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 NIH Funding Opportunity Announcement (NOFO) PAR-23-164, issued by the National Institute of Mental Health (NIMH) and the National Institute on Aging (NIA), invites research grant applications focused on developing and testing PET (Positron Emission Tomography) and SPECT (Single Photon Emission Computed Tomography) imaging tracers in humans. The purpose of this initiative is to advance radioligands for use in clinical research related to mental health disorders and neurodegenerative diseases. Projects may target molecular structures linked to disease pathophysiology, aiding in drug development and biomarker discovery. Applications that include only preclinical animal studies are encouraged to apply to the companion NOFO (PAR-23-164). This program emphasizes developing tracers for targets within the central nervous system to enhance understanding of disease mechanisms and to support drug discovery. The goals include generating radiotracers that bind to brain-related molecular targets and support biomarker studies to track disease progression, evaluate target engagement, and guide dosing in therapeutic trials. NIMH is particularly interested in applications that identify potential therapeutic targets for mental illnesses and evaluate drug-target engagement in clinical studies. NIA’s focus includes imaging biomarkers for age-related brain disorders, such as Alzheimer’s disease, and the impact of cognitive decline on the brain. The research scope covers developing and validating radioligands for clinical research in human subjects, specifically for targets without redundant ligands already available in the pharmaceutical industry. Desired radioligands should demonstrate strong affinity, selectivity, and blood-brain barrier permeability, and applicants must include a feasibility assessment of the proposed tracer’s suitability for imaging in humans. Additionally, collaborative efforts between academic researchers and pharmaceutical industry partners are encouraged to facilitate the translation of promising radioligands into clinical research. Eligible applicants include U.S.-based and international higher education institutions, nonprofit and for-profit organizations, local and tribal governments, and other entities with the necessary infrastructure and expertise. Foreign entities may participate as well. NIH requires all applicants to complete the registration process with the System for Award Management (SAM), eRA Commons, and Grants.gov to be eligible for submission. Applications must follow the SF424 (R&R) Application Guide and meet specific formatting and documentation requirements. Required sections include a project narrative with justification for the tracer, feasibility of target detection, and a detailed research strategy that outlines the developmental path, timeline, and anticipated clinical applications of the radiotracer. Projects proposing clinical trials should detail the study design, recruitment strategies, data management, and statistical analyses. Additionally, applicants must comply with NIH data sharing policies and include a Data Management and Sharing Plan. Evaluation criteria emphasize the significance of the research, the qualifications of the investigators, innovation, the feasibility of the approach, and the scientific environment. Reviewers will assess how well the project addresses unmet needs in tracer development, the proposed study’s impact on mental and neurological health, and the practicality of achieving the desired tracer properties. Additional considerations include protections for human subjects, inclusion of diverse populations, and animal welfare compliance. Funding will be contingent on NIH appropriations, with no specified budget limit. The anticipated project period is up to five years, and applications requesting $500,000 or more in direct costs per year must consult NIH program staff prior to submission. Submission deadlines follow NIH standard cycles, with the next deadlines on June 5, 2024, and October 5, 2024.