A mouse model for calculating the absorbed beta-particle dose from (131)I- and (90)Y-labeled immunoconjugates, including a method for dealing with heterogeneity in kidney and tumor.
Flynn, A. A., Green, A. J., Pedley, R. B., Boxer, G. M., Boden, R. and Begent, R. H. J. A Mouse Model for Calculating the Absorbed Beta-Particle Dose from (131)I- and (90)Y-Labeled Immunoconjugates, Including a Method for Dealing with Heterogeneity in Kidney and Tumor. Radiat. Res. 156, 28-35 (2001). Conventional internal radiation dosimetry methods assume that the beta-particle energy is absorbed uniformly and completely in the source organ and that the radioactivity is distributed uniformly in the source. However, in mice, a considerable proportion of the beta-particle energy can escape the source organ, resulting in large cross-organ doses. Furthermore, the distribution of radioactivity is generally heterogeneous in kidney and tumor. Therefore, a model was developed to account for cross-organ doses and for the effects of heterogeneity in kidney and tumor in mice for two of the most important radionuclides used in therapy, (131)I and (90)Y. Most mouse organs were modeled as single-compartment ellipsoids or cylinders, while heterogeneity in kidney and in tumor was addressed by using two compartments to represent the cortex and the medulla and viable and necrotic cells, respectively. The dimensions of these models were taken from previous studies, with the exception of kidney and tumor, which were defined using radioluminography and mosaics of high-power microscopy images. The absorbed fractions in each compartment were calculated using beta-particle point dose kernels. The self-organ dose was significantly higher for (131)I compared to (90)Y in all compartments, but a considerable amount of beta-particle energy was shown to escape the source organ for both radionuclides, with as much as 85% and 36% escaping the marrow for (90)Y and (131)I, respectively. The cortex was found to occupy a greater proportion of the total kidney volume than the medulla, and consequently the self-dose was higher in the cortex. In addition, the thickness of the viable shell in the tumor increased with tumor size, as did the self-dose fractions in both necrotic and viable areas. This dosimetry model improves dose estimates in mice and gives a conceptual basis for considering dosimetry in humans.
Flynn
A A
AA
CRC Targeting and Imaging Group, Department of Oncology, Royal Free and University College Medical School, Royal Free Campus, Rowland Hill Street, London NW3 2PF, United Kingdom. a.flynn@ucl.ac.uk
Green
A J
AJ
Pedley
R B
RB
Boxer
G M
GM
Boden
R
R
Begent
R H
RH
D000818:Animals; D001610:Beta Particles / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000473:pathology / Q000532:radiotherapy; D004195:Disease Models, Animal; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use; D007457:Iodine Radioisotopes / Q000592:standards*; D007668:Kidney / Q000528:radiation effects*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011879:Radiotherapy Dosage / Q000592:standards; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays / Q000592:standards; D015021:Yttrium Radioisotopes / Q000592:standards*
D018796:Immunoconjugates; D007457:Iodine Radioisotopes; D015021:Yttrium Radioisotopes