Kennel, S. J., Mirzadeh, S., Eckelman, W. C., Waldmann, T. A., Garmestani, K., Yordanov, A. T., Stabin, M. G. and Brechbiel, M. W. Vascular-Targeted Radioimmunotherapy with the Alpha-Particle Emitter ²¹¹At. Radiat. Res. 157, 633–641 (2002).

Astatine-211, an α-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 α-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 α-particle emitters is an efficient therapy for small perivascular tumors and may be applicable to human disease when specific targeting agents are identified.