Document Detail


Synthesis, radiolabeling, and biological evaluation of (R)- and (S)-2-amino-3-[(18)F]fluoro-2-methylpropanoic acid (FAMP) and (R)- and (S)-3-[(18)F]fluoro-2-methyl-2-N-(methylamino)propanoic acid (NMeFAMP) as potential PET radioligands for imaging brain tumors.
MedLine Citation:
PMID:  20028004     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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)-alpha-methyl-serine, respectively. The reaction sequence provided the cyclic sulfamidate precursors for radiosynthesis of (R)- and (S)-[(18)F]5 and (R)- and (S)-[(18)F]8 in fewer steps than in the original report. (R)- and (S)-[(18)F]5 and(R)- and (S)-[(18)F]8 were synthesized by no-carrier-added nucleophilic [(18)F]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 [(18)F]5 and [(18)F]8 demonstrated higher tumor uptake in vivo compared to the (S)-enantiomers.
Authors:
Weiping Yu; Jonathan McConathy; Larry Williams; Vernon M Camp; Eugene J Malveaux; Zhaobin Zhang; Jeffrey J Olson; Mark M Goodman
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  53     ISSN:  1520-4804     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2010-01-21     Completed Date:  2010-03-02     Revised Date:  2014-09-21    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  876-86     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Amino Acids / pharmacokinetics
Aminoisobutyric Acids / chemical synthesis,  diagnostic use*,  pharmacokinetics
Animals
Biological Transport
Brain Neoplasms / diagnosis*
Cell Line, Tumor
Isotope Labeling / methods
Positron-Emission Tomography / methods*
Radiopharmaceuticals / chemical synthesis,  diagnostic use,  pharmacokinetics
Rats
Tissue Distribution
Grant Support
ID/Acronym/Agency:
R21 CA098891/CA/NCI NIH HHS; R21 CA098891-02/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/2-amino-3-fluoro-2-methylpropanoic acid; 0/Amino Acids; 0/Aminoisobutyric Acids; 0/Radiopharmaceuticals
Comments/Corrections

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