Atom | 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)

Funder: National Institutes of Health (NIH)

Funding Amounts: Budgets are not limited but must reflect actual project needs; project periods up to 5 years.

Summary: Supports preclinical development of novel PET and SPECT radioligands for brain imaging in animal models to aid drug discovery and pathophysiological studies of CNS disorders, including pilot or clinical feasibility evaluations.

Key Information: Clinical trials are not allowed under this FOA; human studies should apply to companion FOA PAR-23-164. Applications must include a biological collaborator or advisor and a data management and sharing plan.

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.

Due Dates

Applications are due by 5:00 PM local time on the following standard NIH due dates:

February 5, 2025 (New)
March 5, 2025 (Renewal/Resubmission/Revision)
May 7, 2025 (AIDS-related)
June 5, 2025 (New)
July 5, 2025 (Renewal/Resubmission/Revision)
September 7, 2025 (AIDS-related)
October 5, 2025 (New)
November 5, 2025 (Renewal/Resubmission/Revision)

Applicants are encouraged to apply early to allow time for corrections.

Note: This FOA expires on January 8, 2025, per Notice NOT-MH-25-025.

Funding Amount

Application budgets are not limited but must reflect the actual needs of the proposed project.
Project periods may be up to 5 years.
Number of awards depends on NIH appropriations and meritorious applications.

Eligibility

Eligible Applicants

Public and private institutions of higher education (including HBCUs, HSIs, TCCUs, AANAPISIs)
Nonprofits with or without 501(c)(3) status (excluding institutions of higher education)
For-profit organizations (including small businesses)
State, county, city, township, and special district governments
Federally recognized and other Native American tribal governments and organizations
Independent school districts, public housing authorities
Foreign institutions and foreign components of U.S. organizations are eligible

Principal Investigators

Any individual with the skills, knowledge, and resources to carry out the research.
Individuals from underrepresented groups are encouraged to apply.
Multiple PD/PI applications are allowed.

Registrations Required

System for Award Management (SAM)
eRA Commons
Grants.gov
NATO Commercial and Government Entity (NCAGE) Code (for foreign organizations)

Cost Sharing

Not required.

Application Process

Applications must be submitted electronically via Grants.gov and tracked in eRA Commons.
Use SF424 (R&R) Application Guide and FORMS-H application packages.
Include a Letter of Support from a biological collaborator or advisor.
Include a Data Management and Sharing Plan as per NIH policy.
Follow all instructions for Research Strategy, including justification of target, feasibility, and development plan for the radiotracer.
Include Resource Sharing Plans for protocols, ligands, and analytical tools.
Limited appendix materials allowed (e.g., blank questionnaires).
Clinical trials are not allowed under this FOA.

Application Review

Review Criteria

Significance: Importance of the problem, justification for radiotracer development, potential impact.
Investigator(s): Expertise and track record, involvement of biological collaborator.
Innovation: Novelty of approach, methodology, or instrumentation.
Approach: Feasibility, rigor, plans to address challenges, timeline for radiotracer development.
Environment: Institutional support, resources, and collaborative arrangements.

Additional Review Considerations

Protection of human subjects (if applicable)
Inclusion of women, minorities, and individuals across the lifespan (if applicable)
Use of vertebrate animals (if applicable)
Biohazards
Resource sharing plans
Authentication of key biological/chemical resources

Review and Selection

Applications undergo NIH peer review for scientific merit.
Funding decisions consider scientific merit, availability of funds, and program priorities.

Contact Information

Contact Type	Name	Organization	Phone	Email
Scientific/Research Contact	Enrique Michelotti, Ph.D.	National Institute of Mental Health (NIMH)	301-443-5415	michelottiel@mail.nih.gov
Scientific/Research Contact	Alessandra Rovescalli, Ph.D.	National Institute on Aging (NIA)	301-555-1212	rovescaa@nih.gov
Grants Management Contact	Heather Weiss	National Institute of Mental Health (NIMH)	301-443-4415	weissh@mail.nih.gov
Grants Management Contact	Philip Smith	National Institute on Aging (NIA)	301-555-1212	philip.smith2@nih.gov
Application Submission Support	eRA Service Desk	NIH	301-402-7469 or 866-504-9552 (Toll Free)	https://www.era.nih.gov/need-help
General Grants Information	-	NIH	301-480-7075	GrantsInfo@nih.gov
Grants.gov Support	-	-	800-518-4726	support@grants.gov

Additional Information

This FOA is a reissue of PAR-20-037.
Applicants should consult the CNS Radiotracer Table to avoid duplication.
Applicants are encouraged to contact NIH Program Officers to discuss target needs.
All awards are subject to NIH Grants Policy Statement terms and federal regulations.
Applicants must comply with NIH policies on data management, sharing, and human subjects protections.
The FOA is not subject to intergovernmental review (E.O. 12372).
The FOA includes instructions for handling human fetal tissue, select agents, and other regulatory requirements.

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)