Synthesis of 5-[18F]Fluoro-α-methyl Tryptophan: New Trp Based PET Agents

Indoleamine 2,3-dioxygenase (IDO1) plays a special role in the biology of various cancer types, because it breaks down the essential amino acid tryptophan for immune cell activation. Upregulation of IDO1 significantly correlates with the number of various T cell types in tumor tissues in melanoma and other cancers, suggesting that IDO expression is linked with effective and ineffective ('exhausted') immune response in cancer. Based on the reported IDO inhibitors (alpha-Methylated and indole-N-methylated tryptophan (Trp)), here we report the synthesis of potential IDO1 imaging agents through direct introduction of F-18 into the tryptophan aromatic ring. Overall, the resulting PET agents could be obtained in high radiochemical purity (>97%) with labeling yield ranges from 4.2-14.9% decay corrected yield. Using Trp as the model compound, our results also demonstrate that F-18 could be directly introduced to the Trp backbone at the 4, 5, 6, and 7 position. Moreover, our initial imaging study suggests that 5-[F-18]F-L-alpha-methyl tryptophan (5-[F-18]F-AMT) holds great potential for cancer imaging. The success of this approach will provide researchers easy access to a library of Trp/Trp-derivative based PET agents for biomedical research, including potential IDO1 targeted imaging.