Chapter 4: Design and Synthesis of Radiopharmaceuticals for SPECT Imaging

Nuclear medicine molecular imaging modalities such as single-photon emission computed tomography (SPECT) and positron emission tomography (PET) imaging play increasingly important roles in both diagnostic medicine and Big Pharma's drug discovery programs. In diagnostic medicine, PET and SPECT imaging are used for early diagnosis of disease and to monitor patient response to therapy. In drug discovery, such imaging techniques are used to make critical decisions about lead candidate efficacy, as well as to track the impact of experimental drugs in clinical trials. If this growth in the use of nuclear medicine imaging modalities is to continue, there must be concomitant development of increasingly elegant radiopharmaceuticals with which to realize the desired applications. The adaptation of potentially bioactive molecules into radiopharmaceuticals is frequently not trivial. Scaffolds have to be designed for rapid and efficient incorporation of suitable short-lived radionuclides, whilst maintaining affinity for the biological target in question. Moreover, radiopharmaceuticals are frequently prepared (or compounded) locally and so the chemistry has to allow straightforward introduction of the radionuclide and the preparation of doses suitable for immediate human use. This chapter introduces the art and science of synthesizing radiopharmaceuticals for application in SPECT imaging. Strategies for radiopharmaceutical preparation and quality control are introduced, and proof-of-concept is illustrated through examples of such drugs currently used in clinical SPECT imaging.