Document Detail


[18F]fluoromethyl-[1,2-2H4]-choline: a novel radiotracer for imaging choline metabolism in tumors by positron emission tomography.
MedLine Citation:
PMID:  19773436     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Current radiotracers for positron emission tomography imaging of choline metabolism have poor systemic metabolic stability in vivo. We describe a novel radiotracer, [(18)F]fluoromethyl-[1,2-(2)H(4)]-choline (D4-FCH), that employs deuterium isotope effect to improve metabolic stability. D4-FCH proved more resistant to oxidation than its nondeuterated analogue, [(18)F]fluoromethylcholine, in plasma, kidneys, liver, and tumor, while retaining phosphorylation potential. Tumor radiotracer levels, a determinant of sensitivity in imaging studies, were improved by deuterium substitution; tumor uptake values expressed as percent injected dose per voxel at 60 min were 7.43 +/- 0.47 and 5.50 +/- 0.49 for D4-FCH and [(18)F]fluoromethylcholine, respectively (P = 0.04). D4-FCH was also found to be a useful response biomarker. Treatment with the mitogenic extracellular kinase inhibitor PD0325901 resulted in a reduction in tumor radiotracer uptake that occurred in parallel with reductions in choline kinase A expression. In conclusion, D4-FCH is a very promising metabolically stable radiotracer for imaging choline metabolism in tumors.
Authors:
Julius Leyton; Graham Smith; Yongjun Zhao; Meg Perumal; Quang-De Nguyen; Edward Robins; Erik Arstad; Eric O Aboagye
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-09-22
Journal Detail:
Title:  Cancer research     Volume:  69     ISSN:  1538-7445     ISO Abbreviation:  Cancer Res.     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-10-02     Completed Date:  2009-12-03     Revised Date:  2013-03-27    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7721-8     Citation Subset:  IM    
Affiliation:
Molecular Therapy Group, Faculty of Medicine, Imperial College London, London, United Kingdom.
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MeSH Terms
Descriptor/Qualifier:
Animals
Benzamides / pharmacology
Choline / analogs & derivatives*,  diagnostic use,  metabolism*,  pharmacokinetics
Colonic Neoplasms / metabolism,  radionuclide imaging*
Deuterium / diagnostic use*,  pharmacokinetics
Diphenylamine / analogs & derivatives,  pharmacology
HCT116 Cells
Humans
Melanoma / metabolism,  radionuclide imaging*
Mice
Mice, Inbred BALB C
Mice, Nude
Oxidation-Reduction
Positron-Emission Tomography / methods
Radiopharmaceuticals / diagnostic use*,  pharmacokinetics
Tissue Distribution
Transplantation, Heterologous
Grant Support
ID/Acronym/Agency:
A10337//Cancer Research UK; U1200.005.00001.01//Medical Research Council; //Cancer Research UK
Chemical
Reg. No./Substance:
0/Benzamides; 0/PD 0325901; 0/Radiopharmaceuticals; 0/fluoromethylcholine; 122-39-4/Diphenylamine; 62-49-7/Choline; 7782-39-0/Deuterium
Comments/Corrections

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