A Microdosimetry model of kidney for nephrotoxicity due to internal radiation therapy

Introduction: We describe a nephron-based dosimetry model for renal toxicity for radiopharmaceutical therapy suited to the nonuniform activity distribution of radiopharmaceutical. In radiopharmaceutical therapy, renal toxicity is observed while whole-kidney and renal cortex absorbed dose values are below toxicity thresholds established by external beam and targeted radiope ptide therapy. Average dose to a kidney is not a perfect index to quantify the damage due to radiation. Obviously, a damage to a small area of nephron can lead to its dysfunction while the average dose may be lower than the tolerance level. The aim of this study is to estimate the absorbed dose along a typical nephron as an index to predict the possible damages to the nephron.   Materials and Methods: Using Gate/GEANT4 Monte Carlo toolkit an idealized nephron model is created using geometrical and anatomical parameters taken from the literature. These samples also provide the data for volume of occupancy of the different compartments of the nephron in the kidney: glomerulus vs. proximal tubule vs. distal tubule. The selected pharmaceuticals were considered attached to radionuclide of choice (Tc-99m, Y-90, Lu-177, In-111). Radionuclides were distributed in the different components of nephron, Monte Carlo simulations were run, the absorbed doses to the model components (self-absorption and cross-absorption) were calculated. Different physics model in Geant4(Penelope, Livermore and Geant4-DNA) were compared together as an evaluation of the results.   Results: Preliminary results show an absorbed dose to the proximal tubule and glomerular cells approximately 2 times greater than that to the kidney as a whole. This difference in conjunction with the relative biological effect (a factor of about 5) would be consistent with the toxicity observed in the experiments. We observed a strong linear relationship between the results obtained using the condenced-history physics model and those derived using the track-structure. This similarity is verified by previous study in spherical geometry for cellular dosimetry. The agreement between data series was evaluated by Blant-Altman analysis.   Conclusion: The nephron model enables optimal implementation of treatment and is a critical step in understanding nephron toxicity for human translation of radiopharmaceutical therapy