Fujiwara Kentaro, Koyama Keitaro, Suga Kosuke, Ikemura Masako, Saito Yasutaka, Hino Akihiro, Iwanari Hiroko, Kusano-Arai Osamu, Mitsui Kenichi, Kasahara Hiroyuki, Fukayama Masashi, Kodama Tatsuhiko, Hamakubo Takao, Momose Toshimitsu
Department of Radiology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
SANKYO LABO SERVICE Co., Ltd., Edogawaku, Tokyo, Japan.
PLoS One. 2015 May 27;10(5):e0125468. doi: 10.1371/journal.pone.0125468. eCollection 2015.
ROBO1 is a membrane protein that contributes to tumor metastasis and angiogenesis. We previously reported that 90Y-labeled anti-ROBO1 monoclonal antibody (90Y-anti-ROBO1 IgG) showed an antitumor effect against ROBO1-positive tumors. In this study, we performed a biodistribution study and radioimmunotherapy (RIT) against ROBO1-positive small cell lung cancer (SCLC) models.
For the biodistribution study, 111In-labeled anti-ROBO1 monoclonal antibody (111In-anti-ROBO1 IgG) was injected into ROBO1-positive SCLC xenograft mice via the tail vein. To evaluate antitumor effects, an RIT study was performed, and SCLC xenograft mice were treated with 90Y-anti-ROBO1 IgG. Tumor volume and body weight were periodically measured throughout the experiments. The tumors and organs of mice were then collected, and a pathological analysis was carried out.
As a result of the biodistribution study, we observed tumor uptake of 111In-anti-ROBO1 IgG. The liver, kidney, spleen, and lung showed comparably high accumulation of 111In-labeled anti-ROBO1. In the RIT study, 90Y-anti-ROBO1 IgG significantly reduced tumor volume compared with baseline. Pathological analyses of tumors revealed coagulation necrosis and fatal degeneration of tumor cells, significant reduction in the number of Ki-67-positive cells, and an increase in the number of apoptotic cells. A transient reduction of hematopoietic cells was observed in the spleen, sternum, and femur.
These results suggest that RIT with 90Y-anti-ROBO1 IgG is a promising treatment for ROBO1-positive SCLC.
ROBO1是一种膜蛋白，在肿瘤转移和血管生成中发挥作用。我们之前报道过，90Y标记的抗ROBO1单克隆抗体（90Y-抗ROBO1 IgG）对ROBO1阳性肿瘤具有抗肿瘤作用。在本研究中，我们针对ROBO1阳性的小细胞肺癌（SCLC）模型进行了生物分布研究和放射免疫治疗（RIT）。
在生物分布研究中，将111In标记的抗ROBO1单克隆抗体（111In-抗ROBO1 IgG）经尾静脉注射到ROBO1阳性的SCLC异种移植小鼠体内。为评估抗肿瘤效果，进行了RIT研究，用90Y-抗ROBO1 IgG治疗SCLC异种移植小鼠。在整个实验过程中定期测量肿瘤体积和体重。然后收集小鼠的肿瘤和器官并进行病理分析。
生物分布研究结果显示，我们观察到111In-抗ROBO1 IgG在肿瘤中的摄取。肝脏、肾脏、脾脏和肺中111In标记的抗ROBO1积累量相对较高。在RIT研究中，与基线相比，90Y-抗ROBO1 IgG显著减小了肿瘤体积。肿瘤的病理分析显示肿瘤细胞出现凝固性坏死和严重变性，Ki-67阳性细胞数量显著减少，凋亡细胞数量增加。在脾脏、胸骨和股骨中观察到造血细胞短暂减少。
这些结果表明，90Y-抗ROBO1 IgG的RIT是治疗ROBO1阳性SCLC的一种有前景的疗法。
