（125/131）I-、（186）Re-、（88/90）Y-或（177）Lu标记的抗癌胚抗原单克隆抗体MN-14在结直肠癌源性小腹膜转移小鼠中的生物分布及治疗效果

Biodistribution and therapeutic efficacy of (125/131)I-, (186)Re-, (88/90)Y-, or (177)Lu-labeled monoclonal antibody MN-14 to carcinoembryonic antigen in mice with small peritoneal metastases of colorectal origin.

作者信息

Koppe Manuel J, Bleichrodt Robert P, Soede Annemieke C, Verhofstad Albert A, Goldenberg David M, Oyen Wim J G, Boerman Otto C

机构信息

Department of Surgery, University Medical Center Nijmegen, Nijmegen, The Netherlands.

出版信息

J Nucl Med. 2004 Jul;45(7):1224-32.

PMID:15235070

Abstract

UNLABELLED

Therapeutic efficacy in radioimmunotherapy depends, among other things, on the choice of the radionuclide. The aim of the present study was to determine the most suitable radionuclide for radioimmunotherapy with monoclonal antibody MN-14 to carcinoembryonic antigen in an experimental model of small peritoneal metastases of colorectal origin.

METHODS

In nude mice with intraperitoneal LS174T tumors (diameter, 1-3 mm), the biodistributions of MN-14 labeled with (131)I ((131)I-MN-14), (186)Re-mercaptoacetyltriglycine ((186)Re-MN-14), and (88)Y-diethylenetriaminepentaacetic acid (DTPA) ((88)Y-MN-14) after intravenous and intraperitoneal administration were determined. Subsequently, the therapeutic efficacies of equally toxic activity doses of (131)I-MN-14 (9.25 MBq per mouse), (186)Re-MN-14 (9.25 MBq per mouse), (90)Y-MN-14 (3.15 MBq per mouse), and MN-14 labeled with (177)Lu-DTPA ((177)Lu-MN-14) (8.33 MBq per mouse) after intraperitoneal administration were determined.

RESULTS

Each of the radioimmunoconjugates preferentially accumulated in tumor nodules, both after intravenous administration and after intraperitoneal administration. Values for clearance from blood were similar for all radioimmunoconjugates. The uptake of (88)Y-MN-14 in the liver and spleen was significantly higher than the uptake of (131)I-MN-14 or (186)Re-MN-14. Maximal uptake values (mean +/- SD) in tumors were 58 +/- 7 percentage injected dose per gram of tissue (%ID/g) for (131)I-MN-14 (24 h after administration), 83 +/- 19 %ID/g for (186)Re-MN-14 (72 h after administration), and 148 +/- 89 %ID/g for (88)Y-MN-14 (192 h after administration). Dosimetric analysis of the biodistribution data estimated that the radiation doses guided to the tumor by intraperitoneally administered (131)I-MN-14, (186)Re-MN-14, (90)Y-MN-14, and (177)Lu-MN-14 were 150, 100, 45, and 200 Gy, respectively. The median survival time of control mice, treated with unlabeled MN-14, was 42 d, whereas the median survival times of mice treated with (131)I-MN-14, (186)Re-MN-14, (90)Y-MN-14, and (177)Lu-MN-14 were 100 d (range, 58-142; P < 0.0001), 72 d (range, 46-84; P = 0.0002), 82 d (range, 46-142; P < 0.0001), and 136 d (range, 56-142; P < 0.0001), respectively. At the completion of the experiment (142 d after tumor cell inoculation), no residual disease was found in 8 of 9 long-term survivors ((131)I, n = 3; (90)Y, n = 1; and (177)Lu, n = 4).

CONCLUSION

The uptake of (88)Y-MN-14 in small peritoneal LS174T xenografts was higher than the uptake of (131)I-MN-14 or (186)Re-MN-14. The present study indicates that (131)I and (177)Lu are the most suitable radionuclides for the radioimmunotherapy of small peritoneal metastases.

摘要

未标记

放射免疫治疗的疗效尤其取决于放射性核素的选择。本研究的目的是在结直肠癌起源的小腹膜转移实验模型中，确定用抗癌胚抗原单克隆抗体MN-14进行放射免疫治疗最合适的放射性核素。

方法

在腹腔内有LS174T肿瘤（直径1-3毫米）的裸鼠中，测定静脉内和腹腔内给药后用（131）I标记的MN-14（（131）I-MN-14）、（186）铼-巯基乙酰三甘氨酸（（186）Re-MN-14）和（88）钇-二乙三胺五乙酸（DTPA）（（88）Y-MN-14）的生物分布。随后，确定腹腔内给药后毒性活性剂量相同的（131）I-MN-14（每只小鼠9.25 MBq）、（186）Re-MN-14（每只小鼠9.25 MBq）、（90）Y-MN-14（每只小鼠3.15 MBq）和用（177）镥-DTPA标记的MN-14（（177）Lu-MN-14）（每只小鼠8.33 MBq）的治疗效果。

结果

静脉内给药和腹腔内给药后，每种放射免疫缀合物都优先在肿瘤结节中蓄积。所有放射免疫缀合物从血液中的清除值相似。（88）Y-MN-14在肝脏和脾脏中的摄取明显高于（131）I-MN-14或（186）Re-MN-14。肿瘤中的最大摄取值（平均值±标准差），（131）I-MN-14为58±7注射剂量百分比每克组织（%ID/g）（给药后24小时），（186）Re-MN-14为83±19 %ID/g（给药后72小时），（88）Y-MN-14为148±89 %ID/g（给药后192小时）。生物分布数据的剂量学分析估计，腹腔内给药的（131）I-MN-14、（186）Re-MN-14、（90）Y-MN-14和（177）Lu-MN-14导向肿瘤的辐射剂量分别为150、100、