Sestamibi is a substrate for MDR1 and MDR2 P-glycoprotein genes

Brigid Joseph, Kuldeep K. Bhargava, Harmeet Malhi, Michael L. Schilsky, Diwakar Jain, Christopher J. Palestro, Sanjeev Gupta

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


Technetium-99m sestamibi has attracted interest for assessment of the function of P-glycoproteins, which are well expressed in the liver and have roles in biliary transport and the removal of chemotherapeutic drugs. To further examine the cross-reactivity of 99mTc-sestamibi for P-glycoprotein family members, we conducted studies in animals. Hepatobiliary secretion of 99mTc-sestamibi was determined in normal FVB/N mice, mutant mice with specific P-glycoprotein deficiencies in the FVB/N background, normal Long-Evans Agouti (LEA) rats, and Long-Evans Cinnamon (LEC) rats with abnormal copper transport and liver disease but intact P-glycoprotein expression. After intrasplenic injection, 99mTc-sestamibi was rapidly incorporated in the mouse and rat liver, with maximal accumulation after 102±31 and 109±16 s, respectively (P=NS). In normal mice and rats, 55%±11% and 55%±6%, respectively, of the maximal sestamibi activity was retained in the liver after 1 h (P=NS). In double knockout mice lacking both mdr1a and mdr1b homologs of the human MDR1 (ABCB1) gene, 88%±11% of maximal sestamibi activity was retained in the liver after 1 h (P<0.001). In knockout mice deficient in either mdr1a gene or mdr2 (ABCB4) gene, biliary sestamibi excretion was also impaired, although this impairment was relatively less pronounced in ABCB4-deficient mice than in double knockout mice lacking both ABCB1 gene homologs (P<0.03). Hepatobiliary sestamibi excretion in LEC rats was not different from that in control normal rats, despite the presence of significant liver disease in the former. Hepatobiliary sestamibi excretion requires P-glycoproteins and is unperturbed in chronic liver disease. Sestamibi appears to be a substrate for both ABCB1 and ABCB4 genes, although the former utilizes it far more efficiently. Assessment of P-glycoprotein activity with sestamibi should consider how regulation of ABCB1 and related family members might modulate sestamibi incorporation.

Original languageEnglish (US)
Pages (from-to)1024-1031
Number of pages8
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Issue number7
StatePublished - Jul 1 2003


  • ABCB1 gene
  • ABCB4 gene
  • Liver
  • Mdr1 gene
  • Mdr2 gene
  • P-glycoprotein
  • Sestamibi

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging


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