Vander Borght T M, Lambotte L E, Pauwels S A, Dive C C
Department of Gastroenterology, University of Louvain, Brussels, Belgium.
Hepatology. 1990 Jul;12(1):113-8. doi: 10.1002/hep.1840120118.
Noninvasive measurement of liver regeneration with positron emission tomography has been attempted with 11C-thymidine; however, results were unsatisfactory using thymidine labeled on its methyl group. To evaluate whether the specificity of the method could be improved by modifying the labeling position of the tracer, thymidine labeled on its methyl group with 3H and thymidine labeled on its carbon 2 with 14C were injected in 22 hepatectomized rats either 1 hr (when DNA synthesis is not increased) or 24 hr after the surgical procedure (when the rate of DNA synthesis is maximal). Liver samples taken 10, 30 and 120 min after injection showed that, in contrast to 3H-radioactivity, 14C-radioactivity measured in whole tissue allowed a clear discrimination between regenerating and nonregenerating livers. In addition, 14C-radioactivity measured in whole tissue of regenerating livers correlated with the DNA radioactivity 10, 30 and 120 min after injection of the tracer. In contrast, no such correlation was found with the methyl-labeled thymidine. Analysis of the radioactive material present in the non-DNA fraction using ion exchange disks and high-performance liquid chromatography showed that 2-C-labeled thymidine was incorporated into DNA without accumulation of labeled metabolites whereas, for the methyl-labeled thymidine, almost all radioactivity was related to degradative products. Therefore the evaluation of the liver regeneration with the 2-C-labeled thymidine, which does not require cellular fractionation, should be suited for noninvasive measurement with positron emission tomography.
人们曾尝试用11C-胸腺嘧啶核苷通过正电子发射断层扫描对肝脏再生进行无创测量；然而，使用甲基标记的胸腺嘧啶核苷时结果并不理想。为了评估通过改变示踪剂的标记位置能否提高该方法的特异性，将3H标记在甲基上的胸腺嘧啶核苷和14C标记在碳2上的胸腺嘧啶核苷分别注射到22只肝切除大鼠体内，注射时间为手术后1小时（此时DNA合成未增加）或24小时（此时DNA合成速率最大）。注射后10、30和120分钟采集的肝脏样本显示，与3H放射性不同，全组织中测量的14C放射性能够清晰区分再生肝脏和非再生肝脏。此外，再生肝脏全组织中测量的14C放射性与注射示踪剂后10、30和120分钟时的DNA放射性相关。相比之下，甲基标记的胸腺嘧啶核苷未发现这种相关性。使用离子交换盘和高效液相色谱对非DNA部分中存在的放射性物质进行分析表明，2-C标记的胸腺嘧啶核苷被掺入DNA中，且无标记代谢物积累，而对于甲基标记的胸腺嘧啶核苷，几乎所有放射性都与降解产物有关。因此，用2-C标记的胸腺嘧啶核苷评估肝脏再生，无需细胞分级分离，应适合用正电子发射断层扫描进行无创测量。
