卵巢癌预定位放射免疫显像的实验研究

The preliminary clinical study of pretargeted radio immunoimaging in ovarian carcinoma

目的：提高放射免疫显像（ｒａｄｉｏｉｍｍｕｎｏｉｍａｇｉｎｇ，ＲＩＩ）质量，建立卵巢癌预定位放射显像技术。方法：将合成的环二乙基三胺五乙酸（ｃｙｃｌｉｃｄｉｅｔｈｙｌｅｎｅｔｒｉａｍｉｎｅｐｅｎｔａａｃｅｔｉｃａｃｉｄ，ｃＤＴＰＡ）与卵巢癌单抗ＣＯＣ１８３Ｂ２进行偶联，Ｓｅｐｈａｄｅｘ分离纯化后，采用免疫组织化学染色及细胞放射自显影对偶联物进行活性测定。将偶联的ＣＯＣ１８３Ｂ２ｃＤＴＰＡ或ＩｇＧ分别经腹腔注入荷人卵巢癌裸鼠腹水瘤模型体内，４８ｈ后，将还原９９ｍＴｃ淋洗液经腹腔注入体内，６ｈ后进行ＲＩＩ。显像后，体外称重并测量瘤及其他正常组织放射性活性，计算瘤与非瘤放射性比值（Ｔ／ＮＴ）。结果：（１）ＣＯＣ１８３Ｂ２ｃＤＴＰＡ与浆液性卵巢癌组织免疫组化染色呈阳性；细胞放射自显影结果可见卵巢癌ＳＫＯＶ３细胞膜周围呈环状显影，提示偶联后单抗仍保留了较好的免疫活性。（２）注射还原９９ｍＴｃ６ｈ后ＲＩＩ，可见实验组荷瘤裸鼠腹腔有特异放射性聚集；而对照荷瘤裸鼠腹腔无特异放射性聚集。实验组各器官Ｔ／ＮＴ值高于对照组，两者差异有显著性（Ｐ＜０．０５）。结论：ｃＤＴＰＡ偶联ＣＯＣ１８３Ｂ２单抗进行卵巢癌预定位放射免疫显像?

Objective: To establish the pretargeted radioimmunoimaging(RII) technique for improving the quality of RII in ovarian carcinoma. Methods: Monoclonal antibody COC183B 2 was conjugated with cyclic DTPA (cyclic diethylenetriamine pentaacetic acid) DTPA anhydride and its immunoactivity was measured by PAP staining or autoradiography in vitro . COC183B 2 cDTPA or normal mouse IgG (NMIgG) were respectively injected intraperitoneally (i.p.) into two groups of nude mice bearing human ovarian carcinoma with ascites.48 hours later, reduced 99m Tc was injected i.p. again. RII was performed 6 hours later. After RII, the γ counting of related tissues was measured to calculate the ratio of radioactivity for tumor and non tumor (T/NT). Results: (1) The coupled COC183B 2 showed good immunoactivity by PAP staining and autoradiography. (2) 6 hours after 99m Tc administration, RII showed clear localization of tumor and T/NT ratios were significantly higher than those of the control group. Conclusion: Monoclonal antibody COC183B 2 coupled by cDTPA used for pretargeted RII is practical, hopefully to be used clinically in ovarian carcinoma.