Burak Z, Ersoy O, Moretti J L, Erinç R, Ozcan Z, Dirlik A, Sabah D, Basdemir G
Department of Nuclear Medicine, Ege University Medical Faculty, Bornova, Izmir, Turkey.
Eur J Nucl Med. 2001 Sep;28(9):1341-50. doi: 10.1007/s002590100588.
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.
多药耐药（MDR）的出现部分归因于P-糖蛋白（Pgp）的过度表达，这是恶性肌肉骨骼肿瘤新辅助治疗中的一个主要问题。本研究的目的是探讨锝-99m六甲基丙烯胺肟（99mTc-MIBI）闪烁显像在肌肉骨骼肉瘤患者MDR1表型功能成像中的作用。我们旨在比较99mTc-MIBI摄取和洗脱动力学与Pgp表达及化疗反应。对25例（16例男性和9例女性，年龄在8至65岁之间）患有恶性肌肉骨骼肿瘤的患者进行了研究。注射555 - 740 MBq的99mTc-MIBI后，获取受累区域3分钟的动态血流图像，并在10分钟和1小时采集平面图像。从动态图像中，使用Patlak-Rutland分析获得肿瘤灌注指数（TPI）。计算早期和延迟图像的肿瘤与背景（T/B）比值以及99mTc-MIBI的洗脱率百分比（WR%）。对活检标本进行Pgp的免疫组织化学分析，并根据半定量评分系统将表达程度从0到6分级。新辅助治疗后，通过检查存活细胞比例和检测坏死百分比来评估肿瘤反应。将闪烁显像结果与Pgp状态和治疗反应进行比较。无论Pgp状态如何，所有患者在早期图像中均显示出明显的灌注和99mTc-MIBI摄取。早期和延迟图像的T/B比值与Pgp表达之间无显著相关性。我们观察到WR%与Pgp状态之间存在正相关（r = 0.61，P < 0.01），Pgp高表达患者的99mTc-MIBI洗脱率显著高于Pgp评分低的患者（33% ± 9%对17% ± 9%）。25例患者中有21例确定了治疗反应，21例中只有5例坏死百分比超过90%。在大块肿瘤标本中，未发现Pgp表达率或WR%与坏死百分比有显著相关性。总之，99mTc-MIBI在骨肉瘤和软组织肉瘤中的初始摄取与Pgp表达无关。发现99mTc-MIBI的洗脱率与Pgp评分之间存在关系，Pgp高表达患者和低表达患者之间的WR%存在显著差异。
