Verapamil decreases accumulation of 99Tcm-MIBI and 99Tcm-tetrofosmin in human breast cancer and soft tissue sarcoma cell lines.
99Tcm-methoxyisobutylisonitrile (99Tcm-MIBI) and 99Tcm-tetrofosmin are cationic tracers recognized by the efflux pump P-glycoprotein (Pgp). Verapamil has been shown to be a competitive inhibitor of Pgp, and was one of the first multidrug-resistant reversing agents identified. The aim of this preclinical in vitro study was to evaluate the effects of verapamil on the accumulation of 99Tcm-MIBI and 99Tcm-tetrofosmin in the human breast cancer cell lines MCF-7 and SK-BR-3 and in the human soft tissue sarcoma cell lines SW 982 and SW 1353, in comparison with respective control cells, i.e. without preincubation with verapamil. After preincubation with 10 or 100 microM of verapamil for 15 or 30 min, the 99Tcm-MIBI and 99Tcm-tetrofosmin accumulation in cells was assessed at 10, 30 and 60 min after incubation with these tracers. Addition of verapamil caused a decline in the accumulation of the two tracers at all incubation times, as compared with control cells. These effects of verapamil were neither dose- nor preincubation time-dependent in most cells. Our data indicate that verapamil is not a promising agent for increasing the sensitivity of scintigraphy with 99Tcm-MIBI or 99Tcm-tetrofosmin, or for evaluating Pgp tumour status in these types of tumours.
Rodrigues
M
M
Department of Nuclear Medicine, University Hospital, Vienna, Austria. margarida.rodrigues@akh-wien.ac.at
Kalinowska
W
W
Zielinski
C
C
Sinzinger
H
H
D000230:Adenocarcinoma / Q000000981:diagnostic imaging* / Q000473:pathology; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival; D005260:Female; D006801:Humans; D009943:Organophosphorus Compounds / Q000493:pharmacokinetics*; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D012509:Sarcoma / Q000000981:diagnostic imaging*; D012983:Soft Tissue Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D017256:Technetium Tc 99m Sestamibi / Q000493:pharmacokinetics*; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D009943:Organophosphorus Compounds; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C078700:technetium tc-99m tetrofosmin; D017256:Technetium Tc 99m Sestamibi; D014700:Verapamil