| 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 |
Related Documents
:
|
2868724 - Acute and short-term effects of lithium on glutamate metabolism in rat brain. 2330824 - Suppressant effects of dexamethasone on the availability of plasma l-tryptophan and tyr... 2428974 - Neurochemical characterization of the actions of 5-amino-2,4- dihydroxy-alpha-methylphe... 2874944 - Presence of corticotropin-like and opiate-like hormones in rat and bovine placental tis... 2935744 - Functional and neurochemical cortical cholinergic impairment following neurotoxic lesio... 837524 - A precise semi-automated uricase method for determining uric acid in serum or urine. |
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: 2011-07-20 |
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 |
Affiliation:
|
Department of Radiology, School of Medicine, Emory University, 1364 Clifton Road NE, Atlanta, Georgia 30322, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| 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 CA098891-02/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 | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: First-Principles Study of High-Pressure Behavior of Solid beta-HMX.
Next Document: A Topological Study of the Decomposition of 6,7,8-Trioxabicyclo[3.2.2]nonane Induced by Fe(II): Mode...