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Unlabelled: We prospectively studied 48 patients with either breast cancer (30 patients) or lung cancer (18 patients) to ascertain the relationship between the degree of accumulation of 99mTc-sestamibi and the expression of p-glycoprotein in tumor tissues., Methods: During initial presentation (37 patients) or post-therapy evaluation (11 patients), the patients underwent contemporaneous 99mTc-sestamibi imaging and biopsy (30 patients) or surgery (18 patients). The interval between surgery/biopsy and imaging varied between 3 and 15 days. All patients had radiologically detectable tumors. Immunohistochemical studies were performed on paraffin sections using a monoclonal antibody, JSB-1, developed against the internal epitope of p-glycoprotein. Tumor-to-background ratios were correlated with the level of p-glycoprotein expression determined by immunohistochemical studies., Results: Our results showed an inverse correlation between the tumor-to-background ratios of 99mTc-sestamibi and the density of p-glycoprotein expression in tumor tissues. The values for the tumor-to-background ratios were significantly lower for those tumors expressing p-glycoprotein at high levels than those with scattered and no expression (p < 0.01 and p < 0.001, respectively)., Conclusion: Although our results warrant further studies at the molecular level using PCR techniques after the extraction of mRNA, our data strongly suggest that 99mTc-sestamibi imaging is useful to noninvasively determine the presence of multidrug resistance in patients with malignant tumors.