In vivo molecular targeted radiotherapy

Abstract

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 131I-sodium iodide for the treatment of hypothyroidism and differentiated thyroid carcinoma and 32P-sodium phosphate for the treatment of polycythaemia vera. In recent years the use of bone seeking agents 89Sr, 153Sm and 186Re for the palliation of bone pain have become widespread and considerable progress has been evident with the use of 131I-MIBG and 90Y-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 90Y and 131I 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 188Re 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.

Phosphorus-32, a Clinically Available Drug, Inhibits Cancer Growth by Inducing DNA Double-Strand Breakage

“…In this context, it is noteworthy that no obvious toxic side effects occurred in any of the model systems we have studied to date. The other concern with its use in these benign hematologic disorders has been an increased incidence of subsequent acute myeloid leukemia (AML) [ 37 , 38 ], but in patients with advanced solid tumors this is less of a concern, since subsequent AML occurs in only 10% ten years after 32 P treatment [ 39 ]. Moreover, this new indication and method of use for an existing drug saves considerable time and expense, relative to the investment required for new anticancer agents.…”

αVβ3 Integrin-Targeted Radionuclide Therapy with 64Cu-cyclam-RAFT-c(-RGDfK-)4

“…Molecular-targeted radionuclide therapy (MTRT), which is a promising cancer treatment option, is performed by the systemic administration of a specific molecular vehicle, that is, antibody, peptide or small organic molecule that is radiolabeled with a cytocidal energy-releasing radionuclide (a-or b À -particle emitter or Auger electron emitter) to elicit a therapeutic effect on the targeted tumoral lesions (1)(2)(3)(4). The key advantages such as rapid blood clearance, tissue penetration capability, low immunogenicity, and relatively easy and cost-effective production, have made the peptide-based MTRT more attractive as a treatment strategy with clinical-translational potential (4)(5)(6).…”

Targeted Radionuclide Therapy: Proceedings of a Joint Workshop Hosted by the National Cancer Institute and the Society of Nuclear Medicine and Molecular Imaging

“…Radioimmunotherapy describes targeted therapy with radiolabeled monoclonal antibodies. Molecular targeted therapy describes both radionuclide and nonradionuclide therapy (8). TRT describes techniques in which one or more radionuclides, usually but not always incorporated into a conjugate or attached to a ligand, are administered with the goal of providing targeted therapy at the cellular or molecular level.…”