Alpha-particle radiotherapy with 211At-labeled monodisperse polymer particles, 211At-labeled IgG proteins, and free 211At in a murine intraperitoneal tumor model.
Four different chemical forms of the alpha-particle emitting radionuclide 211At were injected intraperitoneally in mice inoculated intraperitoneally 30 hr in advance with 10(6) 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 IgG kappa (211At-hIgG kappa), 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 211At-MDPP, and down to 25 kBq for 211At-hIgG kappa. There were no significant differences in survival between 211At-MDPP, 211At-hIgG kappa, 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-hIgG kappa (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 211At-TP-3 and 211At-hIgG kappa was still present intraperitoneally. In conclusion this study indicates that 211At-labeled MDPP and 211At-labeled IgG's may be efficient tools for treatment of intraperitoneal superficial tumor cells and malignant ascites.
Larsen
R H
RH
Department of Chemistry, University of Oslo, Norway.
Hoff
P
P
Vergote
I B
IB
Bruland
O S
OS
Aas
M
M
De Vos
L
L
Nustad
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001246:Astatine / Q000032:analysis / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006825:Hybridomas / Q000737:chemistry / Q000000981:diagnostic imaging / Q000528:radiation effects*; D007074:Immunoglobulin G / Q000032:analysis / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D051379:Mice; D008807:Mice, Inbred BALB C; D011108:Polymers; D011877:Radionuclide Imaging; D015996:Survival Rate; D013997:Time Factors; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D011108:Polymers; D001246:Astatine