Assessment of 99mTc-MIBI SPECT(/CT) to monitor multidrug resistance-related proteins and apoptosis-related proteins in patients with ovarian cancer: a preliminary study

Abstract

Multidrug resistance (MDR) has been suggested to be a major cause of failure of chemotherapy treatment for cancer. It is associated with the expression of MDR-related and apoptosis-related proteins. Recently, technetium-99m hexakis 2-methoxyisobutylisonitrile ((99m)Tc-MIBI) has been suggested as a tumor-seeking agent for the detection of MDR. The aim of this study was to evaluate (99m)Tc-MIBI single-photon emission computed tomography (SPECT)(/CT) for functional imaging of MDR-related and apoptosis-related proteins in patients with ovarian cancer. Eleven women (mean age 63 years, range 53-76) with a clinical suspicion of ovarian cancer were prospectively studied. All patients were examined with (99m)Tc-MIBI imaging before surgery. After intravenous injection of 740 MBq (99m)Tc-MIBI, SPECT(/CT) imaging at 10 min and 2 h was performed. Based on the semiquantitative analysis of (99m)Tc-MIBI SPECT(/CT), both early and delayed tumor uptake ratios and washout rate % were calculated. The expression of MDR-related and apoptosis-related proteins was assessed in surgically excised tumors. Immunohistochemical staining was performed to quantify the expression levels of multidrug resistance protein 1 (MDR1), multidrug resistance-associated protein1 (MRP1), MRP3, lung resistance protein (LRP), breast cancer resistance protein (BCRP), Y-box-binding protein-1 (YB-1), Bcl-2, Bax and glutathione-S-transferase. (99m)Tc-MIBI imaging results and immunohistochemical results were compared. Laparotomy was performed in all patients. Six ovarian cancers were proven by histopathological examination. Five of the six ovarian cancers were positive for (99m)Tc-MIBI uptake on both early and delayed images with (99m)Tc-MIBI SPECT(/CT). MDR-related and apoptosis-related proteins were found to be expressed in all tumors. For the five positive (99m)Tc-MIBI uptake cases, the washout rate % of (99m)Tc-MIBI uptake showed a significant positive correlation with the expression of YB-1 (r = 0.988, P = 0.0015), and the early tumor uptake ratio showed a significant positive correlation with the expression of Bax (r = 0.882, P = 0.047). Our results suggested that (99m)Tc-MIBI SPECT(/CT) might be a valuable diagnostic imaging technique to evaluate MDR-associated YB-1 and Bax-mediated apoptosis in patients with ovarian cancer.