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.