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Öğe The role of Tc-99(m)-sestamibi scintigraphy in the staging and prediction of the therapeutic response of stage IV neuroblastoma: Comparison with I-131-MIBG and Tc-99(m)-MDP scintigraphy(Lippincott Williams & Wilkins, 1999) Burak, Z; Yuksel, DA; Cetingul, N; Kantar, M; Ozkilic, H; Moretti, JLIn this study, we investigated prospectively the diagnostic role of Tc-99(m)-MIBI for staging and for predicting the therapeutic response of stage nr neuroblastoma compared wth I-131-MIBG imaging and Tc-99(m)- MDP bone scintigraphy. Nine patients (4 girls and 5 boys aged 1-7 years) with suspected or proven stage IV neuroblastoma were studied with Tc-99(m)-MIBI at initial diagnosis and after 12-18 months of multidrug therapy. After the injection of 80 MBq.kg(-1) Tc-99(m)-MIBI, early (10 min) and delayed (1 h) images were obtained. The data were correlated with I-131-MIBG scans, bone scintigraphy, ultrasound, computed tomography and/or magnetic resonance imaging, and bone marrow biopsy. Eight of nine primary tumours and 41 metastatic lesions were detected by I-131-MIBG scintigraphy. None of the primary lesions demonstrated significant Tc-99(m)-MIBI accumulation. Sestamibi was positive in 16 of 41 MIBG-avid metastatic lesions. After six courses of multidrug chemotherapy, 30 I-131-MIBG-avid neuroblastoma metastases that were Tc-99(m)-MIBI-negative at the time of diagnosis still did not show significant sestamibi accumulation. Follow-up demonstrated that all lesions that were Tc-99(m)-MIBI-avid at the time of diagnosis remained negative. Of these 16 lesions, seven were positive for I-131-MIBG accumulation with no reduction in size, and nine showed resolution after therapy. New metastatic foci detected by MIBG scintigraphy did not accumulate Tc-99(m)-MIBI. Clinical evaluation of patients with no Tc-99(m)-MIBI uptake in primary and secondary sites of neuroblastoma confirmed that they were resistant to multidrug chemotherapy. AII Tc-99(m)-MIBI-positive lesions, irrespective of clinical outcome, demonstrated significant clearance of tracer on the delayed images. We conclude that Tc-99(m)-MIBI has no role in the staging of neuroblastoma. Sestamibi is a well-documented transport substrate for P-glycoprotein-related multidrug resistance and serial imaging may provide prognostic information on the therapeutic value of chemotherapy. ((C) 1999 Lippincott Williams & Wilkins).Öğe The role of Tc-99m MIBI imaging in the assessment of drug resistance in musculo-skeletal tumors.(Springer Verlag, 1999) Burak, Z; Erinc, R; Ozcan, Z; Ersoy, O; Basdemir, G; Dirlik, A; Sabah, D; Moretti, JLÖğe The role of Tc-99m-MIBI scintigraphy in the assessment of MDR1 overexpression in patients with musculoskeletal sarcomas: comparison with therapy response(Springer-Verlag, 2001) Burak, Z; Ersoy, O; Moretti, JL; Erinc, R; Ozcan, Z; Dirlik, A; Sabah, D; Basdemir, GThe 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 (Tc-99m-MIBI) scintigraphy for functional imaging of the MDR1 phenotype in patients with musculoskeletal sarcomas. We aimed to compare Tc-99m-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 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 Patlak-Rutland analysis. Tumour to background (T/B) ratios of both early and delayed 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 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 Tc-99m-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 Tc-99m-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 Tc-99m-MIBI in bone and soft tissue sarcomas did not correlate with Pgp expression. 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 between patients with high and patients with low Pgp expression.Öğe Tc-99m-MIBI imaging as a predictor of therapy response in osteosarcoma compared with multidrug resistance-associated protein and P-glycoprotein expression(Soc Nuclear Medicine Inc, 2003) Burak, Z; Moretti, JL; Ersoy, O; Sanli, U; Kantar, M; Tamgac, F; Basdemir, GIn vitro studies have demonstrated that Tc-99m-methoxyisobutylisonitrile (Tc-99m-MIBI) is a transport substrate of multidrug resistance (MDR)-related proteins. The aim of this clinical study was to evaluate whether Tc-99m-MIBI scintigraphy was a functional imaging tool for in vivo detection of multidrug resistance-associated protein (MRP) expression in osteosarcoma and to investigate the role of MRP and Tc-99m-MIBI imaging to predict the clinical outcome. We also examined whether the scintigraphic parameters would help to distinguish the functional capacity of P-glycoprotein (Pgp) and MRP. Methods: Twenty-four patients with a diagnosis of osteosarcoma were studied before neoadjuvant chemotherapy. Tumor-to-background ratios of both early (10 min) and delayed (1 h) images and the percentage washout rate (WR%) of Tc-99m-MIBI were calculated. Immunohistochemical analysis of MRP and Pgp was performed on biopsy specimens, and the response to preoperative chemotherapy was assessed by histopathologic examination. Results: Fifteen of 24 osteosarcoma samples in our series (62.5%) showed significant expression of MRP. The level of MRP expression was significantly correlated with the WR% of Tc-99m-MIBI (r = 0.58, P = 0.003), and the WR% of Tc-99m-MIBI was significantly faster in patients with high MRP expression than in those with a low MRP score (P = 0.007). The clearance rate of Tc-99m-MIBI was significantly slower in tumor samples with negative or low expression of both Pgp and MRP (16% +/- 6.2%) when compared with osteosarcomas with high expression of both proteins (31.7% +/- 8.7%) (P = 0.001). There was not a significant difference between the WR% of 99mTc-MIBI in tumors with coexpression of both proteins and in tumors with high expression of either Pgp or MRP. Both the rate of MRP expression and the WR% of Tc-99m-MIBI were significantly correlated with response rate. Conclusion: Our results suggest that the WR% of Tc-99m-MIBI is correlated with MRP expression. Both the WR% of Tc-99m-MIBI and MRP expression are correlated with therapy response. Tc-99m-MIBI can be used as a general probe for functional imaging of both Pgp and MRP; however, it is not capable of differentiating the functional status of either MDR-related glycoprotein.Öğe Tc-99m-MIBI imaging as a predictor of therapy response in osteosarcoma compared with multidrug resistance-associated protein and P-glycoprotein expression(Soc Nuclear Medicine Inc, 2003) Burak, Z; Moretti, JL; Ersoy, O; Sanli, U; Kantar, M; Tamgac, F; Basdemir, GIn vitro studies have demonstrated that Tc-99m-methoxyisobutylisonitrile (Tc-99m-MIBI) is a transport substrate of multidrug resistance (MDR)-related proteins. The aim of this clinical study was to evaluate whether Tc-99m-MIBI scintigraphy was a functional imaging tool for in vivo detection of multidrug resistance-associated protein (MRP) expression in osteosarcoma and to investigate the role of MRP and Tc-99m-MIBI imaging to predict the clinical outcome. We also examined whether the scintigraphic parameters would help to distinguish the functional capacity of P-glycoprotein (Pgp) and MRP. Methods: Twenty-four patients with a diagnosis of osteosarcoma were studied before neoadjuvant chemotherapy. Tumor-to-background ratios of both early (10 min) and delayed (1 h) images and the percentage washout rate (WR%) of Tc-99m-MIBI were calculated. Immunohistochemical analysis of MRP and Pgp was performed on biopsy specimens, and the response to preoperative chemotherapy was assessed by histopathologic examination. Results: Fifteen of 24 osteosarcoma samples in our series (62.5%) showed significant expression of MRP. The level of MRP expression was significantly correlated with the WR% of Tc-99m-MIBI (r = 0.58, P = 0.003), and the WR% of Tc-99m-MIBI was significantly faster in patients with high MRP expression than in those with a low MRP score (P = 0.007). The clearance rate of Tc-99m-MIBI was significantly slower in tumor samples with negative or low expression of both Pgp and MRP (16% +/- 6.2%) when compared with osteosarcomas with high expression of both proteins (31.7% +/- 8.7%) (P = 0.001). There was not a significant difference between the WR% of 99mTc-MIBI in tumors with coexpression of both proteins and in tumors with high expression of either Pgp or MRP. Both the rate of MRP expression and the WR% of Tc-99m-MIBI were significantly correlated with response rate. Conclusion: Our results suggest that the WR% of Tc-99m-MIBI is correlated with MRP expression. Both the WR% of Tc-99m-MIBI and MRP expression are correlated with therapy response. Tc-99m-MIBI can be used as a general probe for functional imaging of both Pgp and MRP; however, it is not capable of differentiating the functional status of either MDR-related glycoprotein.Öğe To use MIBI or not to use MIBI? That is the question when assessing tumour cells(Springer, 2005) Moretti, JL; Hauet, N; Caglar, M; Rebillard, O; Burak, ZTc-99m-sestamibi (MIBI) is a well-known tumour imaging agent. Its retention within tumour cell mitochondria is related to perfusion and to the magnitude of the electrical gradient, reflecting cell viability. Several internal cell factors modulate this uptake; for example, multidrug resistance membrane proteins (Pgp and MRP1) and anti-apoptotic BCl-2 protein of the outer mitochondrial membrane can limit retention of MIBI. At the early stage of cell apoptosis, the electrical driving forces of MIBI uptake are impaired, and influx and accumulation are reduced. It seems clear that MIBI can be used before treatment to detect drug resistance, assess anti-apoptotic status and predict treatment efficacy. Although it has been suggested that MIBI might be used to monitor tumour response to treatment, MIBI is unable to differentiate tumours with ongoing apoptosis from those developing drug resistance.
