Using ~(99)Tc~m-MIBI to evaluate tumor multidrug resistance and monitor the reversing of chemosensitizer

Objective To study the correlation between uptake of 99 Tc m-methoxyisobutylisonitrile (MIBI) and multidrug-resistant P-glycoprotein (gp),and to evaluate the effect of chemosensitizer. Methods Tumor bearing mice model was established by implanting human cancer cell line MCF-7/Adr,the model mice were randomized into two groups: chemosensitizer verapamil group and control group. Before and after giving verapamil, 99 Tc m-MIBI imaging was performed at 15,60,90,120 min,respectively. Mice of the control group were sacrificed after the pre-verapamil imaging,and mice of the verapamil group were sacrificed after the post-verapamil imaging to get %ID/g of tumor and major organs. The level of P-gp was measured with immunocytochemical assay and mRNA of mdr1 gene determined with RT-PCR was obtained simultaneously. Results After giving verapamil the T/N ratio of tumor increased significantly except on 120 min imaging. 99 Tc m-MIBI uptake difference between the verapamil group and control group was obvious ( P =0.045,0.015,0.042,respectively). The expression of mdr1 mRNA decreased significantly after verapamil reversing( t =4.873,P =0.008). The level of P-gp declined from 0.1038±0.0078 to 0.0096±0.0059 ( t =3.579,P =0.023). The 99 Tc m-MIBI uptake of tumor,liver and kidney rose obviously after reversing,%ID/g increments were 106.83%, 40.35%,166.07%,respectively whereas it was slightly declined,-12.82%,in heart. Conclusion 99 Tc m-MIBI imaging may evaluate multidrug resistance (MDR) mediated by P-gp and be used to monitor the reversing effect of chemosensitizer in P-gp positive tumors.