~(125)I标记美妥昔单抗在不同肿瘤模型中的显像研究
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摘要
目的:该研究旨在评估针对CD147的美妥昔单抗靶向结合其他肿瘤的能力。方法:在人肿瘤细胞系的BALB/c裸小鼠转移瘤模型中,以~(125)I标记美妥昔单抗HAb18F(ab’)2,利用小动物SPECT/CT显像长时间持续观察HAb18F(ab’)2靶向结合人肝癌SMMC-7721、胰腺癌SW1990和肺癌A549细胞的能力,并利用仪器自带的InVivo Scope软件计算肿瘤/肌肉(tumorto-muslce,T/M),比较不同肿瘤摄取~(125)I-HAb18F(ab’)2的能力。结果:SPECT/CT显像结果表明,SMMC-7721、SW1990和A549细胞均高度摄取~(125)I-HAb18F(ab’)2,呈现明显的肿瘤放射性浓集,全身放射性本底低,影像对比度高,T/M比值分别达432、234和26。其中,SW1990与SMMC-7721一样持续摄取长达9 d以上。结论:3种不同类型的肿瘤细胞均能高度摄取美妥昔单抗,并且在肿瘤中滞留时间较长。美妥昔单抗不仅可以用于肝癌,也可试用于肺癌、胰腺癌等其他肿瘤的诊断和治疗。
Objective: The aim of this study was to evaluate the targeting ability of metuximab against other tumors. Methods: HAb18 F(ab')2 was labeled with ~(125)I, and Nano-SPECT/CT was used to observe the targeting effect of HAb18 F(ab')2 on human hepatocellular carcinoma cell line SMMC-7721, pancreatic carcinoma cell line SW1990 and lung cancer cell line A549 continuously. The tumor-to-muscle(T/M) ratio was further calculated with InVivo Scope software. The uptake of ~(125)I-HAb18 F(ab')2 by different tumors was compared. Results: SPECT/CT imaging showed that human cancer cell line SMMC-7721, SW1990 and A549 all displayed high uptake of ~(125)I-HAb18 F(ab')2. The obvious tumor radioactivity concentration and low radioactivity background of whole body made the high image contrast. The T/M ratio in SMMC-7721, SW1990 and A549 was 432, 234 and 26, respectively. The retention of ~(125)I-HAb18 F(ab')2 in SW1990 and SMMC-7221 was both as long as 9 d. Conclusion: All three types of tumors display high uptake of HAb18 F(ab')2, and HAb18 F(ab')2 is able to be detained long in the three tumors. HAb18 F(ab')2 showes the potential to be further applied in the diagnosis and treatment of other tumors besides the liver cancer.
Objective: The aim of this study was to evaluate the targeting ability of metuximab against other tumors. Methods: HAb18 F(ab')2 was labeled with ~(125)I, and Nano-SPECT/CT was used to observe the targeting effect of HAb18 F(ab')2 on human hepatocellular carcinoma cell line SMMC-7721, pancreatic carcinoma cell line SW1990 and lung cancer cell line A549 continuously. The tumor-to-muscle(T/M) ratio was further calculated with InVivo Scope software. The uptake of ~(125)I-HAb18 F(ab')2 by different tumors was compared. Results: SPECT/CT imaging showed that human cancer cell line SMMC-7721, SW1990 and A549 all displayed high uptake of ~(125)I-HAb18 F(ab')2. The obvious tumor radioactivity concentration and low radioactivity background of whole body made the high image contrast. The T/M ratio in SMMC-7721, SW1990 and A549 was 432, 234 and 26, respectively. The retention of ~(125)I-HAb18 F(ab')2 in SW1990 and SMMC-7221 was both as long as 9 d. Conclusion: All three types of tumors display high uptake of HAb18 F(ab')2, and HAb18 F(ab')2 is able to be detained long in the three tumors. HAb18 F(ab')2 showes the potential to be further applied in the diagnosis and treatment of other tumors besides the liver cancer.
引文
[1]LIAN C,GUO Y,ZHANG J,et al.Targeting CD147 is a novel strategy for antitumor therapy[J].Curr Pharm Des,2017,23(29):4410-4421.
[2]XIN X,ZENG X,GU H,et al.CD147/EMMPRIN overexpression and prognosis in cancer:a systematic review and Meta-analysis[J].Sci Rep,2016,6:32804.
[3]刘畅,杜华,卢武胜.131I美妥昔单抗治疗肝癌的研究进展[J].介入放射学杂志,2017,26(1):82-86.
[4]ZHU Z X,LIAO M H,WANG X X,et al.Transcatheter arterial chemoembolization plus 131I-labelled metuximab versus transcatheter arterial chemoembolization alone in intermediate/advanced stage hepatocellular carcinoma:a systematic review and Meta-analysis[J].Korean J Radiol,2016,17(6):882-892.
[5]姚征,陈玉堂,罗君,等。131I美妥昔单抗注射液联合TACE治疗76例中晚期原发性肝癌的疗效及安全性研究[J].介入放射学杂志,2016,25(1):65-69.
[6]边惠洁,陈志南,何凤昌.1 3 1I标记肝癌单克隆抗体HAb18F(ab')2的NBS法的研究[J].细胞与分子免疫学杂志,1996,12(2):28-30.
[7]封兰兰,朱少君,张阳,等.HAb18G/CD147在多种恶性肿瘤中的表达及其临床意义[J].细胞与分子免疫学杂志,2013,29(9):958-961.
[8]GRASS G D,TOOLE B P.How,with whom and when:an overview of CD147-mediated regulatory networks influencing matrix metalloproteinase activity[J].Biosci Rep,2015,36(1):e00283.
[9]LIU M,TSANG J Y S,LEE M,et al.CD147 expression is associated with poor overall survival in chemotherapy treated triple-negative breast cancer[J].J Clin Pathol,2018.[Epub ahead of print].
[10]冯强,米力,边惠洁,等.131I-肝癌单抗片段HAb18F(ab')2注射液药盒的制备[J].同位素,2002,15(3):137-140.
[11]BOSWELL C A,MARIK J,ELOWSON M J,et al.Enhanced tumor retention of a radiohalogen label for site-specific modification of antibodies[J].J Med Chem,2013,56(23):9418-9426.
[2]XIN X,ZENG X,GU H,et al.CD147/EMMPRIN overexpression and prognosis in cancer:a systematic review and Meta-analysis[J].Sci Rep,2016,6:32804.
[3]刘畅,杜华,卢武胜.131I美妥昔单抗治疗肝癌的研究进展[J].介入放射学杂志,2017,26(1):82-86.
[4]ZHU Z X,LIAO M H,WANG X X,et al.Transcatheter arterial chemoembolization plus 131I-labelled metuximab versus transcatheter arterial chemoembolization alone in intermediate/advanced stage hepatocellular carcinoma:a systematic review and Meta-analysis[J].Korean J Radiol,2016,17(6):882-892.
[5]姚征,陈玉堂,罗君,等。131I美妥昔单抗注射液联合TACE治疗76例中晚期原发性肝癌的疗效及安全性研究[J].介入放射学杂志,2016,25(1):65-69.
[6]边惠洁,陈志南,何凤昌.1 3 1I标记肝癌单克隆抗体HAb18F(ab')2的NBS法的研究[J].细胞与分子免疫学杂志,1996,12(2):28-30.
[7]封兰兰,朱少君,张阳,等.HAb18G/CD147在多种恶性肿瘤中的表达及其临床意义[J].细胞与分子免疫学杂志,2013,29(9):958-961.
[8]GRASS G D,TOOLE B P.How,with whom and when:an overview of CD147-mediated regulatory networks influencing matrix metalloproteinase activity[J].Biosci Rep,2015,36(1):e00283.
[9]LIU M,TSANG J Y S,LEE M,et al.CD147 expression is associated with poor overall survival in chemotherapy treated triple-negative breast cancer[J].J Clin Pathol,2018.[Epub ahead of print].
[10]冯强,米力,边惠洁,等.131I-肝癌单抗片段HAb18F(ab')2注射液药盒的制备[J].同位素,2002,15(3):137-140.
[11]BOSWELL C A,MARIK J,ELOWSON M J,et al.Enhanced tumor retention of a radiohalogen label for site-specific modification of antibodies[J].J Med Chem,2013,56(23):9418-9426.