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In Vivo Distribution and Identification of ¹¹C-Activity After Injection of [Methyl-¹¹C]Thymidine in Wistar Rats

Institute for Nuclear Sciences, University of Gent, Flanders
Departments of Radiotherapy and Nuclear Medicine and Electronics and Information Systems, ELIS/MEDISIP, University of Gent, Flanders, Belgium

Correspondence: For correspondence or reprints contact: Patrick Goethals, MD, Institute for Nuclear Sciences, Proeftuinstraat 86, B-9000 Gent, Flanders, Belgium.

ABSTRACT

[Methyl-¹¹C]thymidine and PET offer an in vivo, noninvasive quantitative approach for studying nucleoside uptake in cells on the condition the fraction of [methyl-¹¹C]thymidine (in deoxyribonucleic acid [DNA] or as DNA precursors) versus the total accumulated activity is known. Methods: In a group of normal (n = 6) and a group of tumor-bearing (n = 3) Wistar rats, the biodistribution of ¹¹C-activity was studied dynamically. In a second group of rats (n = 6), the animals were killed at 20 min postinjection and the organs and tissues of interest (liver, heart, brain, duodenum and tumor) were measured for activity and then homogenized. ¹¹C-activity in each fraction (cell debris, protein/DNA-fraction, lipids and supernatant) was measured. The supernatant was analyzed by high-performance liquid chromatography (HPLC)-radiochromatography for identification of different ¹¹C-labeled compounds. Results: After venous injection, most of the ¹¹C-activity was rapidly trapped in the liver and in fast-dividing tissue (e.g., duodenum); minor activity was located in the bladder, kidneys, heart and brain. HPLC separation showed that the ¹¹C-activity of the liver tissue consisted of metabolites only. For the duodenum and tumor, at least 55% of the ¹¹C-activity was precipitated in the protein/DNA-fraction and about 60% as DNA precursors (thymidine, 2'-deoxythymidine 5'-monophosphate and 2'-deoxythymidine 5'-triphosphate ) in the supernatant. Conclusion: Despite the in vivo metabolism, major ¹¹C-activity in rapidly dividing tissue consists of [methyl-¹¹C]thymidine incorporated in the DNA. Catabolism takes place mainly in the liver where the degradation products are stored. PET quantification data using [methyl-¹¹C] thymidine can give information about thymidine incorporation in DNA and cell proliferation of tumors.

Key Words: [methyl-¹¹C]thymidine • PET • cell proliferation • tissues

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