Synthesis and biological evaluation of anti-1-amino-2-[18F]fluoro-cyclobutyl-1-carboxylic acid (anti-2-[18F]FACBC) in rat 9L gliosarcoma

A new [18F] labeled amino acid anti-1-amino-2-[18F]fluoro-cyclobutyl-1-carboxylic acid 9 (anti-2-[18F]FACBC) was synthesized in 30% decay-corrected yield with high radiochemical purity over 99%. The cyclic sulfamidate precursor was very stable and highly reactive towards nucleophilic radiofluorination. Cell uptake assays with rat 9L gliosarcoma cells showed that [18F]9 was transported into tumor cells via multiple amino acid transport systems, including L and A systems. Biodistribution study in rats with intracranial 9L gliosarcoma tumors demonstrated that [18F]9 had a rapid and prolonged accumulation in tumors with 26:1 tumor to brain ratio at 120 min post-injection. In this model, [18F]9 is a potential PET tracer for brain tumor imaging.

Graphical abstractanti-2-FACBC 9, the constitutional isomer of anti-FACBC, has been synthesized and [18F] radiofluorinated in 30% decay-corrected yield. Biological evaluation using rat 9L gliosarcoma model showed that this tracer entered tumor cells via multiple amino acid transport systems including system L and system A in vitro with high tumor to brain ratio of 26:1 at 120 min post-injection in vivo.Figure optionsDownload full-size imageDownload as PowerPoint slide