Technetium-99m-hexakis-2-methoxyisobutylisonitrile scintigraphy and multidrug resistance-related protein expression in human primary lung cancer

Abstract

The occurrence of multidrug resistance (MDR) is a major cause of resistance to chemotherapeutic agents in patients with lung cancer, in part owing to the overexpression of MDR-related proteins. Technetium-99m-hexakis-2-methoxyisobutylisonitrile ((99m)Tc-MIBI) has been shown to be a substrate for some MDR-related proteins. The aim of this study is to evaluate the role of (99m)Tc-MIBI scintigraphy for functional imaging of MDR-related protein phenotypes. To determine the correlation between (99m)Tc-MIBI scintigraphy and the expression level of P-glycoprotein (Pgp), multidrug-resistance protein (MRP), and glutathione-S-transferase Pi (GSTpi), 26 patients (17 men and 9 women, median age 57.5 years) with primary lung cancer were investigated. Following intravenous administration of 925 MBq (99m)Tc-MIBI, single-photon emission computed tomography (SPECT) and computed tomography (CT) were performed at 15 min and 2 h. On the basis of the fused images, tumor to background (T/B) ratio of both early and delayed images, and washout rate (WR%) of (99m)Tc-MIBI were calculated. The immunohistochemical staining of Pgp, MRP, and GSTpi was performed, and the expression level was semiquantitated using a pathoimage analysis system. The imaging results were compared with the status of Pgp, MRP, and GSTpi expression. The WR% of (99m)Tc-MIBI showed a significant positive correlation with Pgp expression (r = 0.560, P = 0.003), as no correlation was observed between WR% and MRP or GSTpi (r = 0.354, P = 0.076; r = 0.324, P = 0.106). Neither early T/B nor delayed T/B correlated with the expression level of Pgp, MRP, and GSTpi. WR%, Pgp, and GSTpi expression showed significant differences between squamous cell carcinoma (group A) and adenocarcinoma (group B). There was no significant difference among Pgp, MRP, and GSTpi expression levels in any cases (P > 0.05). Our data confirmed that (99m)Tc-MIBI scintigraphy is useful for determining the MDR caused by Pgp in patients with primary lung cancer.