^(131)Ⅱ标记肝癌单克隆抗体对裸鼠肝癌移植瘤的实验性导向治疗

^(131)I-labelled anti - hepatoma monoclonal antibodies in targeting therapy of hepatoma xenografts in nude mice

作者用Ⅰ标记抗人肝细胞癌单克隆抗体HAb8 HAb18 IgG及其(ab)_2片段。从尾静脉注入碘标记物,对16只荷肝癌裸鼠(SMMU-LTNM)分4组治疗,其中D组为无关抗体对照组,A,D组为单次给药,注入剂量为7.4×10′Bq,B,C组为多次给药,每5d注射1次,每次剂量为4.4×10′Bq,肿瘤扩增至0.3cm直径时起始治疗,观察疗效21d。每天用卡尺测量其瘤体大小,取横径和竖径的1/2值。经过治疗,2周内有较明显的抑瘤或杀瘤效应。显效(CR)者瘤块可消失(n=5),而对照组(n=4)的瘤块扩增了3-4倍,治疗组(n=12)的自然生存率延长7d以上。

Anti - hepatoma monoclonal antibodies HAb8, 18 IgGs and HAb178 F(ab'), were labelled with 131 I according to Chloraminc T method. Labelling rate and radioactivity were 51% and 9.58 × 104 Bq/×g respectively. After administration of the 131 I- labelled conjugates through mouse tail veins, hcpatoma xenografts were clearly imaged . Localization index was 2.15, 3.09 and 6.99 for HAb8, 18 IgG and HAb18 F (ab') 2 respectively.A total of 16 hepatoma - bearing nude mice (SMMU- LTNM) were divided into 4 groups. When xcnografts reached 0.3 cm in diameter, the treatment was begun by injection of the 131 T - conjugates through mouse tail veins. A single 7.4 × 107 Bq injection (A or D group) or multiple injections (2 or 3 times of 4.4 × 107 Bq each) of B and C group were also studied The multiple injections of IgG or F (ab') 2 were spaced on a 5 - day. After 2 weeks of treatment, obvious inhibitory or killing effects on the xenografts were found In animals showing complete response ( n = 5/12), tumor masses diminished dramatically. In the control group, however, the xenografts grew to the extent that their masses were 3-4 times larger than those of the experimental groups, with difference being significant ( P<0.01).Tumor bearing mice were killed during the period from 14-21 days after treatment. Xenografts as well as other organs were sampled and light microscopically viewed according to routine procedure. The vital organs, such as hearts, livers, spleens, lungs, kidneys, brains and so on, showed no pathological lesions. In hepaVoma xcnografts, some tumor cell membranes were found to be disrupted, with obscure cytoplasmic structure and increased cosmophilia, representing necrotic alterations. In some cases, postnecrotic fibrous proliferation was encountered at the periphery of tumors. All this indicates that specific radiotherapy is practically valuable.