Document Detail

Synthesis of syn- and anti-1-amino-3-[18F]fluoromethyl-cyclobutane-1-carboxylic acid (FMACBC), potential PET ligands for tumor detection.
MedLine Citation:
PMID:  12014963     Owner:  NLM     Status:  MEDLINE    
syn- and anti-1-amino-3-[18F]fluoromethyl-cyclobutane-1-carboxylic acid (FMACBC, 16 and 17), analogues of anti-1-amino-3-[18F]fluorocyclobutyl-1-carboxylic acid (FACBC), were prepared to evaluate the contributions of C-3 substitution and configuration on the uptake of these radiolabeled amino acids in a rodent model of brain tumors. Radiofluorinated targets [18F]16 and [18F]17 were prepared by no-carrier-added radiofluorination from their corresponding methanesulfonyl esters 12 and 13, respectively, with decay-corrected radiochemical yields of 30% for [18F]16 and 20% for [18F]17. In amino acid transport assays performed in vitro using 9L gliosarcoma cells, both [18F]16 and [18F]17 were substrates for L type amino acid transport, while [18F]17 but not [18F]16 was a substrate for A type transport. Biodistribution studies in normal Fischer rats with [18F]16 and [18F]17 showed high uptake of radioactivity (>2.0% dose/g) in the pancreas while other tissues studied, including liver, heart, lung, kidney, blood, muscle, and testis, showed relatively low uptake of radioactivity (<1.0% dose/g). In rats implanted intracranially with 9L gliosarcoma cells, the retention of radioactivity in tumor tissue was high at 5, 60, and 120 min after intravenous injection of [18F]16 and [18F]17 while the uptake of radioactivity in brain tissue contralateral to the tumor remained low (<0.3% dose/g). Ratios of tumor uptake to normal brain uptake for [18F]16 were 7.5:1, 7:1, and 5:1 at 5, 60, and 120 min, respectively, while for [18F]17 the ratios were 7.5:1, 9:1, and 9:1 at the same time points. This work demonstrates that like anti-[18F]FACBC, [18F]16 and [18F]17 are excellent candidates for imaging brain tumors.
Laurent Martarello; Jonathan McConathy; Vernon M Camp; Eugene J Malveaux; Nicholas E Simpson; Chiab P Simpson; Jeffrey J Olson; Geoffrey D Bowers; Mark M Goodman
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  45     ISSN:  0022-2623     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2002 May 
Date Detail:
Created Date:  2002-05-16     Completed Date:  2002-06-07     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2250-9     Citation Subset:  IM    
Emory Center for Positron Emission Tomography, Department of Radiology, Emory University, 1364 Clifton Road, Northeast, Atlanta, Georgia 30322, USA.
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MeSH Terms
Amino Acid Transport System A / antagonists & inhibitors,  metabolism
Amino Acid Transport System L / antagonists & inhibitors,  metabolism
Amino Acids / chemical synthesis*,  chemistry,  pharmacokinetics
Brain / metabolism
Brain Neoplasms / metabolism
Carboxylic Acids / chemical synthesis*,  chemistry,  pharmacokinetics
Crystallography, X-Ray
Cyclobutanes / chemical synthesis*,  chemistry,  pharmacokinetics
Fluorine Radioisotopes
Gliosarcoma / metabolism
Isotope Labeling
Neoplasm Transplantation
Propionic Acids / chemical synthesis*,  chemistry,  pharmacokinetics
Radiopharmaceuticals / chemical synthesis*,  chemistry,  pharmacokinetics
Rats, Inbred F344
Tissue Distribution
Tomography, Emission-Computed
Tumor Cells, Cultured
Reg. No./Substance:
0/1-amino-3-fluoromethylcyclobutane-1-carboxylic acid; 0/Amino Acid Transport System A; 0/Amino Acid Transport System L; 0/Amino Acids; 0/Carboxylic Acids; 0/Cyclobutanes; 0/Fluorine Radioisotopes; 0/Ligands; 0/Propionic Acids; 0/Radiopharmaceuticals

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