One-Step Automatic Radiosynthesis and Evaluation of [ 18 F]TM-30089 as GPR44 Radiotracer.

Autor: Peng, Jiangling, Tang, Wei, Rawson, Jeffrey, Miao, Lynn, Gonzalez, Nelson, Yin, Runkai, Chen, Jiaqi, Ji, Melinda, Li, Zhixuan, Gao, Anna, Wu, Andy Z., Shively, John E., Kandeel, Fouad, Li, Junfeng
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Zdroj: Pharmaceuticals (14248247); Oct2023, Vol. 16 Issue 10, p1480, 13p
Abstrakt: Recently, a G-protein coupled receptor 44 (GPR44) was discovered to play a significant role in the process of inflammation-related diseases, including cancer and diabetes. However, the precise role of GPR44 has yet to be fully elucidated. Currently, there is a strong and urgent need for the development of GPR44 radiotracers as a non-invasive methodology to explore the exact mechanism of GPR44 on inflammation-related diseases and monitor the progress of therapy. TM-30089 is a potent GPR44 antagonist that exhibits a high specificity and selectivity for GPR44. Its structure contains a fluorine nuclide, which could potentially be replaced with 18F. In the present study, we successfully took a highly effective synthesis strategy that pretreated the unprotected carboxylic acid group of the precursor and developed a feasible one-step automatic radiosynthesis strategy for [18F]TM-30089 with a high radiochemical purity and a good radiochemical yield. We further evaluated this radiotracer using mice models implanted with 1.1 B4 cell lines (GPR44-enriched cell lines) and human islets (high GPR44 expression), respectively. The results revealed the persistent and specific uptake of [18F]TM-30089 in GPR44 region, indicating that [18F]TM-30089 is a promising candidate for targeting GPR44. Further evaluation is ongoing. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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