The role of Tc-99m-MIBI scintigraphy in the assessment of MDR1 overexpression in patients with musculoskeletal sarcomas: comparison with therapy response

The occurrence of multidrug resistance (MDR), which is in part due to the o verexpression of P-glycoprotein (Pgp), is a major problem in neoadjuvant th erapy of malignant musculoskeletal tumours. The aim of this study was to in vestigate the role of technetium-99m hexakis-2-methoxyisobutylisonitrile (T c-99m-MIBI) scintigraphy for functional imaging of the MDR1 phenotype in pa tients with musculoskeletal sarcomas. We aimed to compare Tc-99m-MIBI uptak e and washout kinetics with the expression of Pgp and with chemotherapy res ponse. Twenty-five patients (16 males and 9 females, aged between 8 and 65 years) with malignant musculoskeletal tumours were studied. After injection of 555-740 MBq Tc-99m-MIBI, dynamic flow images of the involved area were obtained for 3 min, and planar images were acquired at 10 min and I h. From the dynamic images, a tumour perfusion index (TPI) was obtained using Patl ak-Rutland analysis. Tumour to background (T/B) ratios of both early and de layed images and percent wash-out rate (WR%) of Tc-99m-MIBI were calculated . Immunohistochemical analysis of Pgp was performed on biopsy specimens and the degree of expression was graded according to a semiquantitative scorin g system, from 0 to 6. After neoadjuvant therapy, tumour response was asses sed by examining the ratio of viable cells and by detecting percent necrosi s. Scintigraphic results were compared with Pgp status and therapy response . Irrespective of the Pgp status, all patients showed significant perfusion and Tc-99m-MIBI uptake in early images. There was not a significant correl ation between T/B ratios of early and delayed images and Pgp expression. We observed a positive correlation between WR% and Pgp status (r=0.61, P <0.0 1), and the wash-out rate of Tc-99m-MIBI was significantly higher in patien ts with high Pgp expression than in those with a low Pgp score (33%+/-9% vs 17%+/-9%). Therapy response was determined in 21 of 25 patients, and in on ly 5 of 21 cases was the percent necrosis more than 90%. Neither Pgp expres sion rate nor WR% was found to show a significant correlation with percent necrosis in the bulk tumour specimens. In conclusion, the initial uptake of Tc-99m-MIBI in bone and soft tissue sarcomas did not correlate with Pgp ex pression. A relationship was found between the wash-out rate of Tc-99m-MIBI and the Pgp score, with a significant difference in WR% being observed bet ween patients with high and patients with low Pgp expression.