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

使用先天性无胸腺小鼠结肠癌转移模型进行放射免疫引导手术的临床前研究。

• 批准号: 01480334
• 负责人: SAKURAI Kenji
• 金额: $ 1.86万
• 依托单位: The Jikei University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1989
• 资助国家: 日本
• 起止时间: 1989 至 1990
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-01480334/
• 关键词: Monoclonal antibody; Radioimmunoguided surgery; Colon cancer; Hepatic metastases; Tumor specific antigen; radioimmunoguided surgery

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.

建立了可复制的小鼠肝、肺和腹膜人结肠癌肝、肺和腹膜转移模型，并评价了伽马探测探针(GDP)在应用放射性标记的单抗(MAb)检测肝转移中的作用。此外，60%的小鼠在尾静脉注射后出现肺转移。肝转移小鼠静脉注射40mU CI/4mugI-125标记的单抗HT29-15和一株同型匹配的对照单抗(BL-3)。给非荷瘤对照组小鼠注射相同剂量的I-125标记单抗HT29-15。使用国内生产总值，每天测量心脏区域，肝脏区域(右侧)。携带单抗HT-29-15的荷瘤组右翼/心脏外侧比值显著高于对照组。外部测量可以检测到重量只有161毫克的小肿瘤。分别于术中第5天和第7天在剖腹手术中测量孤立的小转移灶，平均转移/心脏GDP比值为1.7，可识别重量最小51 mg的肿瘤。这些实验结果证实了GDP在结肠癌小肝转移灶检测中的作用，并阐明了放射性标记单抗摄取探针测量的重要特征。

项目成果

吉田和彦: "大腸癌転移に関する最近の話題" 外科. 51. 914-919 (1989)

Kazuhiko Yoshida：“结直肠癌转移的最新主题”Surg. 51. 914-919 (1989)

吉田 和彦: "大腸癌転移に関する最近の話題" 外科. 51. 914-919 (1989)

Kazuhiko Yoshida：“结直肠癌转移的最新主题”Surg. 51. 914-919 (1989)

Kazuhiko Yoshida: "Current topics of hepatic metastases from colon cancer." Geka. 51 (9). 914-919 (1989)

Kazuhiko Yoshida：“结肠癌肝转移的当前主题。”

Kazuhiko Yoshida: "A hepatic metastasis model of human colon cancer in congenitally athymic mice." Jikeikai Medical Journal. 36. 209-217 (1989)

Kazuhiko Yoshida：“先天性无胸腺小鼠的人类结肠癌肝转移模型。”