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Author Notes:

Corresponding author: Mark M. Goodman, Department of Radiology, Emory University, 1364 Clifton Road NE, Atlanta, GA 30322, Phone: (404) 727-9366, Fax: (404) 727-4366, mgoodma@emory.edu

J.M. currently at Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110

Subject:

Research Funding:

National Cancer Institute : NCI

We acknowledge the use of Shared Instrumentation provided by grants from the NIH and the NMP for the mass spectrometry data.

Synthesis, Radiolabeling and Biological Evaluation of (R)- and (S)-2-Amino-3-[18F]Fluoro-2-Methylpropanoic Acid (FAMP) and (R)- and (S)-3-[18F]Fluoro-2-Methyl-2-N-(Methylamino)propanoic Acid (NMeFAMP) as Potential PET Radioligands for Imaging Brain Tumors

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Journal Title:

Journal of Medicinal Chemistry

Volume:

Volume 53, Number 2

Publisher:

, Pages 876-886

Type of Work:

Article | Post-print: After Peer Review

Abstract:

The non-natural amino acids (R)- and (S)-2-amino-3-fluoro-2-methylpropanoic acid 5 and (R)- and (S)-3-fluoro-2-methyl-2-N-(methylamino)propanoic acid 8 were synthesized in shorter reaction sequences than in the original report starting from enantiomerically pure (S)- and (R)-α-methyl-serine, respectively. The reaction sequence provided the cyclic sulfamidate precursors for radiosynthesis of (R)- and (S)-[18F]5 and (R)- and (S)-[18F]8 in fewer steps than in the original report. (R)- and (S)-[18F]5 and(R)- and (S)-[18F]8 were synthesized by no-carrier-added nucleophilic [18F]fluorination in 52–66% decay-corrected-yields with radiochemical purity over 99%. The cell assays showed that all four compounds were substrates for amino acid transport and enter 9L rat gliosarcoma cells in vitro at least in part by system-A amino acid transport. The biodistribution studies demonstrated that in vivo tumor to normal brain ratios for all compounds were high with ratios of 20:1 to115:1 in rats with intracranial 9L tumors. The (R)- enantiomers of [18F]5 and [18F]8 demonstrated higher tumor uptake in vivo compared to the (S)- enantiomers.

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© 2009 American Chemical Society

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