| Abstract: |
The use of monoclonal antibodies to deliver radioisotopes directly to tumor cells has become a promising strategy to enhance the antitumor effects of native antibodies. Since the α-and β-particles emitted during the decay of radioisotopes differ in significant ways, proper selection of isotope and antibody combina tions is crucial to making radioimmunotherapy a standard therapeutic modality. Because of the short pathlength (50-80 μm) and high linear energy transfer (≃100 keV/μm) of α-emitting radioisotopes, targeted α-particle therapy offers the potential for more specific tumor cell killing with less damage to surrounding normal tissues than β-emitters. These properties make targeted α-particle therapy ideal for the elimination of minimal residual or micrometastatic disease. Radioimmunotherapy using α-emitters such as 213Bi, 211At, and 225Ac has shown activity in several in vitro and in vivo experimental models. Clinical trials have demonstrated the safety, feasibility, and activity of targeted α-particle therapy in the treatment of smallvolume and cytoreduced disease. Further advances will require investigation of more potent isotopes, new sources and methods of isotope production, improved chelation techniques, better methods for pharmacokinetic and dosimetric modeling, and new methods of isotope delivery such as pretargeting. Treatment of patients with less-advanced disease and, ultimately, randomized trials comparing targeted α-particle therapy with standard approaches will be required to determine the clinical utility of this approach. |
