In vivo molecular targeted radiotherapy

Unsealed radionuclides have been in clinical therapeutic use for well over half a century. Following the early inappropriate clinical administrations of radium salts in the early 20th century, the first real clinical benefits became evident with the use of (131)I-sodium iodide for the treatment of hypothyroidism and differentiated thyroid carcinoma and (32)P-sodium phosphate for the treatment of polycythaemia vera. In recent years the use of bone seeking agents (89)Sr, (153)Sm and (186)Re for the palliation of bone pain have become widespread and considerable progress has been evident with the use of (131)I-MIBG and (90)Y-somatostatin receptor binding agents. Although the use of monoclonal antibody based therapeutic products has been slow to evolve, the start of the 21st century has witnessed the first licensed therapeutic antibody conjugates based on (90)Y and (131)I for the treatment of non-Hodgkin's lymphoma. The future clinical utility of this form of therapy will depend upon the development of radiopharmaceutical conjugates capable of selective binding to molecular targets. The availability of some therapeutic radionuclides such as (188)Re produced from the tungsten generator system which can produce activity as required over many months, may make this type of therapy more widely available in some remote and developing countries.Future products will involve cytotoxic radionuclides with appropriate potency, but with physical characteristics that will enable the administration of therapeutic doses with the minimal need for patient isolation. Further developments are likely to involve molecular constructs such as aptamers arising from new developments in biotechnology.Patient trials are still underway and are now examining new methods of administration, dose fractionation and the clinical introduction of alpha emitting radiopharmaceutical conjugates. This review outlines the history, development and future potential of these forms of therapy.