Developmental Trends in Targeted Radionuclide Therapy: Biological Aspects

Summary

Targeted radionuclide therapy of hematopoietic malignancies in the clinical setting has been achieved and similar successes with solid tumors and cells disseminated from them are likely within reach. Recombinant technologies have led to the development of a number of new targeting agents and the evaluation of a number of putative new targets is currently in progress. These advances are currently under evaluation in the preclinical setting and are expected to transition into clinical trials before long. Many of these new agents exhibit both improved pharmacological properties and enhanced cellular retention, both of which may lead to substantial improvements over existing compounds. In addition, our knowledge of basic radiobiology and its impact on the different modes of cell death is rapidly expanding, leading to new understanding in the fundamental differences between hematopoietic and epithelial tumor cells. Such knowledge will likely have a significant influence on the development of future treatment modalities. Furthermore, the complex interactions between radiation induced intracellular signaling pathways and the crucial observation that low dose radiation (e.g. less than 15 Gy) is able to significantly affect the growth of disseminated solid tumors cells suggests to us that a new era in targeted radionuclide therapy may soon be here.