Preclinical evaluation of 5-([11C]-methyloxy)-L-tryptophan as a potential PET molecular imaging probe.

OBJECTIVE: The new tumor probe 5-([C]-methyloxy)-L-tryptophan ([C]-L-CMTP) had been found to show high uptake in tumor tissue in our previous report; however, the pharmacokinetic properties of [C]-L-CMTP have not been characterized. In this present study, we evaluated the potential of [C]-L-CMTP as a PET probe for tumor imaging.

METHODS: The biodistribution of [C]-L-CMTP was determined in healthy mice and the incorporation of [C]-L-CMTP into proteins was investigated. In-vitro competitive inhibition experiments were conducted with Hepa1-6 hepatoma cell lines. [C]-L-CMTP PET imaging was performed on S180 tumor-bearing mice and lung tumor-bearing mice.

RESULTS: Biodistribution studies showed high uptake of [C]-L-CMTP in the liver, kidney, and pancreas, but low uptake in brain. The transport assay studies in Hepa1-6 cells suggested that [C]-L-CMTP was mainly transported by the amino acid transport system B and LAT1. [C]-L-CMTP was not incorporated into proteins in vitro. PET imaging showed that [C]-L-CMTP had high uptake in S180 fibrosarcoma tumor and lung tumor.

CONCLUSION: [C]-L-CMTP was not incorporated into proteins and was mainly transported by the amino acid transport system B and LAT1, PET imaging showed that [C]-L-CMTP had high uptake in tumor models; it seemed to be a promising PET probe for tumor by LAT1 transport. Video abstract: https://links.lww.com/NMC/A70.