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

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Abstract

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
Volume37
Issue number9
Publication statusPublished - 1 Sept 1996

Keywords

  • PET
  • carbon-11-daunorubicin
  • carbon-11-verapamil
  • multidrug resistance

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