European Journal of Nuclear Medicine Vol. 28, No. 9, September 2001 Abstract. The occurrence of multidrug resistance (MDR), which is in part due to the overexpression of P-glycopro- tein (Pgp), is a major problem in neoadjuvant therapy of malignant musculoskeletal tumours. The aim of this study was to investigate the role of technetium-99m hexakis-2-methoxyisobutylisonitrile ( 99m Tc-MIBI) scin- tigraphy for functional imaging of the MDR1 phenotype in patients with musculoskeletal sarcomas. We aimed to compare 99m Tc-MIBI uptake and washout kinetics with the expression of Pgp and with chemotherapy response. Twenty-five patients (16 males and 9 females, aged be- tween 8 and 65 years) with malignant musculoskeletal tumours were studied. After injection of 555–740 MBq 99m Tc-MIBI, dynamic flow images of the involved area were obtained for 3 min, and planar images were ac- quired at 10 min and 1 h. From the dynamic images, a tumour perfusion index (TPI) was obtained using Patlak- Rutland analysis. Tumour to background (T/B) ratios of both early and delayed images and percent wash-out rate (WR%) of 99m Tc-MIBI were calculated. Immunohisto- chemical analysis of Pgp was performed on biopsy spec- imens and the degree of expression was graded accord- ing to a semiquantitative scoring system, from 0 to 6. After neoadjuvant therapy, tumour response was as- sessed by examining the ratio of viable cells and by de- tecting percent necrosis. Scintigraphic results were com- pared with Pgp status and therapy response. Irrespective of the Pgp status, all patients showed significant perfu- sion and 99m Tc-MIBI uptake in early images. There was not a significant correlation 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<0.01), and the wash-out rate of 99m Tc-MIBI was significantly higher in patients with high Pgp ex- pression than in those with a low Pgp score (33%±9% vs 17%±9%). Therapy response was determined in 21 of 25 patients, and in only 5 of 21 cases was the percent ne- crosis more than 90%. Neither Pgp expression rate nor WR% was found to show a significant correlation with percent necrosis in the bulk tumour specimens. In con- clusion, the initial uptake of 99m Tc-MIBI in bone and soft tissue sarcomas did not correlate with Pgp expression. A relationship was found between the wash-out rate of 99m Tc-MIBI and the Pgp score, with a significant differ- ence in WR% being observed between patients with high and patients with low Pgp expression. Keywords: Technetium-99m hexakis-2-methoxyisobutyl- isonitrile – P-glycoprotein – Bone sarcoma – Soft tissue sarcoma – Multidrug resistance Eur J Nucl Med (2001) 28:1341–1350 DOI 10.1007/s002590100588 Introduction The survival rate among patients with musculoskeletal sarcomas is not encouraging despite the use of various combinations of chemotherapy agents in conjunction This work was presented in part at the annual meeting of EANM, October 1999, in Barcelona, Spain. Zeynep Burak ( ) Department of Nuclear Medicine, Ege University Medical Faculty, Bornova, 35100 I . zmir, Turkey e-mail: zburak@egenet.com.tr Fax: +90-232-3422142 Original article The role of 99m Tc-MIBI scintigraphy in the assessment of MDR1 overexpression in patients with musculoskeletal sarcomas: comparison with therapy response Zeynep Burak 1 , Özden Ersoy 2 , Jean-Luc Moretti 3 , Rüya Erinç 1 , Zehra Özcan 1 , Aysegül Dirlik 1 , Dündar Sabah 4 , Gülçin Basdemir 2 1 Department of Nuclear Medicine, Ege University Medical Faculty, Bornova, 35100 I . zmir, Turkey 2 Department of Pathology, Ege University Medical Faculty, I . zmir, Turkey 3 Service de Médecine Nucléaire et Biophysique, Hôpital Avicenne, CHU Bobigny, Université Paris XIII, France 4 Department of Orthopaedics, Ege University Medical Faculty, I . zmir, Turkey Received 5 February and in revised form 30 May 2001 / Published online: 10 July 2001 © Springer-Verlag 2001