27 research outputs found

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

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    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 C-11 to probe P-gp with PET. Methods: Carbon-11-daunorubicin was prepared from (CCH2N2)-C-11 with an aldehyde precursor, followed by hydrolysis. Carbon-11-verapamil was synthesized by C-11-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 C-11-daunorubicin were prepared. Biodistribution studies of C-11-daunorubicin in male Wistar rats showed dose-dependent pharmacokinetics, whereas with C-11-verapamil the pharmacokinetics were dose independent. In in vitro experiments with cells, the ratio of accumulation of C-11-daunorubicin in drug sensitive/resistant cell lines was 16. Addition of verapamil resulted in increased accumulation of C-11-daunorubicin in the resistant cell line. The ratios of C-11-verapamil accumulation in drug-sensitive versus the MDR counterpart were 4-5. Conclusion: Carbon-11-daunorubicin and C-11-verapamil both have potential for in vivo probing of P-glycoprotein with PET
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