Fibrotic Disease Activity in Cardiopulmonary Disorders Using 18F-Fibroblast Activation Protein Inhibitor (18F-FAPI-74) PET/CT Imaging

Evaluation of Fibrotic Disease Activity in Cardiopulmonary Disorders Using 18F-Fibroblast Activation Protein Inhibitor (18F-FAPI-74 PET/CT Imaging)

Background:

Injury or diseases of the heart and lung can sometimes cause scar tissue (fibrosis) to build up in those organs. Current imaging scans can see this scar tissue once it has formed, but researchers want to find a way to detect the fibrosis in its earliest stages, while there might still be time to prevent serious damage. A new tracer (a radioactive substance injected during imaging scans) may be able to help.

Objective:

To test a new tracer (18F-FAPI-74) during imaging scans in people with heart or lung disease.

Eligibility:

People aged 18 years and older with lung or heart disease that may cause scarring in those organs.

Design:

Participants will have 6 clinic visits over 2 years.

Participants will be screened: They will have blood tests and tests of their heart and lung function. Those with heart disease will have a magnetic resonance imaging (MRI) scan of the heart.

The study tracer will be used with positron emission tomography (PET)/computed tomography (CT) scans. The study tracer will be injected into a vein in the arm. Participants will lie on a padded bed that slides through a donut-shaped machine.

Participants will have scans with the study tracer 2 times, 8 to 12 months apart. They will also have standard CT scans and blood tests during these visits. They will also have blood tests at 3 and 6 months between these visits.

Participants will have a follow-up visit after 18 to 24 months. The study scans, MRI and standard CT scans, and lung function tests may be repeated.

Study Overview

• Status: Not yet recruiting
• Conditions: Cardiovascular Diseases; Pulmonary Arterial Hypertension; Acute Lung Injury; Interstitial Lung Disease; Allogeneic Stem Cell Transplantation; Lung Allograft Transplantation
• Intervention / Treatment: Diagnostic test: 18F-FAPI-74 PET/CT Imaging; Drug: [18F]FAPI-74

Detailed Description

Study Description:

Fibroblast activation protein-targeted PET detects activated fibroblasts in a range of inflammatory and fibrosing cardiovascular and pulmonary disorders. It is a sensitive and quantifiable intervention to diagnose and monitor the natural history of cardiopulmonary disorders and/or the effects of antifibrotic interventions.

Objectives:

Primary objective:

To compare 18F-FAPI-74 PET/CT to standard of care (SOC) imaging (18F-FDG-PET/CT, non-contrast chest CT, and cardiac MRI for heart cohort) to detect fibrosis.

Secondary objective:

To compare the ability of 18F-FAPI-74 PET/CT imaging to assess the natural history or treatment responses with standard of care imaging in cardiopulmonary diseases associated with fibrosis.

Exploratory objectives:

To use high density proteomic, transcriptomic, and metagenomic analysis of specimens from lung and/or blood to define associated mechanisms and biomarkers of active fibrosis with the visualization and quantification of FAP expression.

Endpoints:

Primary:

Compare 18F-FAPI-74 PET/CT to standard of care (SOC) imaging with 18F-FDG-PET/CT (with the rate of concordance defined as a quantitative measure of the abnormal lung parenchyma detected in both the FAPI and FDG PET scans ranging from 0 to 100%) and cardiac MRI for heart cohort for the development of pulmonary or cardiovascular fibrosis at baseline These findings will be evaluated separately in six different at-risk cohorts (allogeneic stem cell transplant, lung allograft transplant, interstitial lung disease, acute lung injury, pulmonary arterial hypertension, and cardiovascular disease).

Secondary:

Compare the ability of 18F-FAPI-74 PET/CT imaging to assess the progression of fibrosis or treatment response compared to SOC imaging. The magnitude of change in 18F-FAPI-74 PET/CT uptake (SUVmax and mean/median) between scans one and two will be compared. Comparisons of the quantitative chest CT abnormalities will be compared to both 18F-FAPI-74 PET/CT and 18F-FDGPET/CT scans. These findings will be evaluated separately in six different at-risk cohorts (allogeneic stem cell transplant, lung allograft transplant, interstitial lung disease, acute lung injury, pulmonary arterial hypertension, and cardiovascular disease). Comparison of 18F-FAPI-74 PET/CT to standard of care (SOC) imaging at up to 12 months after the initial scan at baseline and change from the baseline.

Exploratory:

To use high density proteomic, transcriptomic, and metagenomic analysis of specimens from lung and/or blood to define associated biomarkers and mechanisms of active fibrosis with the visualization and quantitation of FAP expression.

• Study Type: Interventional
• Enrollment (Estimated): 210
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Gloria Y Pastor, R.N.; Phone Number: (301) 402-3484; Email: gloria.pastor@nih.gov
• Study Contact Backup: Name: Anthony F Suffredini, M.D.; Phone Number: (301) 496-9320; Email: asuffredini@mail.nih.gov

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center
      • Contact: NIH Clinical Center Office of Patient Recruitment (OPR); Phone Number: TTY dial 711 800-411-1222; Email: ccopr@nih.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

• INCLUSION CRITERIA

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. Provision of signed and dated informed consent form
2. Stated willingness to comply with all study procedures and availability for the duration of the study
3. Participant >=18 years old
4. Has a specific diagnosis of a cardiopulmonary and/or vascular disease that puts them at risk of developing or having developed tissue fibrosis.
5. Has undergone prior imaging of lungs, heart, and/or vasculature with chest CT
6. Able to lie on the PET/CT scanner for imaging up to 45 minutes.
7. For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 4 weeks after the end of FAPI-PET/CT or the FDG PET/CT scan.
8. For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner during study participation and for an additional 4 weeks after the end of FAPI-PET/CT or the FDG PET/CT scan.
9. Ability of subject to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA

An individual who meets any of the following criteria will be excluded from participation in this study:

1. History of allergic reactions attributed to compounds of similar chemical or biologic composition to 18F-FAPI-74 or other agents used in the study.
2. Uncontrolled intercurrent illness, factors, or social situations that would limit compliance with study requirements
3. Pregnancy or lactation
4. Women able to become pregnant or men actively trying to father a child and are unwilling to use an effective form of birth control during the study and 4 weeks after the last 18F-FAPI-74 PET/CT scan or the FDG PET/CT scan.
5. Subjects with severe claustrophobia unresponsive to oral anxiolytics.
6. Subjects weighing > 350 lbs (weight limit for PET scanner table), or unable to fit within the imaging gantry

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Acute lung injury; Acute lung injury undergoing FAPI/PET/CT	Diagnostic test: 18F-FAPI-74 PET/CT Imaging; Fibroblast activation protein-targeted PET detects activated fibroblasts in a range of inflammatory and fibrosing cardiovascular and pulmonary disorders. It is a sensitive and quantifiable intervention to diagnose and monitor the natural history of cardiopulmonary disorders and/or the effects of antifibrotic interventions.; Drug: [18F]FAPI-74; Participants will undergo baseline diagnostic 18F-FAPI-74 PET/CT in addition to standard of care imaging (non-contrast chest CT and 18FFDG- PET/CT, cardiac MRI for heart cohort). A follow-up 18F-FAPI- 74 PET/CT with SOC imaging will be performed at 8 to 12 months after the initial scan to assess progression and or the effects of therapies.
Other: Allogeneic stem cell transplantation; Allogeneic stem cell transplantation undergoing FAPI/PET/CT	Diagnostic test: 18F-FAPI-74 PET/CT Imaging; Fibroblast activation protein-targeted PET detects activated fibroblasts in a range of inflammatory and fibrosing cardiovascular and pulmonary disorders. It is a sensitive and quantifiable intervention to diagnose and monitor the natural history of cardiopulmonary disorders and/or the effects of antifibrotic interventions.; Drug: [18F]FAPI-74; Participants will undergo baseline diagnostic 18F-FAPI-74 PET/CT in addition to standard of care imaging (non-contrast chest CT and 18FFDG- PET/CT, cardiac MRI for heart cohort). A follow-up 18F-FAPI- 74 PET/CT with SOC imaging will be performed at 8 to 12 months after the initial scan to assess progression and or the effects of therapies.
Other: Cardiovascular diseases; Cardiovascular diseases undergoing FAPI/PET/CT	Diagnostic test: 18F-FAPI-74 PET/CT Imaging; Fibroblast activation protein-targeted PET detects activated fibroblasts in a range of inflammatory and fibrosing cardiovascular and pulmonary disorders. It is a sensitive and quantifiable intervention to diagnose and monitor the natural history of cardiopulmonary disorders and/or the effects of antifibrotic interventions.; Drug: [18F]FAPI-74; Participants will undergo baseline diagnostic 18F-FAPI-74 PET/CT in addition to standard of care imaging (non-contrast chest CT and 18FFDG- PET/CT, cardiac MRI for heart cohort). A follow-up 18F-FAPI- 74 PET/CT with SOC imaging will be performed at 8 to 12 months after the initial scan to assess progression and or the effects of therapies.
Other: Interstitial lung disease; Interstitial lung disease undergoing FAPI/PET/CT	Diagnostic test: 18F-FAPI-74 PET/CT Imaging; Fibroblast activation protein-targeted PET detects activated fibroblasts in a range of inflammatory and fibrosing cardiovascular and pulmonary disorders. It is a sensitive and quantifiable intervention to diagnose and monitor the natural history of cardiopulmonary disorders and/or the effects of antifibrotic interventions.; Drug: [18F]FAPI-74; Participants will undergo baseline diagnostic 18F-FAPI-74 PET/CT in addition to standard of care imaging (non-contrast chest CT and 18FFDG- PET/CT, cardiac MRI for heart cohort). A follow-up 18F-FAPI- 74 PET/CT with SOC imaging will be performed at 8 to 12 months after the initial scan to assess progression and or the effects of therapies.
Other: Lung allograft transplantation; Lung allograft transplantation undergoing FAPI/PET/CT	Diagnostic test: 18F-FAPI-74 PET/CT Imaging; Fibroblast activation protein-targeted PET detects activated fibroblasts in a range of inflammatory and fibrosing cardiovascular and pulmonary disorders. It is a sensitive and quantifiable intervention to diagnose and monitor the natural history of cardiopulmonary disorders and/or the effects of antifibrotic interventions.; Drug: [18F]FAPI-74; Participants will undergo baseline diagnostic 18F-FAPI-74 PET/CT in addition to standard of care imaging (non-contrast chest CT and 18FFDG- PET/CT, cardiac MRI for heart cohort). A follow-up 18F-FAPI- 74 PET/CT with SOC imaging will be performed at 8 to 12 months after the initial scan to assess progression and or the effects of therapies.
Other: Pulmonary arterial hypertension; Pulmonary arterial hypertension undergoing FAPI/PET/CT	Diagnostic test: 18F-FAPI-74 PET/CT Imaging; Fibroblast activation protein-targeted PET detects activated fibroblasts in a range of inflammatory and fibrosing cardiovascular and pulmonary disorders. It is a sensitive and quantifiable intervention to diagnose and monitor the natural history of cardiopulmonary disorders and/or the effects of antifibrotic interventions.; Drug: [18F]FAPI-74; Participants will undergo baseline diagnostic 18F-FAPI-74 PET/CT in addition to standard of care imaging (non-contrast chest CT and 18FFDG- PET/CT, cardiac MRI for heart cohort). A follow-up 18F-FAPI- 74 PET/CT with SOC imaging will be performed at 8 to 12 months after the initial scan to assess progression and or the effects of therapies.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To compare 18F-FAPI-74 PET/CT to standard of care imaging (non-contrast chest CT and 18F-FDG-PET/CT, cardiac MRI for heart cohort) to detect fibrosis.	Compare 18F-FAPI-74 PET/CT to standard of care (SOC) imaging with 18F-FDG-PET/CT with the rate of concordance defined as a quantitative measure of the abnormal lung parenchyma detected in both the FAPI and FDG PET scans ranging from 0 to 100% and cardiac MRI for heart cohort for the development of pulmonary or cardiovascular fibrosis at baseline.	Initial scan, Baseline, 8-12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To compare the ability of 18F-FAPI-74 PET/CT imaging to assess the natural history or treatment responses with standard of care imaging in cardiopulmonary diseases associated with fibrosis	Compare the ability of 18F-FAPI-74 PET/CT imaging to assess the progression of fibrosis or treatment response compared to SOC imaging. The magnitude of change in 18F-FAPI-74 PET/CT uptake (SUVmax and mean/median) between scans one and two will be compared. Comparisons of the quantitative chest CT abnormalities will be compared to both 18F-FAPI-74 PET/CT and 18F-FDG-PET/CT scans. These findings will be evaluated separately in six different at-risk cohorts (allogeneic stem cell transplant, lung allograft transplant, interstitial lung disease, acute lung injury, pulmonary arterial hypertension, and cardiovascular disease).	Baseline, 8-12 months
To compare the ability of 18F-FAPI-74 PET/CT imaging to assess the natural history or treatment responses with standard of care imaging in cardiopulmonary diseases associated with fibrosis	Comparison of 18F-FAPI-74 PET/CT to standard of care (SOC) imaging at up to 12 months after the initial scan at baseline and change from the baseline.	Baseline, 8-12 months

Collaborators and Investigators

• Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Anthony F Suffredini, M.D., National Heart, Lung, and Blood Institute (NHLBI)

Publications and helpful links

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Estimated): June 8, 2026
• Primary Completion (Estimated): May 26, 2031
• Study Completion (Estimated): May 26, 2033

Study Registration Dates

• First Submitted: May 28, 2026
• First Submitted That Met QC Criteria: May 28, 2026
• First Posted (Actual): May 29, 2026

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: June 2, 2026
• Last Verified: May 27, 2026

More Information

Terms related to this study

• Keywords: Fibroblast activation protein (FAP) FAPI/PET; Fibrotic Disease Activity
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Injury; Hypertension, Pulmonary; Pulmonary Arterial Hypertension; Cardiovascular Diseases; Lung Diseases, Interstitial; Acute Lung Injury
• Other Study ID Numbers: 10002534; 002534-H

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: refer to the DMSP
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No