An overview of radiolabeled mAb directed approaches with an emphasis on the components (protein, radionuclide, chemistry) has been presented. After greater than two decades, mAb targeted therapies are generally recognized as making a significant impact in chemo-therapeutics. The FDA approvals of Zevalin and Bexxar have fueled renewed enthusiasm for developing mAb directed therapies. As such, their full potential is only beginning to be appreciated and understood.

However, despite the wealth of knowledge and capability in antibody engineering, the first two approved radiolabeled mAbs are murine in nature and subject to all of the limitations therein including immunogenicity and short biological half-lives. In many aspects actual clinical knowledge pertaining to the use of radiolabeled mAbs remains in its infancy. This is particularly true in regards to therapies beyond hematological diseases, including fractionated dosing schema and the rational construction of drug combination cocktail therapies in efforts to functionally integrate targeted radiation therapy with established chemotherapies and external beam therapies. Clear evidence exists that valuable results maybe achieved by execution of these strategies.

Dominance of mAb therapies for the lymphohema-topoietic malignancies and their success therein reflects inherent accessibility and radiosensitivity of these cancers. Literature consensus appears to support mAb-based therapies of solid tumor applied in the treatment of minimal residual micrometastatic disease and as an adjuvant component of a multi-modality treatment regimen. However, limitations were recognized through the investigations with less than optimal targeting agents, suboptimal chemistry, incorrect radionuclide choice, and a less than rational experimental design. As such there remains a continuing effort to refine and optimize all of the components to improve efficacy and minimize toxicity. The future will prove exciting due to the rational exploration and application of the cumulative knowledge towards making targeted radiation therapy a reality and mainstream component for the treatment and management of cancer.

Acknowledgements. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, and Center for Cancer Research.

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