In vivo distribution and identification of 11C-activity after injection of [methyl-11C]thymidine in Wistar rats.

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. 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. 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. 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.