Development and Application of PET and SPECT Imaging Ligands as Biomarkers for Drug Discovery and for Pathophysiological Studies of CNS Disorders (R01 Clinical Trial Optional)

The National Institutes of Health (NIH) announces funding for the development and application of novel PET and SPECT imaging ligands as biomarkers for drug discovery and pathophysiological studies of central nervous system (CNS) disorders. This funding opportunity, reissued as PAR-25-036, is led by the National Institute of Mental Health (NIMH) and the National Institute on Aging (NIA) and encourages projects that develop new radioligands targeting receptors, intracellular messengers, or disease-related proteins implicated in brain disorders. These ligands will serve as tools for studying disease pathophysiology and assessing therapeutic target engagement, with applications in research on mental health and neurodegenerative diseases such as Alzheimer’s. The objective of this initiative is to increase the availability of PET and SPECT tracers, which are essential for visualizing molecular events in the brain, thus facilitating the identification of new therapeutic targets and validating biomarkers for CNS disorders. The NOFO seeks projects that not only create these tools but also make them widely available to enhance drug discovery, clinical trials, and biomarker development across the field. Applicants are encouraged to partner with pharmaceutical or biotech industry collaborators for faster development and application of these radiotracers. Specific areas of interest include imaging ligands that can assess neuroinflammation, synaptic integrity, mitochondrial function, and neurotransmitter systems. NIMH is particularly interested in ligands that can measure target engagement in clinical trials for mental health disorders, while NIA focuses on biomarkers relevant to neurodegenerative diseases such as Alzheimer’s. Proposals that target molecules for which tracers are already available are of lower priority unless a strong justification is provided for new approaches or advantages. Proposals may include lead compound identification, pre-clinical studies, in vivo imaging, and pharmacological assessments. Projects are required to justify the need for the radiotracer, including data on target density and affinity in human brain regions of interest. Applicants must also include detailed plans for tracer development and timelines, addressing critical properties such as blood-brain barrier penetration and metabolic stability. To support data sharing and standardization, NIH expects applicants to follow NIH data management policies, including the submission of Common Data Elements (CDEs) for human subjects studies to the NIMH Data Archive (NDA). The application budget is unrestricted but should reflect the project’s actual needs, with a maximum project duration of five years. Eligible applicants include higher education institutions, nonprofits, government entities, and foreign organizations. NIH encourages early submission to allow time for application corrections, with submission deadlines aligning with standard NIH cycles: February 5, June 5, and October 5 annually. Applications will undergo scientific merit review based on their significance, innovation, rigor, and feasibility, with specific attention to the research team’s expertise and the institutional environment. Decisions will consider peer review recommendations, relevance to program priorities, and available funds. Interested applicants should contact designated NIH program officers to discuss specific aims or alignment with program goals.