Synthesis, Radiolabeling, and Biological Evaluation of the Cis Stereoisomers of 1-amino-3-(fluoro- ¹⁸ F)-4-fluorocyclopentane-1-carboxylic acid as PET Imaging Agents

The non-natural cyclic amino acids (1S,3R,4S)-1-amino-3-fluoro-4-(fluoro-^<i>18F</i>)cyclopentane-1-carboxylic acid ([^<i><b>18F</i>]9</b>) and (1S,3S,4R)-1-amino-3-fluoro-4-(fluoro-^<i>18F</i>)cyclopentane-1-carboxylic acid ([^<i><b>18F</i>]28</b>) have been prepared in 10% and 1.7% decay corrected radiochemical yield, respectively, and in greater than 99% radiochemical purity. Cell assays in rat 9L glio-sarcoma, human U87 ∆EGFR glioblastoma, and human DU145 androgen-independent prostate carcinoma tumor cells indi-cated that both compounds are substrates for amino acid transport primarily by system L, with some transport taking place via system ASC. In rats with 9L gliosarcoma, [^<i>18F]9</i> and [^<b><i>18F]28</i></b> provided high tumor to normal brain tissue ratios, with maximal ratios of 3.5 and 4.1, respectively. Biodistribution studies in healthy rats confirmed that both compounds are BBB permeable, and that bladder accumulation is low until at least 5 minutes post injection.