Functional imaging of multidrug resistant phenotype by 99mTc-MIBI scan in patients with multiple myeloma

Overexpression of P-glycoprotein (Pgp) is one of the primary mechanisms of multidrug resistance (MDR) in several diseases, including multiple myeloma. The aim of this study was to investigate whether the washout of 99mTc-MIBI, a transport substrate of Pgp, is enhanced in the bone marrow of patients with multiple myeloma overexpressing Pgp. Seventeen (17) patients were i.v. injected with 555 MBq of 99mTc-MIBI, and whole-body scans were performed at 10 and 60 minutes. A region of interest (ROI) was drawn over the thoracic spine of each scan, and the washout of 99mTc-MIBI was calculated, after decay correction, as: (10-minute counts/pixel minus 60-minute counts/pixel) divided by 10-minute counts/pixel. Pgp expression was determined in 17 bone marrow samples obtained from the same patients immediately before the 99mTc-MIBI scan. Following centrifugation over the Ficoll-Hypaque gradient, cytospins were obtained and immunostained with C219 monoclonal antibody. The immunostaining of Pgp was graded as 1, 2, or 3 when a faint, moderate, or intense reaction, respectively, was observed in infiltrating plasma cells. Washout of 99mTc-MIBI ranged between 5% and 26%. A statistically significant direct correlation was found between the washout of the tracer and Pgp expression (Spearman rank correlation coefficient r = 0.74, p < 0.001). A partial overlap of washout values was observed in different classes of Pgp expression, thus preventing the discrimination of individual patients. Washout of 99mTc-MIBI, expressed as the percentage of radioactivity cleared from the bone marrow over a 1-hour period, may be used as a noninvasive tool for in vivo whole-body imaging of Pgp expression and function in multiple myeloma patients.