title: Carbon-11-labeled daunorubicin and verapamil for probing P-glycoprotein in tumors with PET.
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.
  
  
  CONCLUSIONS
  Carbon-11-daunorubicin and 11C-verapamil both have potential for in vivo probing of P-glycoprotein with PET.
authors.affiliation: PET Center, University Hospital, Groningen, The Netherlands.
authors.forename: P H
authors.initials: PH
authors.lastname: Elsinga
authors.forename: E J
authors.initials: EJ
authors.lastname: Franssen
authors.forename: N H
authors.initials: NH
authors.lastname: Hendrikse
authors.forename: L
authors.initials: L
authors.lastname: Fluks
authors.forename: A M
authors.initials: AM
authors.lastname: Weemaes
authors.forename: W T
authors.initials: WT
authors.lastname: van der Graaf
authors.forename: E G
authors.initials: EG
authors.lastname: de Vries
authors.forename: G M
authors.initials: GM
authors.lastname: Visser
authors.forename: W
authors.initials: W
authors.lastname: Vaalburg
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D003630:Daunorubicin / Q000493:pharmacokinetics; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008297:Male; D010051:Ovarian Neoplasms; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000493:pharmacokinetics
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D002250:Carbon Radioisotopes; D014700:Verapamil; D003630:Daunorubicin