Glomerular Filtration Rate After Alpha-Radioimmunotherapy with 211At-MX35-F(ab′)2: A Long-Term Study of Renal Function in Nude Mice
Publication: Cancer Biotherapy and Radiopharmaceuticals
Volume 24, Issue Number 6
Abstract
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 (α-RIT) with the alpha-particle emitter, 211At, 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 51Cr-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 α-RIT with 211At-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 α-RIT when using 211At-MX35-F(ab′)2.
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Information & Authors
Information
Published In
Cancer Biotherapy and Radiopharmaceuticals
Volume 24 • Issue Number 6 • December 2009
Pages: 649 - 658
PubMed: 20025544
Copyright
Copyright 2009, Mary Ann Liebert, Inc.
History
Published online: 21 December 2009
Published in print: December 2009
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Disclosure Statement
No competing financial interests exist.
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