Document Detail

A new 18F-labeled folic acid derivative with improved properties for the PET imaging of folate receptor-positive tumors.
MedLine Citation:
PMID:  20956469     Owner:  NLM     Status:  MEDLINE    
METHODS: The binding affinity of the cold reference compound 2'-fluorofolic acid was determined by in vitro displacement assays using human folate receptor-positive KB cells and (3)H-folic acid. (18)F labeling of 2'-fluorofolic acid was accomplished via a direct nucleophilic aromatic substitution of N(2)-(N,N-dimethylamino-methylene)-2'-nitrofolic acid di-tert-butylester followed by acidic cleavage of the amino and carboxylic protecting groups. The new radiofolate was evaluated in nude mice bearing KB tumor xenografts under control and blocking conditions. Animals were either scanned from 75 to 105 min after injection of the radiotracer or sacrificed 75 min after injection for ex vivo biodistribution studies.
RESULTS: 2'-fluorofolic acid showed a high binding affinity (inhibition constant, 1.8 ± 0.1 nM) for the folate receptor. Direct aromatic (18)F labeling of 2'-fluorofolic acid was achieved within 80 min via a convenient 2-step procedure in satisfactory radiochemical yields. The new radiotracer exhibited excellent pharmacokinetics with fast renal clearance and only moderate hepatobiliary elimination. Uptake of 2'-(18)F-fluorofolic acid in folate receptor-positive KB tumors was high and specific, allowing a clear-cut visualization by PET.
CONCLUSION: 2'-(18)F-fluorofolic acid, obtained via an integrated approach, is a promising PET agent for folate receptor-positive tumors and outperforms previously reported (18)F-labeled folates.
Tobias L Ross; Michael Honer; Cristina Müller; Viola Groehn; Roger Schibli; Simon M Ametamey
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Publication Detail:
Type:  Journal Article     Date:  2010-10-18
Journal Detail:
Title:  Journal of nuclear medicine : official publication, Society of Nuclear Medicine     Volume:  51     ISSN:  1535-5667     ISO Abbreviation:  J. Nucl. Med.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-05     Completed Date:  2010-12-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0217410     Medline TA:  J Nucl Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1756-62     Citation Subset:  IM    
Animal Imaging Center-PET, Center for Radiopharmaceutical Science of ETH, PSI, and USZ, Institute of Pharmaceutical Science, ETH Zürich, Zürich, Switzerland.
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MeSH Terms
Biological Transport / drug effects
Fluorine Radioisotopes / diagnostic use*
Folate Receptor 1 / metabolism*
Folic Acid / analogs & derivatives*,  diagnostic use*,  metabolism,  physiology
Folic Acid Antagonists / pharmacology
Gene Expression Regulation, Neoplastic
Glutamates / pharmacology
Guanine / analogs & derivatives,  pharmacology
Hydrophobic and Hydrophilic Interactions
KB Cells
Kidney / drug effects,  metabolism
Neoplasms / genetics,  metabolism*,  radionuclide imaging*
Positron-Emission Tomography / methods*
Staining and Labeling
Substrate Specificity
Reg. No./Substance:
0/Fluorine Radioisotopes; 0/Folate Receptor 1; 0/Folic Acid Antagonists; 0/Glutamates; 0/Ligands; 137281-23-3/pemetrexed; 59-30-3/Folic Acid; 73-40-5/Guanine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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