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

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.

• INCLUSION CRITERIA

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

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Participant >=18 years old
• Has a specific diagnosis of a cardiopulmonary and/or vascular disease that puts them at risk of developing or having developed tissue fibrosis.
• Has undergone prior imaging of lungs, heart, and/or vasculature with chest CT
• Able to lie on the PET/CT scanner for imaging up to 45 minutes.
• 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.
• 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.
• 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:

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to 18F-FAPI-74 or other agents used in the study.
• Uncontrolled intercurrent illness, factors, or social situations that would limit compliance with study requirements
• Pregnancy or lactation
• 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.
• Subjects with severe claustrophobia unresponsive to oral anxiolytics.
• Subjects weighing > 350 lbs (weight limit for PET scanner table), or unable to fit within the imaging gantry