The multidrug resistance of in vitro tumor cell lines derived from human breast carcinoma MCF-7 does not influence pentavalent technetium-99m-dimercaptosuccinic Acid uptake.
The main causes of multidrug resistance (MDR) are overexpression of P-glycoprotein (P-gp) and multidrug resistance-associated protein isoform 1 (MRP1) often associated with high levels of glutathione (GSH). We investigated whether MDR phenotype can influence Tc-99m-(V)-DMSA [pentavalent technetium-99m-dimercaptosuccinic acid] entry by comparing its uptake with that of Tc-99m-sestamibi (MIBI) on an in vitro model of sensitive (MCF-7) and variant resistant cell lines. Drug resistance was assessed by immunoblotting, GSH measurement, and 3-[4,5-dimethylthiazol-2-yl]-2,5,diphenyl tetrazolium bromide (MTT) assay. To correlate MDR phenotype with tracer accumulation, uptakes were performed with and without P-gp and MRP1 inhibitors and after GSH modulation. Similar accumulation of Tc-99m-(V)-DMSA was observed in all cell lines and the use of MDR reversals did not enhance its uptake. Our results demonstrate clearly that Tc-99m-(V)-DMSA uptake is not related to either P-gp and MRP1 expression, or GSH levels. In contrast, Tc-99m-MIBI accumulation is inversely proportional to the cell MDR phenotype. The combination of Tc-99m-(V)-DMSA and Tc-99m-MIBI may be a useful tool for noninvasive detection of malignant sites and their chemoresistance status.
Denoyer
Delphine
D
Department of Biophysics and Radiopharmaceuticals, Research group Cell Death and Neoplasia, Faculty of Medicine Jacques Lisfranc, Saint Etienne, France. delphine.denoyer@univ-st-etienne.fr
Perek
Nathalie
N
Le Jeune
Nathalie
N
Frère
Delphine
D
Dubois
Francis
F
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005978:Glutathione / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D019783:Technetium Tc 99m Dimercaptosuccinic Acid / Q000378:metabolism*; D017256:Technetium Tc 99m Sestamibi / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D019783:Technetium Tc 99m Dimercaptosuccinic Acid; D004317:Doxorubicin; D017256:Technetium Tc 99m Sestamibi; D005978:Glutathione