RT Journal Article SR Electronic T1 MIRD Pamphlet No. 20: The Effect of Model Assumptions on Kidney Dosimetry and Response—Implications for Radionuclide Therapy JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1884 OP 1899 DO 10.2967/jnumed.108.053173 VO 49 IS 11 A1 Barry W. Wessels A1 Mark W. Konijnenberg A1 Roger G. Dale A1 Hazel B. Breitz A1 Marta Cremonesi A1 Ruby F. Meredith A1 Alan J. Green A1 Lionel G. Bouchet A1 A. Bertrand Brill A1 Wesley E. Bolch A1 George Sgouros A1 Stephen R. Thomas YR 2008 UL http://jnm.snmjournals.org/content/49/11/1884.abstract AB 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. Methods: The multiregion kidney dosimetry model of MIRD pamphlet no. 19 has been used to calculate absorbed dose to regional structures based on preclinical and clinical data. Using the linear quadratic model for radiobiologic response, we computed regionally based surviving fractions for the kidney cortex and medulla in terms of their concentration ratios for several examples of radiopharmaceutical uptake and clearance. We used past experience to illustrate the relationship between absorbed dose and calculated biologically effective dose (BED) with radionuclide-induced nephrotoxicity. Results: Parametric analysis for the examples showed that high dose rates associated with regions of high activity concentration resulted in the greatest decrease in tissue survival. Higher dose rates from short-lived radionuclides or increased localization of radiopharmaceuticals in radiosensitive kidney subregions can potentially lead to greater whole-organ toxicity. This finding is consistent with reports of kidney toxicity associated with early peptide receptor radionuclide therapy and 166Ho-phosphonate clinical investigations. Conclusion: Radionuclide therapy dose–response data, when expressed in terms of biologically effective dose, have been found to be consistent with external-beam experience for predicting kidney toxicity. Model predictions using both the multiregion kidney and linear quadratic models may serve to guide the investigator in planning and optimizing future clinical trials of radionuclide therapy.