Chemical and radiochemical considerations in radiolabeling with α-emitting radionuclides.

A review of chemical and radiochemical factors that must be considered when radiolabeling targeting agents with radionuclides is presented. The review discusses factors that are important in choice of radionuclide and choice of chelation or bonding reagents to use in the development of an α-emitting radiopharmaceutical. Chemical parameters, such as physical properties and pendant groups for radiolabeling, are reviewed. A major portion of the review outlines the development of chelates and labeling conditions for radiometals, and application of these reagents/conditions to radiometals. Acyclic and macrocyclic chelates containing amine and carboxylic acid coordination groups are highlighted, with examples of bifunctional chelates for biomolecule conjugation. Information is presented on over 60 radiometal-binding chelates. 211At radiolabeling is separated from that of radiometals, and the various reagents used for radiolabeling have been reviewed. Although not all 211At-labeling reagents are reviewed (due to another recent review), nearly 50 reagents studied in the development of pendant groups for labeling with 211At are described. The review also discusses how therapeutic doses of α-emitting radiopharmaceuticals can be affected by the radionuclide used and how radiation damage to the radiopharmaceutical can be minimized.