99mTc-MIBI imaging as a predictor of therapy response in osteosarcoma compared with multidrug resistance-associated protein and P-glycoprotein expression.

Burak Z., Moretti J., Ersoy O., Sanli U., Kantar M., Tamgac F., ...More

Journal of nuclear medicine : official publication, Society of Nuclear Medicine, vol.44, pp.1394-401, 2003 (SCI-Expanded) identifier identifier identifier


In vitro studies have demonstrated that Tc-99m-methoxyisobutylisonitrile (Tc-99m-MIBI) is a transport substrate of multidrug resistance (MDR)-related proteins. The aim of this clinical study was to evaluate whether Tc-99m-MIBI scintigraphy was a functional imaging tool for in vivo detection of multidrug resistance-associated protein (MRP) expression in osteosarcoma and to investigate the role of MRP and Tc-99m-MIBI imaging to predict the clinical outcome. We also examined whether the scintigraphic parameters would help to distinguish the functional capacity of P-glycoprotein (Pgp) and MRP. Methods: Twenty-four patients with a diagnosis of osteosarcoma were studied before neoadjuvant chemotherapy. Tumor-to-background ratios of both early (10 min) and delayed (1 h) images and the percentage washout rate (WR%) of Tc-99m-MIBI were calculated. Immunohistochemical analysis of MRP and Pgp was performed on biopsy specimens, and the response to preoperative chemotherapy was assessed by histopathologic examination. Results: Fifteen of 24 osteosarcoma samples in our series (62.5%) showed significant expression of MRP. The level of MRP expression was significantly correlated with the WR% of Tc-99m-MIBI (r = 0.58, P = 0.003), and the WR% of Tc-99m-MIBI was significantly faster in patients with high MRP expression than in those with a low MRP score (P = 0.007). The clearance rate of Tc-99m-MIBI was significantly slower in tumor samples with negative or low expression of both Pgp and MRP (16% +/- 6.2%) when compared with osteosarcomas with high expression of both proteins (31.7% +/- 8.7%) (P = 0.001). There was not a significant difference between the WR% of 99mTc-MIBI in tumors with coexpression of both proteins and in tumors with high expression of either Pgp or MRP. Both the rate of MRP expression and the WR% of Tc-99m-MIBI were significantly correlated with response rate. Conclusion: Our results suggest that the WR% of Tc-99m-MIBI is correlated with MRP expression. Both the WR% of Tc-99m-MIBI and MRP expression are correlated with therapy response. Tc-99m-MIBI can be used as a general probe for functional imaging of both Pgp and MRP; however, it is not capable of differentiating the functional status of either MDR-related glycoprotein.