Factors influencing [F-18] 2-fluoro-2-deoxy-D-glucose (F-18 FDG) accumulation in melanoma cells: is FDG a substrate of multidrug resistance (MDR)?
In order to specify the influence of multidrug-resistance (MDR) on the accumulation of the PET tracer, F-18 FDG ([Fluorine-18] 2-fluoro-2-deoxy-D-glucose, in melanoma cells, both the MDR function and expression of two human melanoma cell lines SK-MEL 23 and 24, were evaluated. The effects of MDR modulators on FDG accumulation and efflux were also investigated. A functional analysis using representative MDR fluorescent substrates and inhibitors clarified the following characteristics: 1) SK-MEL 23 possesses a highly active function of MRP, but not P-gp. 2) SK-MEL 24 possesses weak functions of both MRP and P-gp. Western blot analysis using monoclonal antibodies for MDR expression demonstrated an exceedingly high MRP expression of SK-MEL 23 and only slight P-gp and MRP expression of SK-MEL 24, corresponding to the functional data. The efflux inhibition assay using F-18 FDG revealed a considerable retention of FDG in SK-MEL 23 in the presence of the MRP inhibitor probenecid. It was also found that the P-gp inhibitor verapamil depressed the FDG efflux of SK-MEL 24. Our present in vitro study suggests that FDG may be a substrate of MDR in some melanoma cells and further MDR may be one of the important factors affecting FDG-PET melanoma imaging.
Yamada
Kiyoshi
K
Department of Internal Medicine 1, Hematology/Oncology, Freiburg University Medical Center, Hugstetter str. 55, 79106 Freiburg i. Br., Germany.
Brink
Ingo
I
Engelhardt
Rupert
R
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D001682:Biological Availability; D015153:Blotting, Western; D004347:Drug Interactions; D018432:Drug Resistance, Multiple; D019788:Fluorodeoxyglucose F18 / Q000494:pharmacology*; D006801:Humans; D008544:Melanocytes / Q000187:drug effects* / Q000502:physiology*; D008545:Melanoma / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology; D049268:Positron-Emission Tomography; D011336:Probability; D012016:Reference Values; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured
D019788:Fluorodeoxyglucose F18