2022 Fiscal Year Final Research Report
Development of nuclear medicine imaging technology in the diagnosis of primary aldosteronism
Project/Area Number |
20K08061
|
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 | Kyoto Pharmaceutical University |
Principal Investigator |
|
Project Period (FY) |
2020-04-01 – 2023-03-31
|
Keywords | アルドステロン産生腺腫 / CYP11B2 / イメージングプローブ / PET / SPECT |
Outline of Final Research Achievements |
To develop a new radiolabeled probe for PET (Positron Emission Tomography) and SPECT (Single Photon Emission Computed Tomography) that can specifically detect aldosterone synthesis-related enzyme CYP11B2, we have developed a new probe based on the structural information of previously reported imaging probes. The synthesized compounds were evaluated for their inhibitory activity against CYP11B1 and CYP11B2, and a compound with high specificity for CYP11B2 was successfully obtained. From the evaluation of the distribution kinetics of the candidate compounds in mice, we succeeded in obtaining compounds that showed high accumulation in the adrenal gland. Finally, we performed an ARG (autoradiography) on a candidate compounds using tissue sections of an aldosterone-producing adenoma provided by a patient, and found a compound that strongly accumulated at sites where CYP11B2 was positive by immunohistochemistry.
|
Free Research Field |
放射薬学
|
Academic Significance and Societal Importance of the Research Achievements |
原発性アルドステロン症(PA)は、高血圧患者の約5-6%を占め、代表的な二次性高血圧の一つである。PAは主にアルドステロン産生腺腫(APA)と特発性アルドステロン症に大別される。APAの局在診断には副腎静脈サンプリングが必須であるが、技術的に成功率が高い施設が限られており、また、患者さんへの負担も大きく、代替の簡便な局在診断法の開発が望まれている。新規分子イメージングプローブに基づく新たなAPAの検査法を開発できれば、日本発・世界初の普及可能な検査として、多くの患者を治療に結びつけることが可能となる。
|