Abstract
1904
Objectives (S)- and (R)-3-[18F]fluoro-2-methyl-2-N-(methylamino)propanoic acid (NMeFAMP) were synthesized and evaluated as PET brain tumor imaging agents in a 9L rat gliosarcoma model.
Methods The cyclic sulfamidate labeling precursors were prepared from (R)-and (S)-α-methyl-serine. Treatment with di-t-butyl dicarbonate followed by N,N-dimethylformamide di-t-butyl acetal gave (R)- and (S)-N-Boc α-methyl-serine t-butyl ester. Treatment with SOCl2, NaIO4, removal of the N-Boc and N-methylation gave the labeling precursors. (S)-and (R)-[18F]NMeFAMP were obtained by treatment with K[18F]F/K222, 4N HCl and chromatographic purification. Amino acid transport inhibition studies were performed with 9L rat gliosarcoma cells with 30 min incubations at 37 oC under control conditions, with 10 mM of BCH, system L inhibitor, or with 10 mM NMeAIB, system A inhibitor. Biodistribution studies were carried out in 9L tumor-bearing Fisher rats. The uptake (%ID/g) in tumor and normal tissue was measured at 15, 30, 60, 120 min post injection.
Results (S)- and (R)-[18F]NMeFAMP were obtained in 68% and 64% DCY (n=7), respectively, with radiochemical purity over 99%. The uptake of (S)- and (R)-[18F]NMeFAMP was inhibited 29-54% by BCH and 79-92% by MeAIB. The tumor to brain uptake ratios of (S)- and (R)-[18F]NMeFMAP were 18-138:1 with relatively low uptake in bone.
Conclusions (S)-and (R)-[18F]NMeFAMP were prepared in high DCY. Cell assay results suggested that (S)-and (R)-NMeFAMP entered tumor cells primarily via system A transport. Biodistribution studies with both enantiomers showed a high and prolonged accumulation of radioactivity in tumors with excellent tumor to brain ratios. These results support the candidacy of (S)-and (R)-[18F]NMeFAMP as PET brain tumor imaging agents.
Research Support Research supported by NIH R21 CA098891, and Nihon Medi-Physics Co., Ltd.
- © 2009 by Society of Nuclear Medicine