Development and Application of PET and SPECT Imaging Ligands as Biomarkers for Drug Discovery and for Pathophysiological Studies of CNS Disorders (R21/R33) | Apply Online

FAQs: NIH PAR 13-158 (R21/R33) PET and SPECT Imaging Ligands for CNS Biomarkers

What is NIH PAR 13-158?

PAR 13-158 is an NIH funding opportunity announcement titled "Development and Application of PET and SPECT Imaging Ligands as Biomarkers for Drug Discovery and for Pathophysiological Studies of CNS Disorders (R21/R33)." It supported research to create and test new PET or SPECT imaging agents (radioligands) intended for use in the human brain as biomarkers.

What was the main goal of this funding opportunity?

The central goal was to encourage development of novel PET and SPECT radioligands for the brain, with an emphasis on moving beyond chemistry and assay work to include early feasibility evaluation. Projects were expected to generate evidence that a ligand could realistically function as a biomarker, including work such as pilot preclinical studies, model development enabling quantitative imaging, and/or clinical studies.

What kinds of imaging technologies did the FOA focus on?

The announcement focused on radioligands for positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging in the context of central nervous system (CNS) research.

What is an imaging ligand (radioligand) in the context of this FOA?

In this program, an imaging ligand (radioligand) is a molecule labeled for PET or SPECT imaging that is designed to bind to a specific molecular target in the living brain so that the target or process can be measured noninvasively and quantitatively.

What does it mean that the ligands are intended to be "biomarkers"?

The FOA emphasized imaging ligands as biomarkers, meaning tools that measure biological processes in the living brain in ways useful for understanding CNS disease mechanisms or evaluating therapeutics. The intent was practical utility in drug discovery and/or pathophysiological studies, not just early-stage experimental probes.

Did proposals need to include feasibility testing, or could they stop at chemistry development?

Proposals were expected not to stop at chemistry or assay development alone. The FOA clearly expected some form of early feasibility evaluation, such as pilot preclinical imaging, model development supporting quantitative imaging, and/or clinical studies demonstrating potential to function as a biomarker in humans.

What types of early feasibility work were mentioned?

The announcement described examples of early feasibility evaluation including pilot preclinical studies, model development work that enables quantitative imaging, and/or clinical studies to evaluate whether the ligand can function as a biomarker in humans.

What is the R21/R33 phased innovation structure used by this FOA?

This opportunity used the NIH R21/R33 phased innovation structure. It is designed for high-impact projects that begin with an exploratory proof-of-concept phase (R21) and, if milestones are met, transition to a more advanced developmental phase (R33).

How did the FOA describe the typical focus of the R21 phase for imaging ligands?

For an imaging-ligand program, the first phase often implies radiochemistry development, demonstrating selectivity and brain-appropriate properties, and generating initial imaging evidence.

How did the FOA describe the typical focus of the R33 phase for imaging ligands?

The second phase was described as strengthening validation, optimizing imaging and kinetic modeling methods, and expanding feasibility testing toward broader utility in drug discovery or studies of CNS disease biology.

How can PET/SPECT imaging ligands support drug discovery according to the FOA?

Within drug discovery, the FOA noted that these ligands can help confirm that a drug reaches its intended target in the brain, measure target engagement and occupancy, and support dose selection or go/no-go decisions.

How can PET/SPECT imaging ligands support pathophysiological research in CNS disorders?

For pathophysiological research, the FOA described how imaging biomarkers can map where and when molecular targets are altered in CNS disorders, including receptors, transporters, enzymes, protein aggregates, and other molecular targets relevant to disease biology.

What kinds of molecular targets were explicitly mentioned as relevant for imaging?

The FOA mentioned receptors, transporters, enzymes, protein aggregates, and other molecular targets that may be altered in CNS disorders as examples of targets suitable for imaging biomarker development.

Who was eligible to apply?

Eligibility was broad and included many types of domestic and international organizations. Eligible applicants included public and private institutions of higher education, for-profit organizations (including small businesses), nonprofits with or without 501(c)(3) status, and multiple levels of government (state, county, city/township, and special districts), as well as public housing authorities and tribal governments or organizations.

Were mission-focused and minority-serving institutions included in eligibility?

Yes. The FOA explicitly included institutions and organizations such as Historically Black Colleges and Universities (HBCUs), Hispanic-serving institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian-serving institutions, and Asian American Native American Pacific Islander-serving institutions (AANAPISIs).

Were faith-based or community-based organizations eligible?

Yes. The opportunity explicitly included faith-based or community-based organizations among eligible applicants.

Were federal agencies eligible to apply?

The FOA indicated that eligible federal agencies were included among eligible organizations.

Were foreign organizations allowed to apply?

Yes. Foreign organizations and foreign institutions were allowed to apply, and foreign components of U.S. organizations were permitted under NIH policy definitions.

Was cost sharing or matching required?

No. The FOA stated there was no cost-sharing or matching requirement, meaning applicants were typically not required to provide institutional matching funds as a condition of award.

Which federal assistance listings (CFDA numbers) were associated with this FOA?

The opportunity aligned with CFDA numbers 93.242, 93.273, 93.279, and 93.866, spanning areas including mental health, alcohol research, drug abuse and addiction research, and aging research.

When was this funding opportunity posted, and what were the closing and archive dates?

The announcement was posted and created on March 25, 2013. The original and final closing date was May 7, 2016. It was archived on June 7, 2016.

Is this opportunity still open?

No. Based on the stated final closing date (May 7, 2016) and archive date (June 7, 2016), the FOA is no longer open for applications.

Where were applicants directed for full announcement details?

Applicants were directed to the NIH grants page for the full announcement details.

Who was listed as a contact for access or linking issues?

The NIH Office of Extramural Research (OER) webmaster contacts were provided for access or linking issues.

What was the overall intended impact of this FOA?

The opportunity was positioned to accelerate translation of promising PET and SPECT radioligands into tools usable in clinical and advanced research settings, supporting therapeutic development and deeper biological understanding of CNS disorders.