Kim Y S, Cho S W, Lee K J, Hahm K B, Wang H J, Yim H, Jin Y M, Park C H
Department of Gastroenterology, Ajou University, Suwon, Korea.
Clin Nucl Med. 1999 Nov;24(11):874-9. doi: 10.1097/00003072-199911000-00011.
Resistance to chemotherapeutic drugs continues to be one of the major unsolved problems in the treatment of cancer. Multidrug resistance is defined as the ability of cells exposed to a single drug to develop resistance to a broad range of structurally and functionally unrelated drugs as a result of enhanced outward transport of drugs mediated by P-glycoprotein that is encoded by multidrug resistance genes. Recent evidence has shown that Tc-99m MIBI is a suitable transport substrate for P-glycoprotein. A potential advantage of Tc-99m MIBI SPECT is its superiority to diagnose noninvasively the presence of P-glycoprotein overexpression in vivo. In this study, the authors determined the association of enhanced MIBI efflux in Tc-99m MIBI SPECT with overexpression of P-glycoprotein in hepatocellular carcinoma.
Thirty-five patients with hepatocellular carcinoma were enrolled in the study. Tc-99m MIBI SPECT was performed 10 minutes after intravenous injection of 20 mCi Tc-99m MIBI. All patients had liver biopsy or surgery within 1 week of MIBI imaging. Immunohistochemical study of the biopsy or resected hepatocellular carcinoma specimens was performed using the avidin-biotin-peroxidase technique with monoclonal antibody JSB-1 directed against P-glycoprotein.
On Tc-99m MIBI SPECT, 30 of 35 (85.7%) patients with hepatocellular carcinoma had no Tc-99m MIBI uptake in tumor lesions, whereas five patients with hepatocellular carcinoma had Tc-99m MIBI uptake in tumor lesions. P-glycoprotein expression was observed in tumor tissues of all the patients without Tc-99m MIBI uptake, whereas among the five patients with Tc-99m MIBI uptake, no P-glycoprotein expression was seen in tumor lesions (P < 0.015).
Tc-99m MIBI SPECT is useful for noninvasively predicting the presence of MDR1 gene-encoded P-glycoprotein in patients with hepatocellular carcinoma.
对化疗药物的耐药性仍然是癌症治疗中主要未解决的问题之一。多药耐药性被定义为暴露于单一药物的细胞由于由多药耐药基因编码的P-糖蛋白介导的药物外向转运增强,而对多种结构和功能无关的药物产生耐药性的能力。最近的证据表明,锝-99m甲氧基异丁基异腈(Tc-99m MIBI)是P-糖蛋白的合适转运底物。Tc-99m MIBI单光子发射计算机断层扫描(SPECT)的一个潜在优势是其在体内非侵入性诊断P-糖蛋白过表达存在方面的优越性。在本研究中,作者确定了Tc-99m MIBI SPECT中MIBI流出增强与肝细胞癌中P-糖蛋白过表达之间的关联。
35例肝细胞癌患者纳入本研究。静脉注射20毫居里(mCi)Tc-99m MIBI后10分钟进行Tc-99m MIBI SPECT检查。所有患者在MIBI成像后1周内进行肝活检或手术。使用抗P-糖蛋白的单克隆抗体JSB-1,采用抗生物素蛋白-生物素-过氧化物酶技术对活检或切除的肝细胞癌标本进行免疫组织化学研究。
在Tc-99m MIBI SPECT上,35例肝细胞癌患者中有30例(85.7%)肿瘤病灶无Tc-99m MIBI摄取,而5例肝细胞癌患者肿瘤病灶有Tc-99m MIBI摄取。在所有无Tc-99m MIBI摄取的患者肿瘤组织中观察到P-糖蛋白表达,而在5例有Tc-99m MIBI摄取的患者中,肿瘤病灶未见P-糖蛋白表达(P < 0.015)。
Tc-99m MIBI SPECT有助于非侵入性预测肝细胞癌患者中多药耐药基因1(MDR1)编码的P-糖蛋白的存在。