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[Methyl-carbon-11] thymidine for in vivo measurement of cell proliferation
P Goethals1, N Lameire, M van Eijkeren
1Laboratory of Analytical Chemistry, Institute for Nuclear Sciences, Gent University, Belgium.
Unlabelled:
[Methyl-11C]thymidine and PET provide an in vivo, noninvasive, quantitative approach for studying nucleoside uptake in cells on condition that the fraction of metabolites in the total accumulated activity is known.
Methods:
Using an animal model (Wistar rats), two independent approaches were followed. In the first approach, total accumulated activity in rapidly dividing tissue after intravenous injection of [methyl-11C]thymidine, respectively, [methyl-11C]thymine (first metabolite), was compared. In the second approach, the liver was surgically isolated to avoid thymidine catabolism.
Results:
After injection of [methyl-11C]thymidine, tissue activity consists of both labeled thymidine and metabolites, while after injection of [methyl-11C]thymine, it consists only of metabolites. The fraction of metabolites ranged from 9% to 44%. Comparing the specific activity with and without liver function yielded similar results. The calculated amount of metabolites was about 10%.
Conclusion:
In spite of the intense in vivo catabolism, major activity in rapidly dividing tissue consists of [methyl-11C]thymidine.