Purpose: 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.
Materials and methods: 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.
Results: 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).
Conclusion: Tc-99m MIBI SPECT is useful for noninvasively predicting the presence of MDR1 gene-encoded P-glycoprotein in patients with hepatocellular carcinoma.