99m Tc-甲氧基异丁基异腈在人肺癌组织中的摄取与多药耐药基因表达的相关性研究

目的探讨甲氧基异丁基异腈(MIBI)在人肺癌组织中的摄取与多药耐药基因(mdr-1)和多药耐药相关蛋白(MRP)基因表达之间的相关性,用以指导临床化疗. 方法研究对象为27例肺癌患者.18例静脉注入99mTc-MIBI 1 110 MBq,60和120 min后分别作胸部双探头单光子发射型计算机断层显像(SPECT),根据病灶和对侧正常肺组织的计数率比值,计算出99mTc-MIBI在肺癌组织中的早期显像摄取比值、延迟显像摄取比值和储留指数.用逆转录聚合酶链反应技术检测27例患者手术切除标本中mdr-1和MRP基因的表达,表达量以mdr-1或MRP条带与内参照β2-微球蛋白条带的吸光度值之比表示. 结果肺癌患者胸部99mTc-MIBI早期显像的阳性率为83.3%(15/18);阳性者摄取比值为1.99±0.64,其中13例作了延迟显像,经过时间衰变校正后,其99mTc-MIBI摄取比值和储留指数分别为2.06±0.69和-45%～33%.手术切除的肺癌组织中mdr-1和MRP基因表达阳性率分别为22.2%(6/27) 和63.0%(17/27),表达量分别为0.39±0.10和0.23±0.17;癌旁正常肺组织中mdr-1和MRP基因表达的阳性率分别为35.0%(7/20)和45.0%(9/20),表达量分别为0.44±0.14和0.17±0.18.肺癌组织与癌旁正常肺组织比较,mdr-1和MRP基因表达的差异无显著意义.肺癌组织MRP基因表达的阳性率高于mdr-1(P< 0.05).肺癌组织mdr-1和MRP基因共表达量以及MRP基因表达量,与99mTc-MIBI早期显像摄取比值和储留指数之间无明显相关性(P>0.05). 结论肺癌的原发性耐药与mdr-1和MRP基因的表达水平关系不大,可能存在其他耐药机制;用99mTc-MIBI SPECT检测未经化疗的原发性肺癌患者mdr1和MRP基因的表达,临床价值不大.

Correlation of the uptake of technetium-99m methoxyisobutyl isonitrile with expression of multidrug resistance genes mdr-1 and MRP in human lung cancer

OBJECTIVE: To investigate the relationship between the uptake of technetium-99m methoxyisobutyl isonitrile ((99m)Tc-MIBI) and the expression of multidrug resistance genes mdr-1 and MRP in lung cancer so as to guide chemotherapy. METHODS: Eighteen lung cancer patients were given 1 110 MBq(99m)Tc-MIBI intravenously. Chest single-photon emission-computed tomography was performed 60 and 120 min after the injection. The early and delay uptake rates and retain index of (99m)Tc-MIBI were calculated by the count ratio of the lung lesion to contralateral normal lung tissue. The expressions of mdr-1 and MRP genes in specimens of lung cancer and normal lung tissues near the cancers resected during operation among the 27 patients were detected with RT-PCR method. RESULTS: The positive rate of (99m)Tc-MIBI in the chest of lung cancer patients was 83.3% (15/18). The early uptake ratio of imaging in lung cancer patients was 1.99 +/- 0.64. After time decay correction, the rate of target to background and the retain index in 13 delay imagings were 2.06 +/- 0.69 and -45% approximately 33% respectively. In specimens of lung cancer, the positive expression rates of mdr-1 and MRP were 22.2%(6/27) and 63%(17/27) with the expression amount of 0.39 +/- 0.1 and 0.23 +/- 0.17 respectively. In specimens of normal lung tissues near lung cancer, the positive expression rates of mdr-1 and MRP genes were 35%(7/20) and 45.0%(9/20) with the expression amount of 0.44 +/- 0.14 and 0.17 +/- 0.18 respectively. In lung cancer tissues, the positive rate of MRP was higher than that of mdr-1 (P < 0.05), however, in the tissues near lung cancer, no significant difference was found between the positive rate of MRP and that of mdr-1 (P >< 0.05). There was no marked correlation (P >< 0.05) among the co-expression or expression of mdr-1 and/or MRP and the early uptake or retain index in lung cancer. CONCLUSION: The primary chemoresistance of lung cancer has not significant correlation to the expression of multidrug resistance genes mdr-1 and MRP. Other resistance mechanism may exist. (99m)Tc-MIBI imaging has not much clinical value in predicting the expression of mdr-1 and MRP genes.