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S- and R-[¹⁸F]FAMP: PET brain tumor imaging agents

¹ Radiology; ² Neurosurgery, Emory University, Atlanta, Georgia

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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--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.

This Article Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Yu, W. Articles by Goodman, M. PubMed Articles by Yu, W. Articles by Goodman, M.