Noninvasive evaluation of GLP-1 receptor in central nervous system

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K20931
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0904:Internal medicine of the bio-information integration and related fields
• Research Institution: Kyoto University
• Principal Investigator: Murakami Takaaki 京都大学, 医学研究科, 助教 (50904017)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: 糖尿病 / GLP-1受容体 / イメージング

Outline of Final Research Achievements

Mice were injected intravenously with 111In-Ex4 probe in the tail and SPECT/CT imaging was performed including the head. Limited significant accumulation was observed in the hypothalamus/pituitary region, which could be visualized at the same time as the pancreas. No significant accumulation was observed in other intracranial regions. The significant accumulation disappeared after pre-treatment with Ex(9-39). Next, the pituitary gland, hypothalamus, cerebrum, and pancreas were collected after administration of the probe, and RI accumulation values were measured with a γ counter. Stable accumulation was observed in the pituitary gland, but not in the hypothalamus or cerebrum. The GLP1-R mRNA expression level in the pituitary gland was significantly correlated with the RI accumulation level, indicating that the pituitary gland was responsible for the accumulation observed on 111In-Ex4 SPECT images.

Free Research Field

糖尿病

Academic Significance and Societal Importance of the Research Achievements

中枢神経領域での111In-Ex4プローブ集積像は膵臓と同時に描出できたことから、GLP-1R標的膵・中枢神経同時イメージングが可能であった。また、画像上の解剖学的位置情報や、Biodistribution studyの結果から、同有意集積領域は下垂体へのプローブ集積シグナルであることが明らかになった。また、SPECT画像上の同領域のRI集積値とGLP-1R mRNA発現量は有意な相関関係を示すことから、111In-Ex4 SPECT/CTにより、膵β細胞量同様、下垂体のGLP-1R発現に関する量的情報を非侵襲的に得られる可能性がある。