Department of Radiation Physics, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Cancer Biother Radiopharm. 2009 Dec;24(6):649-58. doi: 10.1089/cbr.2009.0628.
Besides bone marrow, the kidneys are often dose-limiting organs in internal radiotherapy. The effects of high-linear energy transfer (LET) radiation on the kidneys after alpha-radioimmunotherapy (alpha-RIT) with the alpha-particle emitter, (211)At, were studied in nude mice by serial measurements of the glomerular filtration rate (GFR). The renal toxicity was evaluated at levels close to the dose limit for the bone marrow and well within the range for therapeutic efficacy on tumors. Astatinated MX35-F(ab')(2) monoclonal antibodies were administered intravenously to nude mice. Both non-tumor-bearing animals and animals bearing subcutaneous xenografts of the human ovarian cancer cell line, OVCAR-3, were used. The animals received approximately 0.4, 0.8, or 1.2 MBq in one, two, or three fractions. The mean absorbed doses to the kidneys ranged from 1.5 to 15 Gy. The renal function was studied by serial GFR measurements, using plasma clearance of (51)Cr-EDTA, up to 67 weeks after the first astatine injection. A dose-dependent effect on GFR was found and at the time interval 8-30 weeks after the first administration of astatine, the absorbed doses causing a 50% decrease in GFR were 16.4 +/- 3.3 and 14.0 +/- 4.1 Gy (mean +/- SEM), tumor- and non-tumor-bearing animals, respectively. The reduction in GFR progressed with time, and at the later time interval, (31-67 weeks) the corresponding absorbed doses were 7.5 +/- 2.4 and 11.3 +/- 2.3 Gy, respectively, suggesting that the effects of radiation on the kidneys were manifested late. Examination of the kidney sections showed histologic changes that were overall subdued. Following alpha-RIT with (211)At-MX35-F(ab')(2) at levels close to the dose limit of severe myelotoxicity, the effects found on renal function were relatively small, with only minor to moderate reductions in GFR. These results suggest that a mean absorbed dose to the kidneys of approximately 10 Gy is acceptable, and that the kidneys would not be the primary dose-limiting organ in systemic alpha-RIT when using (211)At-MX35-F(ab')(2).
除骨髓外，肾脏通常也是内放射治疗的剂量限制器官。用α-发射体（211）At 进行α-放射免疫治疗（α-RIT）后，高线性能量转移（LET）辐射对肾脏的影响，通过连续测量肾小球滤过率（GFR），在裸鼠中进行了研究。用（211）At-MX35-F（ab'）（2）标记的单克隆抗体通过静脉内给予裸鼠。使用了无肿瘤裸鼠和皮下异种移植人类卵巢癌细胞系 OVCAR-3 的动物。动物接受了约 0.4、0.8 或 1.2MBq 的单次、两次或三次给药。肾脏的平均吸收剂量范围为 1.5 至 15Gy。通过使用血浆清除率（51）Cr-EDTA 进行连续 GFR 测量，在第一次注入锕后 67 周内研究肾功能。发现 GFR 存在剂量依赖性效应，并且在第一次给予锕后 8-30 周的时间间隔内，引起 GFR 降低 50%的吸收剂量分别为 16.4±3.3 和 14.0±4.1Gy（平均值±SEM），分别在肿瘤和非肿瘤动物中。GFR 的降低随时间进展，在后期时间间隔（31-67 周），相应的吸收剂量分别为 7.5±2.4 和 11.3±2.3Gy，表明辐射对肾脏的影响表现较晚。对肾脏切片的检查显示总体上较弱的组织学变化。在用（211）At-MX35-F（ab'）（2）进行接近严重骨髓毒性剂量限制的α-RIT 后，发现对肾功能的影响相对较小，GFR 仅有轻微至中度降低。这些结果表明，肾脏的平均吸收剂量约为 10Gy 是可以接受的，并且在用（211）At-MX35-F（ab'）（2）进行全身α-RIT 时，肾脏不会成为主要的全身α-RIT 剂量限制器官。
