title: The role of 99mTc-MIBI scintigraphy in the assessment of MDR1 overexpression in patients with musculoskeletal sarcomas: comparison with therapy response.
abstract: The occurrence of multidrug resistance (MDR), which is in part due to the overexpression of P-glycoprotein (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 (99mTc-MIBI) scintigraphy for functional imaging of the MDR1 phenotype in patients with musculoskeletal sarcomas. We aimed to compare 99mTc-MIBI uptake and washout kinetics with the expression of Pgp and with chemotherapy response. 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 99mTc-MIBI, dynamic flow images of the involved area were obtained for 3 min, and planar images were acquired 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 99mTc-MIBI were calculated. Immunohistochemical analysis of Pgp was performed on biopsy specimens and the degree of expression was graded according to a semiquantitative scoring system, from 0 to 6. After neoadjuvant therapy, tumour response was assessed by examining the ratio of viable cells and by detecting percent necrosis. Scintigraphic results were compared with Pgp status and therapy response. Irrespective of the Pgp status, all patients showed significant perfusion and 99mTc-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 99mTc-MIBI was significantly higher in patients 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 only 5 of 21 cases was the percent necrosis 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 conclusion, the initial uptake of 99mTc-MIBI in bone and soft tissue sarcomas did not correlate with Pgp expression. A relationship was found between the wash-out rate of 99mTc-MIBI and the Pgp score, with a significant difference in WR% being observed between patients with high and patients with low Pgp expression.
authors.affiliation: Department of Nuclear Medicine, Ege University Medical Faculty, Bornova, Izmir, Turkey. zburak@egenet.com.tr
authors.forename: Z
authors.initials: Z
authors.lastname: Burak
authors.forename: O
authors.initials: O
authors.lastname: Ersoy
authors.forename: J L
authors.initials: JL
authors.lastname: Moretti
authors.forename: R
authors.initials: R
authors.lastname: Erinç
authors.forename: Z
authors.initials: Z
authors.lastname: Ozcan
authors.forename: A
authors.initials: A
authors.lastname: Dirlik
authors.forename: D
authors.initials: D
authors.lastname: Sabah
authors.forename: G
authors.initials: G
authors.lastname: Basdemir
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000737:chemistry / Q000000981:diagnostic imaging* / Q000628:therapy; D002648:Child; D018432:Drug Resistance, Multiple; D005260:Female; D018219:Histiocytoma, Benign Fibrous / Q000737:chemistry / Q000000981:diagnostic imaging / Q000628:therapy; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D019042:Muscle Neoplasms / Q000737:chemistry / Q000000981:diagnostic imaging* / Q000628:therapy; D020360:Neoadjuvant Therapy; D012516:Osteosarcoma / Q000737:chemistry / Q000000981:diagnostic imaging / Q000628:therapy; D010641:Phenotype; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D012509:Sarcoma / Q000737:chemistry / Q000000981:diagnostic imaging* / Q000628:therapy; D017256:Technetium Tc 99m Sestamibi
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D019275:Radiopharmaceuticals; D017256:Technetium Tc 99m Sestamibi