叶酸-青霉素G酰化酶对SKOV3实体肿瘤靶向性的实验研究

采用Iodogen法对叶酸-青霉素G酰化酶(Folate-conjugated Penicillin G Amidase,F-PGA)和PGA进行125I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125I-F-PGA后4~24 h肿瘤显像较清晰,而注射125I-PGA组所有时相均未见明显的肿瘤部位放射性浓聚影;125I-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=0.014 6),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。

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

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 125I-F-PGA and 125I-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 125I-F-PGA administered group,however which is not seen in the contrast group of 125I-PGA at any time.The radioactivity ratio of tumor to muscle(T/M) of 125I-F-PGA is obviously higher than that of the contrast(F=13.38,P=0.014 6).125I-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.