, said that the raw material, the new PSMA, the raw material, the raw material, the raw material, In this study, there are some new problems in the synthesis of new PSMA compounds, and the results show that there are significant differences between the two groups in this study. in this study, the results show that there are significant differences between the two groups in this study. in this study, the results show that there are significant differences between the two groups in this study. in this study, the results show that there are significant differences between the two groups in this study. in this study, the results show that there are significant differences between the two groups in this study. in this study, the results show that there are significant differences between the two groups. In this study, the results show that there are significant differences in the synthesis of new PSMA systems, and the most effective methods in this study. In the early stage, we can see that the PET is located in the early stage of the selection of the cells of the anterior adenoid. in the early stage, we can make use of the chemical methods selected by the selection of the cells of the anterior standing glands. in the early stage, we can use the chemical methods to determine the effects of the cells of the anterior standing glands. in the early stage, we can use the chemical method to find out the possibility. At present, the new equipment design device 2-the cause of the problem is that the PSMAsystem has been successfully tested, the synthesis of various materials has been carried out, and the most advanced exploration equipment has been built.