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Renal toxicity associated with small-molecule radionuclide therapy has been shown to be dose-limiting for many clinical studies. Strategies for maximizing dose to the target tissues while sparing normal critical organs based on absorbed dose and biologic response parameters are commonly used in external-beam therapy. However, radiopharmaceuticals passing though the kidneys result in a differential dose rate to suborgan elements, presenting a significant challenge in assessing an accurate dose-response relationship that is predictive of toxicity in future patients. We have modeled the multiregional internal dosimetry of the kidneys combined with the biologic response parameters based on experience with brachytherapy and external-beam radiation therapy to provide an approach for predicting radiation toxicity to the kidneys.

MIRD Pamphlet No. 20: The Effect of Model Assumptions on Kidney Dosimetry and Response—Implications for Radionuclide Therapy