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[摘要]：The [F-18]fluorocyclobutyl group has the potential to be a metabolically stable prosthetic group for PET tracers. The synthesis of the radiolabeling precursor cis-cyclobutane-1,3-diyl bis(toluene-4-sulfonate) 8 was obtained from epibromohydrin in 7 steps (2% overall yield). The radiolabeling of this precursor 8 and its conjugation to L-tyrosine as a model system was successfully achieved to give the new non-natural amino acid 3-[F-18]fluorocyclobutyl-L-tyrosine (L-3-[F-18]FCBT) [F-18] 17 in 8% decay-corrected yield from the non-carrier-added [F-18] fluoride. L-3-[F-18] FCBT was investigated in vitro in different cancer cell lines to determine the uptake and stability. The tracer [F-18] 17 showed a time dependent uptake into different tumor cell lines (A549, NCI-H460, DU145) with the best uptake of 5.8% injected dose per 5 x 10(5) cells after 30 min in human lung carcinoma cells A549. The stability of L-3-[F-18] FCBT in human and rat plasma and the stability of the non-radioactive L-3-FCBT in rat hepatocytes were both found to be excellent. These results show that the non-natural amino acid L-3-[F-18] FCBT is a promising metabolically stable radiotracer for positron emission tomography. (C) 2012 Elsevier Ltd. All rights reserved. |
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