Radiohalogens for radioimmunotherapy
The selective delivery of cytotoxic radionuclides to malignant cell populations is the central objective of radioimmunotherapy. The impact of radioimmunotherapy on the clinical management of cancer has generally been limited, particularly for the treatment of solid tumors. Nonetheless, labeled monoclonal antibody (mAb) therapy remains an attractive approach for cancer treatment with the caveat that its success will depend on improving mAb specificity, delivery, and radiolabeling. In preclinical settings, promising advances have been achieved in these three areas and they will be investigated soon in clinical trials. First, molecular biological techniques have demonstrated that malignant transformation can lead to gene rearrangement, yielding truly tumor-specific targets. For example, an epidermal growth factor receptor deletion mutant has been identified which is present on several tumor cell populations but not on normal tissues, and mAbs specific for this receptor have been developed (1). Second, efforts to improve mAb tumor delivery not only have involved the generation of novel molecular constructs (2,3) but also have been directed at augmenting mAb tumor uptake through modification of tumor hemodynamics (4). And third, a considerable effort has been directed at improving mAb radiolabeling. In that regard, the current status of mAb radiohalogenation approaches will be summarized in this review.
