Abstract
Imaging with (99m)Tc-sestamibi ((99m)Tc-MIBI) has been used to assess 170-kDa P-glycoprotein (P-gp) expression and predict chemotherapy responses in several types of malignancy, such as breast and lung cancers. The purpose of this study was to evaluate the relationship between (99m)Tc-MIBI accumulation in tumors and sensitivity to chemotherapy in gastric cancer patients. Thirty-six patients with advanced gastric cancer underwent (99m)Tc-MIBI scintigraphy before chemotherapy. Patients also underwent endoscopic biopsy, and the expression of P-gp or multidrug resistance-associated protein was analyzed by immunohistochemical staining. The relationship between the accumulation of (99m)Tc-MIBI in tumors and responses to chemotherapy with 5-fluorouracil/cis-diamminedichloroplatinum(II) or epirubicin was examined. Higher accumulation of (9m)Tc-MIBI in tumors was observed in 25 and 23 of 36 gastric cancer patients at the early (30 min) and delayed (120 min) images, respectively. Accelerated accumulation of (99m)Tc-MIBI negatively correlates with increased expression of P-gp, but not of multidrug resistance-associated protein, as determined by immunohistochemistry in gastric cancer tissues. The response rate to 5-fluorouracil/cis-diamminedichloroplatinum(II) chemotherapy in patients with high (99m)Tc-MIBI accumulation (15.4%) was much lower than that in patients with low (99m)Tc-MIBI accumulation (54.5%). In contrast, patients with high (99m)Tc-MIBI accumulation show a higher response rate (41.7%) to chemotherapy with epirubicin, which is known to be a substrate of P-gp transporter. (99m)Tc-MIBI scintigraphy is useful to suggest the responses to chemotherapy of patients with advanced gastric cancer.
Highlights
Multidrug resistance is the major barrier to efficient chemotherapy of cancer
Accelerated accumulation of 99mTcMIBI negatively correlates with increased expression of P-gp, but not of multidrug resistance-associated protein, as determined by immunohistochemistry in gastric cancer tissues
It is well known that tumor cells that have become resistant to one type of anticancer drug acquire cross-resistance to other anticancer drugs with completely different structures
Summary
Multidrug resistance is the major barrier to efficient chemotherapy of cancer. Causes of chemotherapy failure are multifactorial, including the physical inability of drugs to reach malignant cells because of poor tumor vascularization and diverse cellular mechanisms lowering intracellular drug concentration or altering the ability of the drugs to affect their targets [1]. Significant correlations have been reported between 99mTc-MIBI scintigraphy and P-gp immunohistochemistry, in vitro cytotoxicity assay, chemotherapy response, and/or patient outcome in several types of malignancy, including breast cancer [13], lung cancer (14 –16), hepatocellular carcinoma [17], malignant lymphoma [18], soft tissue sarcoma, and bone sarcoma [19]. Imaging with 99mTc-MIBI can evaluate entire tumors and may provide a number of advantages to assess P-gp expression and predict chemotherapy responses. Of note, it can be performed noninvasively, allowing for sequential evaluation of P-gp expression and function through repeated assessment at different time points
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