TY - JOUR T1 - Imaging Biomarkers for Central Nervous System Drug Development and Future Clinical Utility: Lessons from Neurodegenerative Disorders JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 12 LP - 19 DO - 10.2967/jnumed.122.264773 VL - 64 IS - 1 AU - John P. Seibyl Y1 - 2023/01/01 UR - http://jnm.snmjournals.org/content/64/1/12.abstract N2 - Diseases of the central nervous system are common and often chronic conditions associated with significant morbidity. In particular, neurodegenerative disorders including Alzheimer and Parkinson disease constitute a major health and socioeconomic challenge, with an increasing incidence in many industrialized countries with aging populations. Recent work has established the primary role of abnormal protein accumulation and the spread of disease-specific deposits in brain as a factor in neurotoxicity and disruption of functional networks. A range of therapeutics from small molecules to antibodies targeting these proteinopathies are now in phase 2 and phase 3 clinical trials. These studies are methodologically challenging because of difficulty in accurately diagnosing early disease, the slow and variable rates of progression between individuals, and efficacy measures that may be cofounded by symptomatic improvements due to treatment but not reflecting disease course modification. Further, the ideal candidates for these treatments would be at-risk, or premanifest, persons in whom the pathologic process of the neurodegenerative disorder has begun but who are clinically normal and extremely difficult to identify. Scintigraphic imaging with PET and SPECT in trials offers the opportunity to interrogate pathophysiologic processes such as protein deposition with high specificity. This review summarizes the current implementation of these imaging biomarkers and the implications for future management of neurodegenerative disorders and central nervous system drug development in general. ER -