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

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 F-18. 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 [F-18]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 [F-18]TM-30089 in GPR44 region, indicating that [F-18]TM-30089 is a promising candidate for targeting GPR44. Further evaluation is ongoing

Automated summary

GPR44 has been found to play a significant role in inflammation-related diseases, but its precise mechanism is still unclear. This study successfully developed [F-18]TM-30089 as a radiotracer for GPR44 and demonstrated its promising targeting ability. This may contribute to the understanding of GPR44's mechanism and monitoring of therapeutic progress.