Astatine-211, an alpha-particle emitter, was employed in a model system for vascular-targeted
radioimmunotherapy of small
tumors in mouse lung to compare its performance relative to other
radioisotopes in the same system.
Astatine-211 was coupled to the lung blood vessel-targeting
monoclonal antibody 201B with N-succinimidyl N-(4-[211At]astatophenethyl) succinamate linker. Biodistribution data showed that the conjugate delivered 211At to the lung (260-418% ID/g), where it remained with a
biological half-time of about 30 h. BALB/c mice bearing about 100 lung
tumor colonies of EMT-6 cells, each about 2000 cells in size, were treated with 211At-labeled
monoclonal antibody 201B. The administered activity of 185 kBq per animal extended the life span of treated mice over untreated controls.
Injections of 370 kBq, corresponding to an absorbed dose of 25-40 Gy, were necessary to eradicate all of the lung
tumors. Mice receiving 740 kBq of 211At-labeled
monoclonal antibody 201B developed
pulmonary fibrosis 3-4 months
after treatment, as did mice treated with 3700 kBq of the alpha-particle emitter 213Bi-labeled
monoclonal antibody 201B in previous work. Animals that were injected with 211At bound to untargeted
IgG or to
glycine, as control agents, also demonstrated
therapeutic effects relative to untreated controls. Control groups that received untargeted 211At required about twice as much administered activity for effective
therapy as did groups with lung-targeted
radioisotope. These results were not consistent with
radioisotope biodistribution and dosimetry calculations that indicated that lung-targeted 211At should be at least 10-fold more efficient for lung colony
therapy than 211At bound to nontargeting controls. The data showed that 211At is useful for vascular-targeted
radioimmunotherapy because lung
tumor colonies were eradicated in the mice. Work in this model system demonstrates that vascular targeting of alpha-particle emitters is an efficient
therapy for small perivascular
tumors and may be applicable to human disease when specific targeting agents are identified.