| Autor: |
Elsinga, PH, Franssen, EJF, Hendrikse, NH, Fluks, L, Weemaes, AMA, vanderGraaf, WTA, deVries, GE, Visser, GM, Vaalburg, W |
| Přispěvatelé: |
Guided Treatment in Optimal Selected Cancer Patients (GUTS) |
| Jazyk: |
angličtina |
| Rok vydání: |
1996 |
| Předmět: |
|
| Zdroj: |
Journal of Nuclear Medicine, 37(9), 1571-1575. SOC NUCLEAR MEDICINE INC |
| ISSN: |
0161-5505 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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