Technetium-99m-labeled receptor-specific small-molecule radiopharmaceuticals: Recent developments and encouraging results

The development of technetium-99m-labeled small-molecule radiopharmaceuticals directed at specific high-affinity binding sites, as are found in receptors for hormones and neurotransmitters, transport systems, and certain enzymes, is a natural outgrowth from the successful development of technetium radiopharmaceuticals for imaging flow and metabolism. Although many receptor specific radiopharmaceuticals labeled with PET and other SPECT isotopes already exist, the low cost and widespread availability of technetium-99m would make their Tc-99m-labeled counterparts much more accessible to the medical community. This review has four goals: (a) To survey and analyze critically the results of a flurry of research activity in this area in recent years, which has led to the preparation of a number of novel technetium labeled radiopharmaceuticals targeted at high-affinity sites, a few of which appear to be very promising; (b) to provide a conceptual analysis of how these agents are being designed; (c) to provide a context in terms of binding and uptake behavior by which these agents should be judged; and (d) to highlight emerging knowledge on the structure of receptors and related high-affinity binding biomolecules and their distribution, which may serve as reference points for understanding the results that have been obtained so far, and may be useful guides for future design. (C) 1997 Elsevier Science Inc.