Therapeutic radiopharmaceuticals

Site-specific radiopharmaceuticals that are labeled with particle-emitting radionuclides offer opportunities for selective in vivo cellular destruction. A limited number of radiolabeled drugs are being routinely used for treatment of cancers and other diseases in humans. The patient outcomes resulting from their utilization demonstrate the value of these types of agents for treatment of diffuse and otherwise untreatable conditions. One of the inherent problems associated with the design of novel radiolabled compounds relates to development of radiolabeled conjugates that have the capacity for achieving specific tissue targeting to meet therapeutic objectives with an acceptable degree of systemic toxicity. Critical to the success of using unsealed therapeutic radioactive agent for cancer therapy is the need for the development of compounds labeled with particle-emitting radionuclides that possess the following attributes, either alone or in combination: (1) demonstrated ability to in vivo target cancer cells selectively relative to normal cells, (2) capability to achieve sufficiently high radioactivity concentration and spacial distributions in the cellular matrixes of tumors to irradiate all cells in the tumor, (3) ability to achieve long-term residualization in the tumor for delivery of cytotoxic radiation doses to the tumor, and (4) capability to clear the radiolabeled drug or its radioactive metabolites efficiently from nontarget tissues (particular radiosensitive normal cells) in order to minimize radiation-induced side effects. To successfully design, synthesize, and evaluate effective therapeutic radiopharmaceuticals, there is a great need for involvement of synthetic, organic, analytical, inorganic, and radiochemists working in concert with scientists with expertise in the biochemical, pharmacological, physiological, and oncological sciences. Interdisciplinary efforts of this level will provide reasonable possibilities for the efficient development of radiopharmaceuticals capable of delivering cytotoxic doses of radiation in high specificity to cancerous tumors. © 1999 American Chemical Society.