Synthesis of L-[5- C]Leucine and L-α-[5- C]Methylleucine via Pd -mediated C-Methylation and Microfluidic Hydrogenation: Potentiality of Leucine PET Probes for Tumor Imaging.

The efficient synthesis of L-[5- C]leucine and L-α-[5- C]methylleucine has been investigated using a continuous two-step sequence of rapid reactions consisting of Pd -mediated C-methylation and microfluidic hydrogenation. The synthesis of L-[5- C]leucine and L-α-[5- C]methylleucine was accomplished within 40 min with a decay-corrected radiochemical yield of 15-38 % based on [ C]CH I, radiochemical purity of 95-99 %, and chemical purity of 95-99 %. The Pd impurities in the injectable solution measured using inductively coupled plasma mass spectrometry met the international criteria for human use. Positron emission tomography scanning after an intravenous injection of L-[5- C]leucine or L-α-[5- C]methyl leucine in A431 tumor-bearing mice was performed. As a result, L-α-[5- C]methylleucine was found to be a potentially useful probe for visualizing the tumor. Tissue distribution analysis showed that the accumulation value of L-α-[5- C]methylleucine in tumor tissue was high [12±3% injected dose/g tissue (%ID/g)].