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Title: Mitigation of radiation nephropathy after internal {alpha}-particle irradiation of kidneys

Purpose: Internal irradiation of kidneys as a consequence of radioimmunotherapy, radiation accidents, or nuclear terrorism can result in radiation nephropathy. We attempted to modify pharmacologically, the functional and morphologic changes in mouse kidneys after injection with the actinium ({sup 225}Ac) nanogenerator, an in vivo generator of {alpha}- and {beta}-particle emitting elements. Methods and Materials: The animals were injected with 0.35 {mu}Ci of the {sup 225}Ac nanogenerator, which delivers a dose of 27.6 Gy to the kidneys. Then, they were randomized to receive captopril (angiotensin-converting enzyme inhibitor), L-158,809 (angiotensin II receptor-1 blocker), spironolactone (aldosterone receptor antagonist), or a placebo. Results: Forty weeks after the {sup 225}Ac injection, the placebo-control mice showed a significant increase in blood urea nitrogen (BUN) (87.6 {+-} 6.9 mg/dL), dilated Bowman spaces, and tubulolysis with basement membrane thickening. Captopril treatment accentuated the functional (BUN 119.0 {+-} 4.0 mg/dL; p <0.01 vs. placebo controls) and histopathologic damage. In contrast, L-158,809 offered moderate protection (BUN 66.6 {+-} 3.9 mg/dL; p = 0.02 vs. placebo controls). Spironolactone treatment, however, significantly prevented the development of histopathologic and functional changes (BUN 31.2 {+-} 2.5 mg/dL; p <0.001 vs. placebo controls). Conclusions: Low-dose spironolactone and, to a lesser extent, angiotensin receptor-1 blockade canmore » offer renal protection in a mouse model of internal {alpha}-particle irradiation.« less
Authors:
 [1] ;  [2] ;  [1] ;  [3] ;  [4] ;  [2] ;  [5]
  1. Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center, New York, NY (United States)
  2. Department of Pathology, Cornell University Weill Medical College, New York, NY (United States)
  3. (United States)
  4. Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD (United States)
  5. Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center, New York, NY (United States) and Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY (United States). E-mail: d-scheinberg@ski.mskcc.org
Publication Date:
OSTI Identifier:
20793437
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 64; Journal Issue: 5; Other Information: DOI: 10.1016/j.ijrobp.2005.11.036; PII: S0360-3016(05)02985-8; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ACTINIUM 225; ALDOSTERONE; ALPHA PARTICLES; ANGIOTENSIN; BLOOD; ENZYME INHIBITORS; IN VIVO; INTERNAL IRRADIATION; KIDNEYS; MICE; RADIATION DOSES; RADIOIMMUNOTHERAPY; RECEPTORS