The development of effective therapeutic radiopharmaceuticals requires careful consideration in the selection of the radionuclide. The in vivo targeting and clearance properties of the carrier molecule must be balanced with the decay properties of the attached radionuclide. Radionuclides for therapeutic applications fall into three general categories: beta-particle emitters, alpha-particle emitters, and Auger and Coster-Kronig-electron emitters following electron capture. Alpha particles and Auger electrons deposit their energy over short distances with a high LET that limits the ability of cells to repair damage to DNA. Despite their high levels of cytotoxicity, the relatively short range of alpha particles requires binding of the carrier molecule to most cancer cells within a tumor in order to be effective. Because of the extremely short range of Auger electrons, the radionuclide must be carried directly into the nucleus to elicit high radiotoxicity, making it necessary to deliver the radionuclide to every cell within a tumor cell population. These characteristics impose rigid restrictions on the nature of the carrier molecules for these types of particle emitters but successful targeting of these types of radionuclides could result in high therapeutic ratios. Most beta-emitting radionuclides are produced in nuclear rectors via neutron capture reactions; however, a few are produced in charged-particle accelerators. For radionuclides produced by direct neutron activation, the quantities and specific activities that can be produced are determined in large part by the cross-section of the target isotope and the flux of the reactor. Many applications (e.g., therapeutic bone agents, radiolabeled microspheres, radiocolloids) do not require high-specific activities and can therefore utilize the wide range of radionuclides that can be produced in sufficient quantity by direct neutron activation. Other applications (e.g., MAb labeling) require high-specific activity radionuclides in order to deliver a sufficient number of radionuclide atoms to the target site without saturating the target or compromising the integrity of the carrier molecule. Most radionuclides, produced at NCA levels in reactors, are produced via indirect reactions. High-specific activity beta emitters can also be obtained from radionuclide generator systems where the longer-lived parent radionuclide may be obtained from direct neutron activation, as a fission product, or from charged-particle accelerators. It is essential that the half-life of a radionuclide used in RNT be compatible with the rates of localization in target tissues and clearance of the carrier molecule from normal tissues. This consideration is especially important for the various MAbs and their fragments that are currently under investigation as carrier molecules to RIT.(ABSTRACT TRUNCATED AT 400 WORDS)