Carbon-11-labeled daunorubicin and verapamil for probing P-glycoprotein in tumors with PET

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. Methods: 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. Results: 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. Conclusion: Carbon-11-daunorubicin and ¹¹C-verapamil both have potential for in vivo probing of P-glycoprotein with PET.