CAJ | 학술논문

目的研究131 I标记抗人表皮生长因子受体-2蛋白(HER-2/neu)单克隆抗体Herceptin在正常昆明小鼠和荷人卵巢癌裸鼠体内的生物分布及荷人卵巢癌裸鼠的放射免疫显像特点.方法 (1)Iodogen法131I标记Herceptin,测定其标记率、放化纯、稳定性及免疫活性.(2)流式细胞仪和免疫组织化学法分别检测人卵巢癌SKOV-3、HO-8910细胞株及瘤组织HER-2/neu表达情况.(3)计算131I-Herceptin经昆明小鼠尾静脉注射后5,15,30 min和1,2,4,12,24,48,72 h及荷瘤裸鼠尾静脉注射后4,12,24和48h的每克组织百分注射剂量率(%ID/g)和肿瘤/非肿瘤组织放射性(T/NT)比值.(4)行131I-Herceptin荷卵巢癌裸鼠模型显像,观察注射后1,2,4,8,12,24,48,72,96和120h显像情况并确定最佳显像时间.结果 (1)131I-Herceptin标记率为89.8%,放化纯为98.4%,24 h后仍大于80%,标记物免疫活性较好.(2)SKOV-3细胞株HER-2/neu高表达,表达率92.67%;而HO-8910细胞株表达很低,表达率仅9.59%.(3)131I-Herceptin在昆明小鼠体内主要经肝、脾及肾代谢,血液快相半排期为0.27 h,慢相半排期为51.96h.在荷人SKOV-3移植瘤部位,24 h时放射性摄取值达到18.08%ID/g,显著高于其他脏器组织;T/NT比值随时间延长逐渐增高,72 h时肿瘤/脑放射性比值高达27.27.(4)SKOV-3荷瘤裸鼠在尾静脉注射131I-Herceptin后2 h即可见移植瘤放射性浓聚,48 h后与周围组织对比更为明显,至120 h时仍见移植瘤部位放射性明显浓聚,与对侧感兴趣区比值高达11.44.而HO-8910荷瘤裸鼠各时间点移植瘤几乎未见放射性浓聚.结论 131I-Herceptin对荷人SKOV-3移植瘤具有良好的靶向作用,有望用于高表达HER-2/neu的人卵巢癌患者放射免疫显像及其复发转移灶的靶向治疗.
목적 연구131 I표기항인표피생장인자수체-2단백(HER-2/neu)단극륭항체Herceptin재정상곤명소서화하인란소암라서체내적생물분포급하인란소암라서적방사면역현상특점.방법 (1)Iodogen법131I표기Herceptin,측정기표기솔、방화순、은정성급면역활성.(2)류식세포의화면역조직화학법분별검측인란소암SKOV-3、HO-8910세포주급류조직HER-2/neu표체정황.(3)계산131I-Herceptin경곤명소서미정맥주사후5,15,30 min화1,2,4,12,24,48,72 h급하류라서미정맥주사후4,12,24화48h적매극조직백분주사제량솔(%ID/g)화종류/비종류조직방사성(T/NT)비치.(4)행131I-Herceptin하란소암라서모형현상,관찰주사후1,2,4,8,12,24,48,72,96화120h현상정황병학정최가현상시간.결과 (1)131I-Herceptin표기솔위89.8%,방화순위98.4%,24 h후잉대우80%,표기물면역활성교호.(2)SKOV-3세포주HER-2/neu고표체,표체솔92.67%;이HO-8910세포주표체흔저,표체솔부9.59%.(3)131I-Herceptin재곤명소서체내주요경간、비급신대사,혈액쾌상반배기위0.27 h,만상반배기위51.96h.재하인SKOV-3이식류부위,24 h시방사성섭취치체도18.08%ID/g,현저고우기타장기조직;T/NT비치수시간연장축점증고,72 h시종류/뇌방사성비치고체27.27.(4)SKOV-3하류라서재미정맥주사131I-Herceptin후2 h즉가견이식류방사성농취,48 h후여주위조직대비경위명현,지120 h시잉견이식류부위방사성명현농취,여대측감흥취구비치고체11.44.이HO-8910하류라서각시간점이식류궤호미견방사성농취.결론 131I-Herceptin대하인SKOV-3이식류구유량호적파향작용,유망용우고표체HER-2/neu적인란소암환자방사면역현상급기복발전이조적파향치료.
Objective To study the biodistribution of anti-HER-2/neu monoclonal antibody Herceptin labeled by 131I(131I-Herceptin) in healthy KM mice and nude mice bearing human ovarian cancer xenografts and radioimmunoimaging (RII) of the nude xenografts-bearing mice.Methods 131I-Herceptin was prepared using Iodogen method.The labeling efficiency, radiochemical purity, stability and immunocompetence were measured.The percentage activity of injection dose per gram of tissue (%ID/g) and the radioactivity ratio of tumor to non-tumor tissue (T/NT) were calculated for each time point.The optimal time for imaging was investigated by comparing the 131I-Herceptin SPECT for the nude mouse models bearing ovarian cancer xenografts at different time points.Results The labeling efficiency and radiochemical purity of 131I-Herceptin were 89.8% and 98.4%, respectively.The labeling was stable and had good immunocompetence.131 I-Herceptin was cleared rapidly mainly through liver, spleen and kidneys, consistent with first order two-compartment model.The uptake of 131I-Herceptin in the tumors bearing human SKOV-3 xenografts was much higher than that in nontumor tissue.The% ID/g was 18.08 in the tumor at 24 h post injection.The T/NT ratio increased with time and was 27.27 at 72 h post injection.The tumors in nude mice bearing SKOV-3 xenografts could be visualized on 131I-Herceptin SPECT imaging 2 h post injection; definitely identiffed 48 h post injection and the radioactivity ratio of tumor to contralateral tissue was 11.44 at 120 h post injection.However, the tumor in nude mice bearing HO-8910 xenografts did not show abnormal uptake of 131 I-Herceptin at each time point.Conclusions 131 I-Herceptin is a good radiopharmaceutical targeting SK-OV-3 xeuografts and it may be useful in imaging carcinoma of ovary and target therapy of its metastases with high HER-2/neu expression.