Characterization of the two enantiomers of anti-18F-FACPC as PET tumor agents

1516 Objectives (R,S) Anti-1-amino-2-[18F]fluorocyclopentyl-1-carboxylic acid (18F-FACPC) has been reported as a potent tumor-detecting agent for positron emission tomography (PET). Our in vitro and in vivo 9L tumor studies indicated that 18F-FACPC was transported via system L and showed high tumor uptake.1 The goal of this study was to evaluate, in vitro, the transport properties of that tracer isolated enantiomers and their suitability for tumor detection. Methods 16 and 17 were prepared from their precursors 14 and 15, by no-carrier-added nucleophilic substitution. A comparison of uptake studies of 18F-FACPC and its enantiomers was performed in 9L gliosarcoma cells. The biological behavior of 16 and 17 was further evaluated in vitro, using human glioma (U87MG) and different types of human breast cancer, MDA mb 231, mb 435, and mb 468. Results 16 and 17 were obtained in an average decay-corrected yield of 25% (n=5) and enantiomeric purity of > 90%. The absolute configurations of 16 and 17 have not been confirmed yet. They will be referred to, as peaks 1 and 2, corresponding to their order of appearance on a chiral column. The in vitro assays performed using 9L gliosarcoma cells in the presence of inhibitors of amino acid transport, BCH, MeAIB, and ACS demonstrated that 16 and 17 are substrates for system L with peak 1 showing higher accumulation in tumor (12%) than peak 2 (7%). The in vitro assays performed using U87MG, MDA mb231, mb 435, and mb 468 cancer cells showed that, in the absence of inhibitors, peak 1 displayed tumor uptakes of 28%, 9%, 4%, and 7% comparing to peak 2, 17%, 6.4%, 2.6%, and 5.3%, respectively. Moreover, these results confirm the transport of 16 and 17 with system L. Conclusions 16 and 17 are useful amino acids for the diagnosis of cancer using PET. Peak 1 shows significantly higher cell uptake and may be a more powerful tool as a tumor-detecting agent for PET, especially for the imaging of a brain cancer. Research Support 1. N. Jarkas, R. V. Voll, V. M. Camp, L. Williams, E. Malveaux, and M. M. Goodman. J. Labelled Cpd. Radiopharm., 2009; Suppl. 1; S19