Multidrug resistance phenotype in leukaemic cells from patients with acute myelocytic leukaemia can be detected with 99Tcm-MIBI

Abstract

The aim of the study was to investigate whether 99Tcm-MIBI (Cardiolite), recently shown to be a substrate for P-glycoprotein, has the potential to be used as a marker for mdr1 gene expression and whether cyclosporin A (CyA) can modify its accumulation in vivo. Leukaemic cells from ten patients with acute myelocytic leukaemia (AML) were used, five with undetectable mdrl gene expression and five with mdr1 mRNA levels ranging from 1.0 to 3.8 mdr1 mRNA transcripts per cell. Cells were incubated with 99Tcm-MIBI, or with daunorubicin (Dnr), with and without 3 μM CyA. The median 99Tcm-MIBI accumulation (% of added radioactivity) in mdr1-negative cells was 0.89% and in the mdr1-positive cells 0.34%, P = 0.01. In mdr1-negative cells, the median increase in 99Tcm-MIBI accumulation with CyA was 30% compared with the mdr1-positive cells with a median increase of 242%, P = 0.009. CyA had no significant effect on Dnr accumulation in four of the mdr1-negative samples. The median increase of Dnr accumulation in the mdr1-positive cells was 40%. The results show that 99Tcm-MIBI with a high sensitivity can detect rather low levels of mdr1 gene expression in clinical samples. Consequently, 99Tcm-MIBI scintigraphy has the potential to be used for monitoring the effect of resistance modifiers on the accumulation and retention of cytostatic drugs in human tumours in vivo. © 1998 Cancer Research Campaign.