Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Cancer Biother Radiopharm. 2012 Aug;27(6):353-64. doi: 10.1089/cbr.2012.1184. Epub 2012 Jun 12.
The introduction of the short-lived α-emitter (211)At to intraperitoneal radioimmunotherapy has raised the issue of the tolerance dose of the peritoneum. The short range of the α-particles (70 μm) and the short half-life (7.21 h) of the nuclide yield a dose distribution in which the peritoneum is highly irradiated compared with other normal tissues. To address this issue, mice were injected with (211)At-trastuzumab to irradiate the peritoneum to absorbed doses ranging between 0 and 50 Gy and followed for up to 34 weeks. The peritoneum-to-plasma clearance of a small tracer, (51)Cr-ethylenediamine tetraacetic acid, was measured for evaluation of the small solute transport capacity of the peritoneal membrane. The macroscopic status of the peritoneum and the mesenteric windows was documented when the mice were sacrificed. Biopsies of the peritoneum were taken for morphology and immunohistochemical staining against plasminogen activator inhibitor-1 and calprotectin. Peritoneum-to-plasma clearance measurements indicated a dose-dependent decrease in peritoneal transport capacity in irradiated mice. However, macroscopic and microscopic evaluations of the peritoneal membrane showed no difference between irradiated mice versus controls. The results imply that the peritoneal membrane tolerates absorbed doses as high as 30-50 Gy from α-particle irradiation with limited response.
将短半衰期的 α 发射体 (211)At 引入腹腔内放射免疫治疗引发了对腹膜耐受剂量的关注。α 粒子的短射程（70μm）和核素的短半衰期（7.21h）导致了一种剂量分布，其中与其他正常组织相比，腹膜受到高度照射。为了解决这个问题，将 (211)At-曲妥珠单抗注射到小鼠体内，以将腹膜照射到 0 至 50Gy 的吸收剂量范围内，并进行长达 34 周的随访。通过测量小示踪剂（51）Cr-乙二胺四乙酸的腹膜-血浆清除率来评估腹膜膜的小分子转运能力。当小鼠被处死时，记录腹膜和肠系膜窗的宏观状态。对腹膜进行活检，用于形态学和针对纤溶酶原激活物抑制剂-1 和钙卫蛋白的免疫组织化学染色。腹膜-血浆清除率测量表明，在接受照射的小鼠中，腹膜转运能力呈剂量依赖性下降。然而，对腹膜膜的宏观和微观评估显示，照射小鼠与对照组之间没有差异。这些结果表明，腹膜膜可以耐受高达 30-50Gy 的 α 粒子照射的吸收剂量，而反应有限。
