PET Imaging of GPR44 by Antagonist [11C]MK-7246 in Pigs

Biomedicines

Olle Korsgren¹  Jonas Eriksson²  Sergio Estrada²  MohammadA. Amin²  Sofie Ye²  LukeR. Odell²  Olof Eriksson³  Pierre Cheung³  Emmi Puuvuori³  Bo Zhang³ 

[1] Department of Immunology, Genetics and Pathology, Uppsala University, 751 83 Uppsala, Sweden;Department of Medicinal Chemistry, Uppsala University, 751 83 Uppsala, Sweden;Science for Life Laboratory, Uppsala University, 751 83 Uppsala, Sweden;

关键词: pancreas imaging;    diabetes;    biomarker;    PET;    PTGDR2;   

DOI  :  10.3390/biomedicines9040434

来源: DOAJ

【 摘 要 】

A validated imaging marker for beta-cell mass would improve understanding of diabetes etiology and enable new strategies in therapy development. We previously identified the membrane-spanning protein GPR44 as highly expressed and specific to the beta cells of the pancreas. The selective GPR44 antagonist MK-7246 was radiolabeled with carbon-11 and the resulting positron-emission tomography (PET) tracer [¹¹C]MK-7246 was evaluated in a pig model and in vitro cell lines. The [¹¹C]MK-7246 compound demonstrated mainly hepatobiliary excretion with a clearly defined pancreas, no spillover from adjacent tissues, and pancreatic binding similar in magnitude to the previously evaluated GPR44 radioligand [¹¹C]AZ12204657. The binding could be blocked by preadministration of nonradioactive MK-7246, indicating a receptor-binding mechanism. [¹¹C]MK-7246 showed strong potential as a PET ligand candidate for visualization of beta-cell mass (BCM) and clinical translation of this methodology is ongoing.

【 授权许可】

Unknown