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Clinical Investigations |
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 resistanceassociated 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 resistanceassociated protein lung resistance protein
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