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

• Main Authors: Jiangling Peng (Author), Wei Tang (Author), Jeffrey Rawson (Author), Lynn Miao (Author), Nelson Gonzalez (Author), Runkai Yin (Author), Jiaqi Chen (Author), Melinda Ji (Author), Zhixuan Li (Author), Anna Gao (Author), Andy Z. Wu (Author), John E. Shively (Author), Fouad Kandeel (Author), Junfeng Li (Author)
• Format: Book
• Published: MDPI AG, 2023-10-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/ph16101480; 1424-8247
• Keywords: G protein-coupled receptor 44 (GPR44); ¹⁸F-labeling; chemoattractant receptor-homologous molecule expressed on T-helper type 2 cells (CRTH2); prostaglandin D₂ receptor 2 (DP2); prostaglandin D₂ (PGD₂); inflammation; Medicine; R; Pharmacy and materia medica; RS1-441
• Source: Pharmaceuticals, Vol 16, Iss 10, p 1480 (2023)

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.