Despite much effort on the treatment of cancer, many patients still succumb to the disease. Approximately 250,000 patients each year develop distant metastases following treatment for primary tumors. An effective adjuvant treatment is needed for these patients. Alpha radiotherapy (He atoms) is especially promising for the treatment of micrometastatic disease due to qualities of high amounts of energy given off within several cell diameters. Feasibility has been shown in a Phase I SBIR study for the use of antibody pretargeting to selectively and efficiently deliver (212)Pb to tumors which decays to the clearance of remaining conjugate from circulation and delivery to radiotherapy via (212)Pb radiochelate-biotin. The high affinity strepatavidin-biotin results in efficient capture and stable binding of the radiation. The reagents developed for pretargeting have been validated in Phase I and in the Phase II study, further characterization of the system and radiotherapeutic efficacy and toxicology will be done in solid tumor models to provide support for Phase I clinical trials. Antibody pretargeting offers a unique opportunity to efficiently and selectively deliver high potency alpha radiotherapeutics such as offered by the (212)Pb/(212)Bi system to patients with small volume, metastatic disease.
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