Abstract
1324
Objectives: S/R-2-amino-2-methyl-3-[18F]fluoro-propanoic acids (S/R-[18F]FAMP) were synthesized and evaluated as PET brain tumor imaging agents in 9L rat gliosarcoma model.
Methods: S/R-FAMP precursors for labeling were prepared in 4 steps from S/R-α-Me-Ser. Protected N-Boc amino acid t-Bu esters were treated with SOCl2 then NaIO4 to give S/R-FAMP cyclic sulfamidates as precursors. S/R-[18F]FAMP were obtained by radiofluorination with [18F]KF/K222 followed by acid hydrolysis then chromatographic purification. In vitro studies were performed in 9L cells in HBSS incubated for 30 min at 37\#9675;C with/without inhibitors, BCH and MeAIB, L-(LAT) and A-(AAT) type, respectively. In vivo studies were carried out in tumor-bearing Fisher rats. The radioactivity in tumors and in normal tissues (n=5/time point) was calculated at 30, 60, 120 min p.i. and normalized as % injected dose/gram tissue (%ID/g).
Results: [18F]FAMP was obtained in 48% (S-FAMP) and 56% (R-FAMP) radiolabeling yields with over 99% radiochemical purity by radiometric TLC. The cell uptake was 13% (S-FAMP) and 5% (R-FAMP) initial dose/0.5 million cells without inhibitors. Inhibition of S-[18F]FMAP and R-[18F]FMAP was 67 and 75%, respectively by BCH and 58 and 31%, respectively by MeAIB. S/R-[18F]FMAP uptake ratios of tumor to brain were 24-40:1. Low uptake was found in blood, muscle and bone.
Conclusions: Radiosyntheses of S/R-[18F]FAMP were achieved with high yield and radiochemical purity. Cell assay results suggested that S/R-FAMP entered tumor cells in high level in vitro via both AAT and LAT with R-FAMP showing LAT selectivity. In vivo studies showed rapid and prolonged uptake of activity in tumors with good tumor to brain ratios. These results support the candidacy of S/R-[18F]FAMP as PET brain tumor imaging agents.
Research Support: NIH and Nihon Medi-Physics.
- Society of Nuclear Medicine, Inc.