Biomarkers in Randomized Clinical Trials: Positron Emission Tomography and Nuclear Medicine Techniques

Background: Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are nuclear medicine techniques that utilize the tracer principle to image biological processes using radiolabeled molecules. Numerous PET and SPECT radiopharmaceuticals have been developed over the years that qualify as biomarkers for neurological disorders. Summary: This chapter reviews the use of PET and SPECT in neurological clinical trials, and emphasizes the concepts and lessons learned from these experiences. Key Messages: Key considerations for successful use of PET or SPECT imaging as biomarkers in neurological randomized trials include: (1) in vivo behavior of the radiotracer and the PET or SPECT imaging parameter studied should reflect an essential aspect of the underlying pathology and/or pathophysiology of the disease under question, (2) the underlying biological target and radiotracer distribution should have the potential to vary with treatment under study conditions, and adjustments must be made for any other known changes (e.g. physiological) that may occur over time, (3) image reconstruction techniques and quantitative or semiquantitative image analysis approaches should be robust and standardized across trial sites, and (4) newer molecular targets should be explored based on insights obtained from basic science research and translational observations. Successful implementation of PET and SPECT in clinical trials and practice has a highly significant potential to contribute towards improving outcomes and clinical care for patients with neurological disorders.