Preclinical Study of Radioimmunoguided Surgery Using Metastases Model of Human Colon Cancer in Congenitally Athymic mice.

在先天性胸腺发育不全的小鼠中建立了人类结肠癌（HCC）在肝脏、肺和腹膜中可复制的小鼠转移模型，并评估了伽马探测探针（GDP）在使用放射性标记单克隆抗体（mAb）检测肝转移中的效用。小鼠脾内注射HT29LMM肝细胞后100%发生肝转移，腹腔注射HT29LMM肝细胞后100%发生腹膜转移。此外，60%的小鼠在尾静脉注射后发生肺转移。肝转移小鼠静脉注射40 μ Ci/4mugof I-125标记的mAb HT 29-15和同型匹配的对照mAb （BL-3）。非荷瘤对照小鼠注射相同剂量的I-125标记单抗HT29-15。使用GDP，每天测量心脏区域，肝脏区域（右侧）。单抗HT-29-15荷瘤组右侧外壁/心脏比例显著高于对照组。外部测量可以检测到仅重161mg的小肿瘤。在第5天和第7天剖腹探查术中小的孤立性转移。平均转移灶/心脏GDP比值为1.7，肿瘤小至51mg。这些实验结果证实了GDP检测结肠癌小肝转移的有效性，并说明了探针测量放射性标记单抗摄取的重要特征。

Reproducible murine metastases models in the liver, lung, and peritoneum from human colon cancer (HCC) were developed in congenitally athymic mice, and the utility of a gamma detecting probe (GDP) in the detection of hepatic metastases using radiolabeled monoclonal antibody (mAb) was assessed.One hundred percent of mice developed hepatic metastases after intrasplenic injection of HT29LMM HCC cells, and 100% also had peritoneal metastases after intraperitoneal injection. Additionally, 60% of mice developed lung metastases after tail vein injection.Mice with hepatic metastases were injected intravenously with 40 mu Ci/4mugof I-125 labeled mAb HT 29-15 and an isotype-matched control mAb (BL-3). And non-tumor-bearing control mice were injected with the same dose of I-125 labeled mAb HT29-15. Using GDP, measurements were obtained daily over the region of the heart, the region of the liver (the right flank). External right flank/heart ratios were significantly higher in the tumor-bearing group with mAb HT-29-15 than in controls. External measurements allowed detection of small tumors weighing only 161mg. Intraoperative measurements of small isolated metastasis were obtained at laparotomy on days 5 and 7. The mean metastasis/heart GDP ratio count was 1.7, and tumors as small as 51mg in weight could be identified.These experimental results confirm the usefulness of the GDP for the detection of small hepatic metastases from colon cancer, and illustrate important features of probe measurement of radiolabeled mAb uptake.