Characteristic Evaluation of a C-Labeled Leucine Analog, l-α-[5-C]methylleucine, as a Tracer for Brain Tumor Imaging by Positron Emission Tomography.

Amino acid transporters are upregulated in many cancer cells, and system L amino acid transporters (LAT1-4), in particular, LAT1, which preferentially transports large, neutral, and branched side-chain amino acids, are considered a primary target for cancer positron emission tomography (PET) tracer development. Recently, we developed a C-labeled leucine analog, l-α-[5-C]methylleucine ([5-C]MeLeu), via a continuous two-step reaction of Pd-mediated C-methylation and microfluidic hydrogenation. In this study, we evaluated the characteristics of [5-C]MeLeu and also compared the sensitivity to brain tumors and inflammation with l-[C]methionine ([C]Met) to determine its potential for brain tumor imaging.

Synthesis and Preclinical Evaluation of F-Labeled Ketoprofen Methyl Esters for Cyclooxygenase-1 Imaging in Neuroinflammation.

Cyclooxygenase (COX) is a rate-limiting enzyme in the synthesis of proinflammatory prostanoids from arachidonic acid. In vivo imaging of COX by PET is a potentially powerful tool for assessing the inflammatory response to injury, infection, and disease. We previously reported on a promising PET probe for COX imaging, C-labeled ketoprofen methyl ester, which can detect COX-1 activation in models of neuroinflammation and neurodegenerative disorders.

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.