Multidrug resistance phenotype in leukaemic cells from patients with acutemyelocytic leukaemia can be detected with Tc-99(m)-MIBI

The aim of the study was to investigate whether Tc-99(m)-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 wi th acute myelocytic leukaemia (AML) were used, five with undetectable mdr1 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 d aunorubicin (Dnr), with and without 3 mu M CyA. The median Tc-99(m)-MIBI ac cumulation (% 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 med ian increase in Tc-99(m)-MIBI accumulation with CyA was 30% compared with t he mdr1-positive cells with a median increase of 242%, P = 0.009. CyA had n o significant effect on Dnr accumulation in four of the mdr1-negative sampl es. The median increase of Dnr accumulation in the mdr1-positive cells was 40%. The results show that Tc-99(m)-MIBI With a high sensitivity can detect rather low levels of mdr1 gene expression in clinical samples. Consequentl y, Tc-99(m)-MIBI scintigraphy has the potential to be used for monitoring t he effect of resistance modifiers on the accumulation and retention of cyto static drugs in human tumours in vivo.