Experimental and clinical observations of 99mTc-MIBI uptake correlate with P-glycoprotein expression in lung cancer

Abstract

99mTc-methoxyisobutylisonitrile (99mTc-MIBI) has been used as a tumour positive scintigraphic agent for diagnostic purposes. However, the pharmaceutical kinetics and accumulation patterns of 99mTc-MIBI in tumour tissues (both in vitro and in vivo) remained poorly understood. Using human embryonic lung fibroblasts (HLFs) as a control, we investigated the kinetics of 99mTc-MIBI accumulation in four human cancer cell lines. We found that, among the tested groups, the uptake rate (UR) of 99mTc-MIBI in normal lung fibroblast cells was the lowest at 90 min after injection, while the UR of four groups of carcinoma cells increased significantly. A significant change of the UR value was observed under cellular depolarization and hyperpolarization. Interestingly, we found that malonic acid, a respiratory chain inhibitor, could inhibit UR rates by 27% from the lowered level in hyper-potassium condition. We also used a semi-quantitative method to analyse 99mTc-MIBI imaging results from 93 clinical cases of pathologically or cytologically confirmed lung cancer lesions. We found that the UR value of a lung benign lesion group was significantly lower than that of a malignant lesion group. We conclude that the sensitivity, specificity and accuracy of 99mTc-MIBI imaging for the lung occupied cancer lesions were 89.83%, 79.41% and 86.02%, respectively. We also investigated the relationship between P-gp expression and MIBI uptake in 25 clinical cases. These observations demonstrate a close relationship between the state of 99mTc-MIBI accumulation and the metabolic level of tumour cells and the P-gp expression. Our data suggest that 99mTcc-MIBI semi-quantitative imaging is useful for the qualitative diagnosis of lung-occupied cancer lesions and may be a potential predictor of the P-gp expression in the clinic.