Elgqvist Jorgen, Ahlberg Daniel, Andersson Hakan, Jensen Holger, Johansson Bengt R, Kahu Helena, Olsson Marita, Lindegren Sture
Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
Mathematical Sciences, University of Gothenburg and Chalmers University of Technology, Sweden.
World J Oncol. 2010 Jun;1(3):101-110. doi: 10.4021/wjon2010.05.208w. Epub 2010 May 19.
The aim of this study was to investigate the therapeutic efficacy of advanced ovarian cancer in mice, using α-radioimmunotherapy with different high specific activities. The study was performed using the monoclonal antibody (mAb) MX35 F(ab')2 labeled with the α-particle emitter At.
Animals were intraperitoneally inoculated with ≥1 × 10 cells of the ovarian cancer cell line NIH:OVCAR-3. Four weeks later 9 groups of animals were given 25, 50, or 400 kBq At-MX35 F(ab')2 with specific activities equal to 1/80, 1/500, or 1/1200 (At atom/number of mAbs) for every activity level respectively ( = 10 in each group). As controls, animals were given PBS or unlabeled MX35 F(ab')2 in PBS ( = 10 in each group). Eight weeks after treatment the animals were sacrificed and the presence of macroscopic tumors was determined by meticulous ocular examination of the abdominal cavity. Cumulated activity and absorbed dose calculations on tumor cells and tumors were performed using in house developed program. Specimens for scanning electron-microscopy analysis were collected from the peritoneum at the time of dissection.
Summing over the different activity levels (25, 50, and 400 kBq At-MX35 F(ab')2) the number of animals with macroscopic tumors was 13, 17, and 22 ( = 30 for each group) for the specific activities equal to 1/80, 1/500, or 1/1200, respectively. Logistic-regression analysis showed a significant trend that higher specific activity means less probability for macroscopic tumors ( = 0.02).
Increasing the specific activity indicates a way to enhance the therapeutic outcome of advanced ovarian cancer, regarding macroscopic tumors. Further studies of the role of the specific activity are therefore justified.
本研究旨在使用具有不同高比活度的α放射免疫疗法，研究其对小鼠晚期卵巢癌的治疗效果。该研究使用用α粒子发射体砹标记的单克隆抗体（mAb）MX35 F(ab')2进行。
给动物腹腔内接种≥1×10个卵巢癌细胞系NIH:OVCAR-3细胞。4周后，9组动物分别给予25、50或400 kBq的砹-MX35 F(ab')2，每种活度水平的比活度分别等于1/80、1/500或1/1200（砹原子/单克隆抗体数量）（每组n = 10）。作为对照，给动物注射PBS或PBS中的未标记MX35 F(ab')2（每组n = 10）。治疗8周后，处死动物，通过仔细肉眼检查腹腔来确定肉眼可见肿瘤的存在。使用内部开发的程序对肿瘤细胞和肿瘤进行累积活度和吸收剂量计算。在解剖时从腹膜收集用于扫描电子显微镜分析的标本。
汇总不同活度水平（25、50和400 kBq砹-MX35 F(ab')2），比活度等于1/80、1/500或1/1200时，有肉眼可见肿瘤的动物数量分别为13、17和22只（每组n = 30）。逻辑回归分析显示出显著趋势，即比活度越高，出现肉眼可见肿瘤的概率越低（P = 0.02）。
就肉眼可见肿瘤而言，提高比活度表明是增强晚期卵巢癌治疗效果的一种方法。因此，有必要对比活度的作用进行进一步研究。
