Westrøm Sara, Bønsdorff Tina B, Bruland Øyvind S, Larsen Roy H
Oncoinvent AS, Oslo, Norway; Department of Tumor Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Oncoinvent AS, Oslo, Norway.
Transl Oncol. 2018 Apr;11(2):259-267. doi: 10.1016/j.tranon.2017.12.011. Epub 2018 Jan 28.
Ovarian cancer patients with chemotherapy-resistant residual microscopic disease in the peritoneal cavity have a considerable need for new treatment options. Alpha-emitting radionuclides injected intraperitoneally may be an attractive therapeutic option in this situation as they are highly cytotoxic, while their short range in tissues can spare surrounding radiosensitive organs in the abdomen. Herein we evaluate the therapeutic efficacy of a novel α-emitting compound specifically designed for intracavitary radiation therapy.
The α-emitter Ra was absorbed on calcium carbonate microparticles. Immunodeficient, athymic nude mice with human ovarian cancer cells growing intraperitoneally were treated with different activity levels of Ra-microparticles. Tumor growth, survival, and tolerance of the treatment were assessed. Two tumor models based on the cell lines, ES-2 and SKOV3-luc, with different growth patterns were studied.
In both models, intraperitoneal treatment with Ra-microparticles gave significant antitumor effect with either considerably reduced tumor volume or a survival benefit. An advantageous discovery was that only a few kilobecquerels per mouse were needed to yield therapeutic effects. The treatment was well tolerated up to a dose of 1000 kBq/kg with no signs of acute or subacute toxicity observed.
Intraperitoneal α-therapy with Ra-microparticles demonstrated a significant potential for treatment of peritoneal micrometastases in ovarian carcinoma.
对于腹腔内存在化疗耐药微小残留病灶的卵巢癌患者，迫切需要新的治疗选择。腹腔内注射发射α粒子的放射性核素可能是一种有吸引力的治疗选择，因为它们具有高度细胞毒性，而其在组织中的短射程可以使腹部周围的放射敏感器官免受影响。在此，我们评估一种专门为腔内放射治疗设计的新型发射α粒子化合物的治疗效果。
将发射α粒子的镭吸附在碳酸钙微粒上。用不同活性水平的镭微粒对腹腔内生长人卵巢癌细胞的免疫缺陷无胸腺裸鼠进行治疗。评估肿瘤生长、生存情况以及对治疗的耐受性。研究了基于ES-2和SKOV3-luc两种细胞系、具有不同生长模式的两种肿瘤模型。
在两种模型中，腹腔内给予镭微粒治疗均产生了显著的抗肿瘤效果，肿瘤体积显著减小或生存期延长。一个有利的发现是，每只小鼠仅需几千贝克勒尔就能产生治疗效果。在剂量高达1000 kBq/kg时，治疗耐受性良好，未观察到急性或亚急性毒性迹象。
腹腔内用镭微粒进行α治疗显示出治疗卵巢癌腹膜微转移的巨大潜力。
