Shih Chuen-Ming, Hsu Wu-Huei, Huang Wen-Tao, Wang Jhi-Joung, Ho Shung-Tai, Kao Albert
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
Cancer Lett. 2003 Sep 10;199(1):99-105. doi: 10.1016/s0304-3835(03)00335-5.
In vitro studies have shown that technetium-99m methoxyisobutylisonitrile (Tc-99m MIBI) is a transport substrate for the P-glycoprotein (Pgp) pump. Therefore, Tc-99m MIBI uptake of tumors can be used to predict chemotherapy response in lung cancers. However, whether lung resistance-related protein (LRP) expression affects tumor accumulation and efflux of Tc-99m MIBI in lung cancers is not known. Our aim was to use Tc-99m MIBI uptake of tumors to predict Taxol based chemotherapy response of advanced non-small cell lung cancer (NSCLC) and to compare Pgp or LRP expression. Before chemotherapy with Taxol, 30 patients with stage IIIb or IV NSCLC were enrolled in this study. Chemotherapy response was evaluated in the third month after completion of treatment by clinical and radiological methods. No significant differences were found for other prognostic factors (age, sex, body weight loss, performance status, tumor cell type, and tumor stage) between the 15 patients with good response and the other 15 patients with poor response. Early chest single photon emission computed tomography (SPECT) was performed 10 min after intravenous injection of Tc-99m MIBI. Early tumor-to-normal lung (T/L) uptake ratios were calculated quantitatively on Tc-99m MIBI chest SPECT images. Immunohistochemical analyses were performed on multiple nonconsecutive sections of the biopsy specimens to determine Pgp and LRP expressions. The T/L uptake ratios on early Tc-99m MIBI chest SPECT images of 15 patients with good response were significantly higher than those of the other 15 patients with poor response. Significantly higher T/L uptake ratios were found in patients with negative than positive Pgp expression (p<0.05). However, no significant differences of T/L uptake ratios were found between patients with negative and positive LRP expressions (p>0.05). We concluded that Tc-99m MIBI chest SPECT could accurately predict Taxol base chemotherapy response of patients with advanced NSCLC. In addition, The Tc-99m MIBI tumor uptake was related to Pgp but not LPR expression in NSCLC.
体外研究表明,锝-99m甲氧基异丁基异腈(Tc-99m MIBI)是P-糖蛋白(Pgp)泵的转运底物。因此,Tc-99m MIBI在肿瘤中的摄取可用于预测肺癌的化疗反应。然而,肺癌中肺耐药相关蛋白(LRP)的表达是否会影响Tc-99m MIBI在肿瘤中的摄取和流出尚不清楚。我们的目的是利用肿瘤对Tc-99m MIBI的摄取来预测晚期非小细胞肺癌(NSCLC)基于紫杉醇的化疗反应,并比较Pgp或LRP的表达。在使用紫杉醇化疗前,30例Ⅲb期或Ⅳ期NSCLC患者被纳入本研究。在治疗完成后的第三个月,通过临床和影像学方法评估化疗反应。在15例反应良好的患者和其他15例反应较差的患者之间,未发现其他预后因素(年龄、性别、体重减轻、体能状态、肿瘤细胞类型和肿瘤分期)有显著差异。在静脉注射Tc-99m MIBI后10分钟进行早期胸部单光子发射计算机断层扫描(SPECT)。在Tc-99m MIBI胸部SPECT图像上定量计算早期肿瘤与正常肺组织(T/L)摄取比值。对活检标本的多个非连续切片进行免疫组织化学分析,以确定Pgp和LRP的表达。15例反应良好的患者早期Tc-99m MIBI胸部SPECT图像上的T/L摄取比值显著高于其他15例反应较差的患者。Pgp表达阴性的患者T/L摄取比值显著高于阳性患者(p<0.05)。然而,LRP表达阴性和阳性的患者之间T/L摄取比值无显著差异(p>0.05)。我们得出结论,Tc-99m MIBI胸部SPECT可以准确预测晚期NSCLC患者基于紫杉醇的化疗反应。此外,在NSCLC中,Tc-99m MIBI在肿瘤中的摄取与Pgp有关,而与LPR表达无关。