α-Particle Radiotherapy with 211At-Labeled Monodisperse Polymer Particles, 211At-Labeled IgG Proteins, and Free 211At in a Murine Intraperitoneal Tumor Model

Abstract

Four different chemical forms of the α-particle emitting radionuclide 211 At were injected intraperitoneally in mice inoculated intraperitoneally 30 hr in advance with 106 cells of the K13 murine hybridoma cell line. The different 211At forms were (a) free 211At, (b) 211At-labeled TP-3 nonspecific monoclonal antibody (211At-TP-3), (c) 211At-labeled human IgGκ (211At-hIgGκ), and (d) 211At-labeled monodisperse polymer particles (211At-MDPP). A significantly prolonged survival (P < 0.05) was observed with injected doses down to 7 kBq for the 211 At-MDPP, and down to 25 kBq for 211At-hIgGκ. There were no significant differences in survival between 211 At-MDPP, 211At-hIgGκ, and 211At-TP-3 at the dose level of 200 kBq. The group receiving 250 kBq free 211At per animal had a shorter survival than the three other forms at 200 kBq. The groups treated with 500, 200, and 65 kBq 211At-MDPP had a similar survival. The group given the highest dose of 211At-hIgGκ (275 kBq) had the highest fraction (50%) of long-term survivors of all groups. Biodistribution measurements and total body scintigrams in mice without tumor revealed that the free 211At was distributed all over the body within 10 min after injection while at 2 hr a high fraction of the 211 At-TP-3 and 211At-hIgGκ was still present intraperitoneally. In conclusion this study indicates that 211 At-labeled MDPP and 211At-labeled IgG's may be efficient tools for treatment of intraperitoneal superficial tumor cells and malignant ascites.