A MOUSE MODEL FOR CALCULATING CROSS-ORGAN BETA-DOSES FROM YTTRIUM-90-LABELED IMMUNOCONJUGATES

Background. The organs of laboratory mice used in radioimmunotherapy e xperiments are relatively small compared to the ranges of high-energy yttrium-90 (Y-90) beta particles. Current Medical Internal Radiation D ose (MIRD) dosimetry methods do not account for beta energy that escap es an organ. A dosimetry model was developed to provide more realistic dose estimates for organs in mice who received Y-90-labeled antibodie s by accounting for physical and geometric factors, loss of beta dose due to small organ sizes, and cross-organ doses. Methods. The dimensio ns, masses, surface areas, and overlapping areas of different organs o f 10 athymic nude mice, each weighing approximately 25 g, were measure d to form a realistic geometric model. Major organs in this model incl ude the liver, spleen, kidneys, lungs, heart, stomach, small intestine , large intestine, thyroid, pancreas, bone, marrow, and carcass. A sub cutaneous tumor mass also was included in the model. By accounting for small organ absorbed fractions and cross-organ beta doses, the MIRD m ethodology was extended from humans to mice for beta dose calculations . Results. Absorbed fractions of beta energy were calculated using the Berger's point kernels and the electron transport code EGS4. Except f or the tumor and carcass, the self-organ absorbed fractions ranged fro m 15% to 20% in smaller organs (the marrow and thyroid) to 65%-70% in larger organs (the liver and small intestine). Cross-organ absorbed fr actions also were calculated from estimates of the overlapping surface areas between organs. Conclusion. The mathematic mouse model presente d here provides more realistic organ dosimetry of radiolabeled monoclo nal antibodies in the nude mouse, which should, in turn, contribute to a better understanding of the correlation of biodistribution study re sults and organ-tumor toxicity information.