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Expression of Multidrug Resistance Protein and Messenger RNA Correlate with ^99mTc-MIBI Imaging in Patients with Lung Cancer

Departments of Radiology and Pathology and Division of Tropical Medicine, Medical Research Institute, Kanazawa Medical University, Ishikawa, Japan

In vitro studies have shown that ^99mTc-sestamibi (MIBI) is a transport substrate for the P-glycoprotein (Pgp) pump and the multidrug resistance–associated protein (MRP) pump. However, whether MRP and lung resistance protein (LRP) affect tumor accumulation and efflux of ^99mTc-MIBI in lung cancer is not known. In this study, we explored whether Pgp and the other pumps, MRP and LRP, affect tumor accumulation and efflux of ^99mTc-MIBI in lung cancer. Methods: Thirty-four lung cancer patients who underwent surgery were examined. Before surgery, ^99mTc-MIBI SPECT was performed 15 min and 180 min after injection, and early uptake, delayed uptake (L/Nd), and washout rate (L/Nwr) of ^99mTc-MIBI were obtained. Pgp, MRP, and LRP expression were investigated by immunohistochemistry. The messenger RNA (mRNA) level of Pgp, MRP, and LRP was determined by real-time reverse-transcription polymerase chain reaction. The lung cancer ^99mTc-MIBI images were correlated with protein and mRNA expression. Results: The mean L/Nd of the Pgp (-) group was significantly higher than that of the Pgp (++) group (P = 0.0324). The Pgp (++) group had a higher L/Nwr than did the Pgp (-) group (P = 0.0269). The mean L/Nd of the Pgp mRNA low-expression group was significantly higher than that of the Pgp mRNA high-expression group (P = 0.0127). The Pgp mRNA high-expression group had a higher L/Nwr than did the Pgp mRNA low-expression group (P = 0.0825). No appreciable correlation was found between the lung cancer ^99mTc-MIBI images and the expression of MRP or LRP on the level of protein or mRNA. Conclusion: These data suggest that an increased level of Pgp expression correlates with a low accumulation on delayed scans and a high L/Nwr of ^99mTc-MIBI in lung cancer. Neither MRP nor LRP expression on the level of either protein or mRNA correlated significantly with tumor accumulation or efflux of ^99mTc-MIBI in lung cancer.

Key Words: ^99mTc-methoxyisobutylisonitrile • lung cancer • P-glycoprotein • multidrug resistance–associated protein • lung resistance protein

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