Tc-99m MIBI SPECT is useful for noninvasively predicting the presence of MDR1 gene-encoded P-glycoprotein in patients with hepatocellular carcinoma.

Abstract

Resistance to chemotherapeutic drugs continues to be one of the major unsolved problems in the treatment of cancer. Multidrug resistance is defined as the ability of cells exposed to a single drug to develop resistance to a broad range of structurally and functionally unrelated drugs as a result of enhanced outward transport of drugs mediated by P-glycoprotein that is encoded by multidrug resistance genes. Recent evidence has shown that Tc-99m MIBI is a suitable transport substrate for P-glycoprotein. A potential advantage of Tc-99m MIBI SPECT is its superiority to diagnose noninvasively the presence of P-glycoprotein overexpression in vivo. In this study, the authors determined the association of enhanced MIBI efflux in Tc-99m MIBI SPECT with overexpression of P-glycoprotein in hepatocellular carcinoma. Thirty-five patients with hepatocellular carcinoma were enrolled in the study. Tc-99m MIBI SPECT was performed 10 minutes after intravenous injection of 20 mCi Tc-99m MIBI. All patients had liver biopsy or surgery within 1 week of MIBI imaging. Immunohistochemical study of the biopsy or resected hepatocellular carcinoma specimens was performed using the avidin-biotin-peroxidase technique with monoclonal antibody JSB-1 directed against P-glycoprotein. On Tc-99m MIBI SPECT, 30 of 35 (85.7%) patients with hepatocellular carcinoma had no Tc-99m MIBI uptake in tumor lesions, whereas five patients with hepatocellular carcinoma had Tc-99m MIBI uptake in tumor lesions. P-glycoprotein expression was observed in tumor tissues of all the patients without Tc-99m MIBI uptake, whereas among the five patients with Tc-99m MIBI uptake, no P-glycoprotein expression was seen in tumor lesions (P < 0.015). Tc-99m MIBI SPECT is useful for noninvasively predicting the presence of MDR1 gene-encoded P-glycoprotein in patients with hepatocellular carcinoma.