Journal
CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS
Volume 27, Issue 6, Pages 353-364Publisher
MARY ANN LIEBERT INC
DOI: 10.1089/cbr.2012.1184
Keywords
At-211; alpha therapy; astatine; intraperitoneal therapy; peritoneum; radioimmunotherapy; radiosensitivity
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Funding
- King Gustav V Jubilee Clinic Cancer Research Foundation
- Swedish Cancer Society
- Swedish Research Council
- Swedish Radiation Safety Authority
- Assar Gabrielsson Foundation
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The introduction of the short-lived alpha-emitter At-211 to intraperitoneal radioimmunotherapy has raised the issue of the tolerance dose of the peritoneum. The short range of the a-particles (70 mu m) 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 At-211-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, Cr-51-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 alpha-particle irradiation with limited response.
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