Relevance of external beam dose-response relationships to kidney toxicity associated with radionuclide therapy.

The importance of the kidney as a dose-limiting organ is likely to increase as smaller molecular vectors and radiometals become more commonly used in targeted radionuclide therapy. Data derived from kidney irradiation by external-beam therapy (XRT) indicate that the kidney is radiosensitive. The features of radiation nephropathy seen post-treatment appear similar between local XRT, total-body irradiation (TBI), and radionuclide therapy. For uniform kidney irradiation, tolerance doses appear to be approximately 15-17 Gy in 2 Gy fractions for local XRT and probably less than this (approximately 12 Gy in 2 Gy fractions) when radiation is delivered systemically as TBI in the context of bone marrow transplant protocols. Animal studies indicate that the linear quadratic (LQ) model with an alpha/beta parameter of 1.5-3 Gy seems to adequately describe the XRT fractionation sensitivity of kidney for doses per fraction down to approximately 1 Gy, but may underestimate the effectiveness of fraction sizes less than this. Animal studies have also clarified the dose-dependency of the time to expression of radiation nephropathy and have indicated that radiation nephropathy may be alleviated by pharmacological means.