Elsinga P H, Franssen E J, Hendrikse N H, Fluks L, Weemaes A M, van der Graaf W T, de Vries E G, Visser G M, Vaalburg W
PET Center, University Hospital, Groningen, The Netherlands.
J Nucl Med. 1996 Sep;37(9):1571-5.
One of the mechanisms for multidrug resistance (MDR) of tumors is an overexpression of the P-glycoprotein (P-gp). The cytostatic agent daunorubicin and the modulator verapamil were labeled with 11C to probe P-gp with PET.
Carbon-11-daunorubicin was prepared from 11CCH2N2 with an aldehyde precursor, followed by hydrolysis. Carbon-11-verapamil was synthesized by 11C-methylation. Both tracers were evaluated by investigating pharmacokinetics in rats and in vitro cell kinetics using human ovarian carcinoma cells.
Amounts of 111 MBq 11C-daunorubicin were prepared. Biodistribution studies of 11C-daunorubicin in male Wistar rats showed dose-dependent pharmacokinetics, whereas with 11C-verapamil the pharmacokinetics were dose independent. In in vitro experiments with cells, the ratio of accumulation of 11C-daunorubicin in drug sensitive/resistant cell lines was 16. Addition of verapamil resulted in increased accumulation of 11C-daunorubicin in the resistant cell line. The ratios of 11C-verapamil accumulation in drug-sensitive versus the MDR counterpart were 4-5.
Carbon-11-daunorubicin and 11C-verapamil both have potential for in vivo probing of P-glycoprotein with PET.
肿瘤多药耐药（MDR）的机制之一是P-糖蛋白（P-gp）的过表达。用11C标记细胞抑制剂柔红霉素和调节剂维拉帕米，以通过正电子发射断层扫描（PET）探测P-gp。
用醛前体从11CCH2N2制备11C-柔红霉素，随后进行水解。通过11C-甲基化合成11C-维拉帕米。通过研究大鼠体内药代动力学以及使用人卵巢癌细胞进行体外细胞动力学研究，对这两种示踪剂进行评估。
制备了111 MBq的11C-柔红霉素。11C-柔红霉素在雄性Wistar大鼠中的生物分布研究显示出剂量依赖性药代动力学，而11C-维拉帕米的药代动力学与剂量无关。在细胞体外实验中，11C-柔红霉素在药物敏感/耐药细胞系中的积累比值为16。加入维拉帕米导致11C-柔红霉素在耐药细胞系中的积累增加。11C-维拉帕米在药物敏感细胞与多药耐药细胞中的积累比值为4-5。
11C-柔红霉素和11C-维拉帕米都有通过PET在体内探测P-糖蛋白的潜力。
