Development and Application of PET and SPECT Imaging Ligands as Biomarkers for Drug Discovery and for Pathophysiological Studies of CNS Disorders (R01 Clinical Trial Not Allowed)

The National Institutes of Health (NIH), through the National Institute of Mental Health (NIMH) and the National Institute on Aging (NIA), has released a funding opportunity for research focused on the development of positron emission tomography (PET) and single photon emission computed tomography (SPECT) radiotracers. This grant supports projects aimed at preclinical research on radioligands that can advance understanding of brain disorders, facilitate drug discovery, or provide biomarkers to assess disease progression and treatment efficacy. This opportunity falls under the R01 Research Project Grant mechanism, which supports individual projects without clinical trials. Applicants interested in clinical assessments should apply to the companion R01 NOFO PAR-23-164. This grant encourages innovative research on molecular targets related to neurotransmitter systems, intracellular messengers, or disease-related proteins involved in brain function and behavioral disorders. It aims to increase the availability of PET and SPECT radiotracers to study neurological and psychiatric conditions, including Alzheimer’s disease, mood disorders, and neurodegenerative diseases. Potential uses of these radioligands include tracking brain plasticity, monitoring neuroinflammation, or validating new therapeutic targets through preclinical models. The program encourages partnerships between academic researchers and the pharmaceutical industry to accelerate tracer development. The development of radiotracers must be well justified, with applications focusing on targets not already well served by existing ligands unless the proposed research offers significant advancements. Proposed radioligands should be fit-for-purpose, ensuring that they provide meaningful insights into brain pathophysiology or support therapeutic development. The research should address key aspects such as ligand binding, target engagement, pharmacokinetics, and imaging reproducibility. While most radiotracers to date have been orthosteric antagonists, this funding opportunity seeks to expand the scope by exploring agonists, allosteric modulators, or probes for cellular processes like mitochondrial function and synaptic integrity. Projects can involve lead compound identification, chemical synthesis, pharmacological testing, and preclinical imaging in rodent or primate models. Applications must include detailed plans for radiolabeling, biodistribution studies, and validation models. Investigators should also demonstrate the ability to quantify tracer kinetics and binding characteristics, including factors like blood-brain barrier penetration. While no human studies are supported under this specific NOFO, collaborations with clinical scientists are encouraged to ensure that the tracers align with future therapeutic applications. Eligible applicants include higher education institutions, nonprofits, small businesses, and government organizations. Domestic and international collaborations are permitted, with foreign institutions eligible to apply. The award budget is flexible and should reflect the actual needs of the project, with a maximum project duration of five years. There are no cost-sharing requirements for this grant. Applicants can submit new, resubmission, or revised applications, provided each submission is scientifically distinct. Applications must adhere to NIH’s SF424 (R&R) guidelines and address data management and sharing requirements. Investigators are required to register with the System for Award Management (SAM) and eRA Commons before submission. NIH encourages the use of common data elements (CDEs) to facilitate data sharing and interoperability across studies. The first submission deadline under this NOFO is February 5, 2024, with subsequent deadlines in June, October, and February each year until the program’s expiration on January 8, 2025. Proposals will be reviewed for scientific merit, innovation, and relevance to program priorities. Reviewers will assess the significance of the proposed radiotracers, the feasibility of target detection, and the involvement of collaborators from clinical or pharmaceutical fields. Successful applicants will be notified through a formal Notice of Award and will be expected to submit annual performance reports. The award supports preclinical research that lays the foundation for future clinical studies and contributes to improved understanding and treatment of brain disorders.