Multidrug resistance phenotype in leukaemic cells from patients with acute myelocytic leukaemia can be detected with 99Tc(m)-MIBI.
The aim of the study was to investigate whether 99Tc(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 with 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 99Tc(m)-MIBI, or with daunorubicin (Dnr), with and without 3 microM CyA. The median 99Tc(m)-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 99Tc(m)-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 99Tc(m)-MIBI with a high sensitivity can detect rather low levels of mdr1 gene expression in clinical samples. Consequently, 99T(c)m-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.
Department of Hematology and Infectious Diseases, Karolinska Hospital, Stockholm, Sweden.
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A
Gruber
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I
Areström
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D
Xu
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J
Liliemark
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SA
Larsson
H
H
Jacobsson
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000502:physiology*; D003630:Daunorubicin / Q000493:pharmacokinetics; D018432:Drug Resistance, Multiple; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D017256:Technetium Tc 99m Sestamibi; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D017256:Technetium Tc 99m Sestamibi; D003630:Daunorubicin