Center without Walls for PET Ligand Development for Alzheimer's disease related dementias (ADRDs) (U19 Clinical Trial Optional) | RFA NS 19 014

Opportunity Information: Apply for RFA NS 19 014

The NIH funding opportunity RFA-NS-19-014, titled "Center without Walls for PET Ligand Development for Alzheimer's disease related dementias (ADRDs) (U19 Clinical Trial Optional)," is a cooperative agreement designed to accelerate the creation and early clinical testing of new PET radioligands for ADRD research. The central goal is to produce imaging tracers that can reliably detect specific proteinopathies or other disease-relevant biological processes tied to the human biology of ADRDs, helping the field move beyond general clinical symptom labels and toward objective, in vivo measures of pathology. In practical terms, the FOA is aimed at building an end-to-end translational pipeline that can take promising ligand concepts and move them through screening, optimization, and initial human evaluation.

The scope of work explicitly spans multiple stages of development. Supported activities include in vitro screening of existing candidate ligands using human ADRD brain tissue (to ensure binding and selectivity are relevant to real human disease), medicinal chemistry to design new compounds or improve the performance of existing ones (for example, improving specificity, selectivity, affinity, brain penetration, and reducing off-target binding), initial in vivo screening in appropriate animal models (to assess pharmacokinetics, brain uptake, specificity, and signal-to-noise), and radioligand formulation plus first-in-human testing. The overall expectation is that the funded Center will function like an integrated development engine, continuously prioritizing candidates, troubleshooting weaknesses, and pushing the best-performing ligands forward until at least some reach early clinical evaluation.

A defining feature is the required "Center without Walls" structure, meaning the program is intended to operate as a coordinated consortium rather than a single-lab effort. Applications must be organized around a set of shared cores and multiple interdependent research projects, with clear workflows and milestone-driven plans. At minimum, applicants must propose an Administrative Core (to manage operations, timelines, reporting, and coordination), a Medicinal Chemistry Core (to generate and optimize chemical entities and support structure-activity work), and a Clinical Core (to handle radioligand production readiness, regulatory and clinical translation, and first-in-human studies). In addition, the application must describe a scientific governance structure that lays out decision-making processes, prioritization criteria, and how the consortium will manage go/no-go decisions based on milestone data.

Beyond the cores, the FOA requires at least two distinct research projects, each with milestone plans. Those milestones need to explicitly address practical workflows for screening both existing ligands and newly derived compounds against human ADRD tissue and in appropriate animal models. The emphasis on milestones signals that the program is meant to be managed with clear performance benchmarks, enabling the consortium and NIH program staff to judge whether candidate ligands are advancing efficiently toward the next stage. The FOA also stresses that synergy has to be obvious: the proposed projects and cores should be so interconnected that the key aims would not be realistically achievable as separate, loosely related grants. In other words, this is not a bundle of independent projects; it is a single coordinated development program with shared infrastructure and coordinated decision-making.

The opportunity is positioned as a response to ADRD challenges highlighted in the 2016 update to the National Plan to Address Alzheimer's Disease, reflecting a broader federal priority to improve tools for diagnosis, staging, and therapy development across dementias beyond typical Alzheimer's disease alone. PET ligands that can measure specific pathologies in living patients are increasingly important for patient stratification in trials, understanding mixed pathologies, tracking disease progression, and verifying target engagement for new therapeutics. This FOA is set up to push that tool-building work forward by funding the chemistry, biology, imaging, and early clinical translation together under one coordinated structure.

From an administrative standpoint, this is a discretionary NIH opportunity using the cooperative agreement mechanism (U19), which typically involves substantial NIH programmatic involvement compared to standard investigator-initiated grants. The activity category is health, and the CFDA numbers listed are 93.853 and 93.866. The original closing date shown is February 13, 2019, and the FOA creation date is December 11, 2018.

Eligibility is broad across U.S.-based organizations and includes many government and nonprofit entities as well as academic and industry participants. Eligible applicants include state, county, and local governments; special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized Native American tribal governments; certain non-federally recognized tribal organizations; public housing authorities/Indian housing authorities; nonprofits with and without 501(c)(3) status; for-profit organizations (other than small businesses) and small businesses; and other eligible organizations. The FOA also highlights outreach to and eligibility for specific institution types such as HBCUs, Hispanic-serving institutions, Tribally Controlled Colleges and Universities, Alaska Native and Native Hawaiian Serving Institutions, and Asian American Native American Pacific Islander Serving Institutions, as well as faith-based or community-based organizations and eligible federal agencies.

Foreign eligibility is restricted in a nuanced way. Non-domestic (non-U.S.) entities and foreign institutions are not eligible to apply directly as the applicant organization. However, non-domestic components of U.S. organizations are eligible, and foreign components (as defined in the NIH Grants Policy Statement) are allowed, meaning an otherwise eligible U.S. applicant can include certain international collaborations or activities when justified and compliant with NIH policy.

Overall, the FOA is best understood as a structured, milestone-driven consortium program meant to deliver tangible PET radioligand candidates for ADRD biology, moving from tissue-based validation and chemistry optimization through animal testing and into first-in-human studies, with the required cores and governance ensuring that the pieces operate as a single, efficient development pipeline rather than isolated academic projects.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Center without Walls for PET Ligand Development for Alzheimer's disease related dementias (ADRDs) (U19 Clinical Trial Optional)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.853, 93.866.
• This funding opportunity was created on 2018-12-11.
• Applicants must submit their applications by 2019-02-13. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

Apply for RFA NS 19 014

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