Nonuniform absorbed dose distribution in the kidney: the influence of organ architecture.

The development of novel, systemically administered radionuclide therapies (such as radioimmunotherapy) relies on the ability to predict dose-limiting toxicity to normal tissue. Where the kidney is the principal route of excretion of the radionuclide preparation and/or breakdown of products, nephrotoxicity may be the dose-limiting factor. Until recently, conventional (MIRD) dosimetry assumed the distribution in the kidney to be uniform. A new MIRD phantom of the kidney models it as a set of uniform suborgans. In the work described here, the assumption of uniformity of distribution and of heterogeneity of dose rate (and, thus, absorbed dose) was tested in the mouse model. In this paper, we examine the nonuniformity of distribution and the subsequent dose rate for 4 antibody preparations (IgG (150 kD), F(ab)'2 (100 kD), Fab (50 kD) and sFv (27 kD)) labeled with 4 radionuclides (125I, 131I, 186Re, and 90Y) of interest in radioimmunotherapy (RIT). The kidney was considered as a whole and as two suborgans (cor...