叶酸-青霉素G酰化酶对SKOV3实体肿瘤靶向性的实验研究  

Experimental Study on the Targeting Ability of Folate-conjugated Penicillin G Amidase to SKOV3 Solid Tumors

作　　者：杨科亚[1] 傅深[1] 范我[2] 张友九[2] 许玉杰[2] 朱然[2] 王道锦[2] 胡明江[2] 张奇[3] 项光亚[3] 

机构地区：[1]上海交通大学附属第六人民医院肿瘤放疗科,上海200233 [2]苏州大学放射医学与公共卫生学院,江苏苏州215123 [3]华中科技大学同济医学院,湖北武汉430030

出　　处：《同位素》2007年第4期209-213,共5页Journal of Isotopes

基　　金：国家自然科学基金资助项目(30300430)

摘　　要：采用Iodogen法对叶酸-青霉索G酰化酶（Folate—conjugated Penicillin G Amidase，F-PGA）和PGA进行^135I标记。将纯化后的标记物由尾静脉注入荷SKOV3实体瘤裸鼠体内，观察F-PGA对叶酸受体阳性的SKOV3的靶向性。结果显示：标记产品纯化后放化纯度〉95％，且体内外稳定性较好；荷SKOV3肿瘤的裸鼠注射^135I-F-PGA后4～24h肿瘤显像较清晰，而注射^135I-PGA组所有时相均未见明显的肿瘤部位放射性浓聚影；^135I-F-PGA组的肿瘤与健侧肌肉的摄取比值（T／M）明显高于对照组（F=13．38，P=0．0146），且在非靶组织中清除较快。表明F-PGA在荷瘤鼠体内能特异性地与叶酸受体阳性的SKOV3实体肿瘤进行靶向结合，其T／NT〉1，有望用于靶向治疗。By isotope tracer technique, experiments of SPECT and biodistribution on nude mice bearing tumor are performed to explore whether folate-conjugated penicillin G amidase （F-PGA） has the ability of targeting to folate receptor positive solid tumors, which will be helpful to establish a base for further targeting therapies. The results showed that the labeling efficiencies of ^135I-F-PGA and ^135I-PGA are 90%, and their radiochemical purities are more than 95% after purified, with suitable stabilities both in vivo and in vitro. At 4-24 h postinjection, the appreciable radioactivity accumulation at tumor position can be obtained from SPECT images of ^135I-F-PGA administered group, however which is not seen in the contrast group of ^135I-PGA at any time. The radioactivity ratio of tumor to muscle （T/M） of ^135I-F-PGA is obviously higher than that of the contrast（F=13.38, P=0. 014 6）. ^135I-F- PGA is quickly cleared from non-targeted sites. It indicated that by folate receptor pathway, F-PGA can specially target to folate receptor positive SKOV3 solid tumors in vivo, with good feature of target to non-target tissues, and it may be an ideal agent for targeting therapies.

关 键 词：^135I 叶酸-青霉索G酰化酶(F-PGA) 叶酸受体 靶向性 

分 类 号：R817-33[医药卫生—影像医学与核医学] R730.5[医药卫生—放射医学]