A Historical Perspective on the Use of Radionuclides for Therapy

Abstract

At present, standard of care for targeted therapy with radionuclides include; 131I for therapy of well-differentiated thyroid cancer; 89Sr chloride, and 153Sm-EDTMP for bone pain; radionuclide microembolization with either resin or glass microspheres; radiolabeled antibodies in lymphoma; metaiodobenzylguanidine for pheochromocytoma; radio peptide therapy for carcinoid, and other endocrine tumors. Growth in this sector of nuclear medicine has been modest. Recent advances in targeted radiotherapy are predicted to set the stage for a phase of rapid growth of the therapeutic aspects of nuclear medicine, as the most unique and potentially most distinctive utilitarian feature of our specialty. A plethora of targeting agents, ranging from small molecules to large nanoparticles offers many alternatives for pharmaceutical carrier of the radioactivity. In particular, major improvement in efficient production of a range of biologicals such as peptides, nanobodies, affibodies, and antibodies has occurred in the recent past and this has led to serious consideration of these agents as carriers of radioactivity after parenteral injection. In this brief overview, we highlight selected advances that have occurred in quantitative imaging, cancer biology, and radiobiology/radiochemistry which are likely to have significant short-term impact on radionuclide therapy. In regard to imaging improvements, there is now widespread availability of the potential for truly quantitative images, especially fusion images based on PET-CT, PET MRI, and SPECT-CT that have the ability to permit internal dosimetry as a guide to optimize therapeutic radionuclide dosing for better management of individual patients. Such imaging improvements, are leading to opportunities for use of theranostic radiotracers, whereby the same drug with minor changes is used for both diagnosis at tracer levels and therapy at tumoricidal levels. From a cancer biology point of view, targeted therapy of specific oncoproteins can restore some cancer cells to a more, nearly normal or differentiated state and this may have special relevance to thyroid cancers and other cancers (Pacak et al. ). Thus, non-iodine avid thyroid cancers can be differentiated to concentrate therapeutic levels of radioactive iodine or MIBG, by treatment with a short course of drugs that overcome the effects of specific oncogenic proteins. In regard to radiobiology/radiochemistry improvements, practical methods for accessing alpha emitters as therapeutic radionuclides have been developed.