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

Philip H. Elsinga*, Eric J.F. Franssen, N. Harry Hendrikse, Lizette Fluks, Anne Miek A. Weemaes, Winette T.A. Van Der Graaf, Elisabeth G.E. De Vries, Gerben M. Visser, Willem Vaalburg

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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.

Original languageEnglish
Pages (from-to)1571-1575
Number of pages5
JournalJournal of Nuclear Medicine
Issue number9
Publication statusPublished - 1 Sep 1996

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