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Description

This NIH funding opportunity (PAR-23-165) invites research grant applications focused on the preclinical development of novel radioligands for positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging. The goal is to develop imaging probes targeting molecular markers (e.g., receptors, intracellular messengers, disease-related proteins) implicated in central nervous system (CNS) disorders, primarily mental illnesses and age-related brain diseases.

The program emphasizes the use of rodent and nonhuman primate models for brain imaging and encourages incorporation of pilot or clinical feasibility evaluations within preclinical studies. The ultimate aim is to facilitate the broad application of neuroimaging probes that are fit-for-purpose in pathophysiological studies, drug discovery, biomarker development, and target engagement assessments.

This FOA does not support clinical trials or human studies; investigators interested in clinical assessments of novel radioligands should apply to the companion FOA PAR-23-164.

Background and Rationale

• There is a critical need for new PET and SPECT radioligands to image molecular targets involved in brain function and disorders.
• Existing radioligands are limited, restricting the ability to study disease mechanisms, drug-target interactions, and biomarker development.
• Development of new radiotracers will aid in understanding biological processes underlying mood, cognitive, and neurodegenerative disorders.
• Radioligands can help guide dosing of therapeutic agents and monitor disease progression and treatment efficacy.

Research Scope and Priorities

• Development of radioligands (agonists, antagonists, allosteric modulators) must be well justified with clear intended uses.
• Limited interest in developing tracers for targets already covered by existing radioligands or ongoing pharmaceutical efforts unless significant advantages are demonstrated.
• Interest in novel classes of ligands, especially those enabling exploration of agonist and allosteric modulator effects.
• Probes that monitor cellular processes linked to brain plasticity or pathology (e.g., neuroinflammation, neurogenesis, synaptic integrity, mitochondrial function) are encouraged.
• Applications should include feasible validation strategies for novel targets without existing pharmacologic tools.
• Partnerships between academia and industry are highly encouraged to accelerate development and application.

Examples of Research Activities

• Lead compound identification and synthesis with suitable binding affinity, selectivity, pharmacokinetics, and radiochemical properties.
• Preclinical pharmacology, toxicology, radiolabeling, autoradiography, and in vivo imaging in rodents and primates.
• Development of kinetic models and quantification methods for target engagement and pathophysiological studies.

Institute-Specific Interests

• National Institute of Mental Health (NIMH): Focus on mental disorders, innovative treatment targets, and probes to assess target engagement in experimental medicine clinical trials.
• National Institute on Aging (NIA): Focus on aging-related CNS changes, biomarkers, and therapeutic targets for cognitive decline, Alzheimer’s disease, and related dementias.

Important Notes

• Applications proposing radioligands for targets with existing PET/SPECT ligands require strong justification.
• Applicants must include a letter of support from a biological collaborator or advisor who will use the radiotracer to address clinical questions.
• A data management and sharing plan is required.
• This FOA is not for clinical trials; clinical assessments should be submitted to PAR-23-164.

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