FAPI PET/CT Imaging in Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) (FAPI-ARVC)) (FAPI-ARVC)

Incremental Diagnostic and Prognostic Value of 68Ga-DOTA-SA-FAPI PET/CT Imaging in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease associated with fibrofatty myocardial replacement, ventricular arrhythmias, and an increased risk of sudden cardiac death. Although current diagnostic approaches, including the 2010 Task Force Criteria and the Padua criteria, improve recognition of the disease, early diagnosis remains challenging, particularly when structural abnormalities are subtle or absent on conventional imaging. Echocardiography and cardiac magnetic resonance imaging are central to evaluation, but their sensitivity for early or active fibrotic remodeling may be limited. This limitation may be particularly relevant in patients who are unable to undergo cardiac magnetic resonance imaging, in whom 68Ga-DOTA-SA-FAPI PET/CT may provide complementary diagnostic information.

This prospective single-group diagnostic imaging study aims to investigate the incremental value of protocol-specified 68Ga-DOTA-SA-FAPI PET/CT imaging in patients with ARVC. FAPI PET/CT is a novel molecular imaging method that targets activated fibroblasts and may allow non-invasive detection of active myocardial fibrosis.Fifteen adult patients with an established diagnosis of ARVC will undergo protocol-specified 68Ga-DOTA-SA-FAPI PET/CT imaging in addition to clinical evaluation, electrocardiography, echocardiography, and review of previously obtained cardiac magnetic resonance imaging findings. FAPI PET/CT findings will be compared with conventional diagnostic criteria and other clinical and imaging parameters, including previously available cardiac magnetic resonance imaging findings. Participants will also be followed clinically for 6 months after imaging to explore possible associations between FAPI uptake and short-term clinical outcomes, including arrhythmic events, ventricular function, and laboratory markers.

The study is expected to provide preliminary evidence on whether 68Ga-DOTA-SA-FAPI PET/CT may improve the detection of myocardial fibrosis and contribute to diagnostic assessment and risk stratification in ARVC. It may also help clarify the potential role of FAPI PET/CT in patients who are unable to undergo cardiac magnetic resonance imaging. The findings may support future larger prospective studies in this field.

Study Overview

• Status: Recruiting
• Conditions: Arrhythmogenic Right Ventricular Cardiomyopathy; Cardiac Magnetic Resonance Imaging; FAPI PET
• Intervention / Treatment: Diagnostic test: 68Ga-DOTA-SA-FAPI PET/CT

Detailed Description

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited myocardial disease characterized by progressive fibro-fatty replacement of the ventricular myocardium, predominantly involving the right ventricle, although left ventricular and biventricular forms are increasingly recognized. The disease is associated with ventricular arrhythmias, progressive ventricular dysfunction, heart failure, and sudden cardiac death. Because phenotypic expression is variable and may evolve over time, early diagnosis remains challenging, particularly in patients with subtle structural abnormalities or incomplete expression of conventional diagnostic criteria.

Current diagnostic evaluation relies on a multiparametric approach integrating electrocardiographic, arrhythmic, structural, functional, histopathological, and genetic findings. The revised 2010 Task Force Criteria improved standardization of diagnosis, and the Padua criteria further expanded the disease concept by incorporating left ventricular involvement. However, despite these advances, important limitations remain, especially in the early stages of disease, when conventional imaging may not adequately detect active myocardial remodeling.

Echocardiography and cardiac magnetic resonance imaging are central imaging modalities in ARVC. Echocardiography allows assessment of chamber dimensions, ventricular systolic function, and regional wall motion abnormalities, whereas cardiac magnetic resonance imaging provides more detailed characterization of ventricular volumes, function, and tissue abnormalities. Nevertheless, both techniques primarily reflect structural and functional consequences of disease and may be less sensitive for detecting early or biologically active fibrotic remodeling. This limitation is particularly relevant in a disease in which myocardial fibrosis is a major pathological substrate for electrical instability and arrhythmogenesis. It may also be especially important in patients who are unable to undergo cardiac magnetic resonance imaging because of contraindications or technical limitations. In such cases, 68Ga-DOTA-SA-FAPI PET/CT may provide complementary diagnostic information by enabling non-invasive assessment of active myocardial fibrotic remodeling.

Molecular imaging with fibroblast activation protein inhibitor positron emission tomography/computed tomography (FAPI PET/CT) has emerged as a promising non-invasive technique for visualizing activated fibroblasts in vivo. Fibroblast activation protein is overexpressed in activated fibroblasts involved in tissue remodeling and fibrogenesis. In cardiovascular disease, FAPI-based imaging has attracted growing interest as a potential marker of active fibrosis. In ARVC, where fibro-fatty myocardial replacement is a defining pathological feature, 68Ga-DOTA-SA-FAPI PET/CT may offer additional biological information beyond conventional imaging by identifying active fibroblast-related remodeling.

The present study is a prospective single-group diagnostic imaging study designed to evaluate the incremental value of protocol-specified 68Ga-DOTA-SA-FAPI PET/CT imaging in adult patients with ARVC. The central hypothesis is that FAPI PET/CT may improve the non-invasive assessment of myocardial fibrotic activity and provide complementary information to conventional multimodality evaluation.In particular, the study seeks to explore whether myocardial FAPI uptake is detectable in patients with ARVC and whether uptake patterns correlate with established clinical, electrocardiographic, echocardiographic, and previously obtained cardiac magnetic resonance findings. The study will also explore the potential usefulness of FAPI PET/CT in patients in whom cardiac magnetic resonance imaging is unavailable or cannot be performed.

The study will be conducted through collaboration between the Istanbul University-Cerrahpaşa Institute of Cardiology, Department of Cardiology, and the Istanbul Training and Research Hospital, Department of Nuclear Medicine. Fifteen adult patients with established ARVC who are under clinical follow-up will be enrolled prospectively. Following informed consent, participants will undergo comprehensive clinical evaluation together with electrocardiography, transthoracic echocardiography, review of previously obtained cardiac magnetic resonance imaging findings, and protocol-specified 68Ga-DOTA-SA-FAPI PET/CT imaging. No new cardiac magnetic resonance imaging will be performed as part of the study protocol.

The PET/CT imaging protocol includes intravenous administration of approximately 150-200 MBq of 68Ga-DOTA-SA-FAPI. No fasting or specific dietary preparation is required. After tracer injection, participants will rest during an uptake period of approximately 40-60 minutes. Imaging will then be performed using a hybrid PET/CT scanner. A low-dose CT acquisition will be obtained for attenuation correction and anatomical localization, followed by three-dimensional PET acquisition focused on the thoracic region for cardiac assessment. Images will be reconstructed according to standard institutional protocols using attenuation, scatter, and decay correction methods.

Image analysis will focus on the presence, localization, and pattern of myocardial FAPI uptake. Particular attention will be paid to uptake involving the right ventricular free wall, right ventricular outflow tract, interventricular septum, left ventricular myocardium, or biventricular distribution. Where technically feasible, semi-quantitative parameters such as standardized uptake values may also be recorded. These findings will be interpreted in relation to conventional imaging, including previously available cardiac magnetic resonance imaging, and clinical phenotype in order to assess the potential complementary role of FAPI PET/CT in ARVC characterization.

Participants will also undergo clinical follow-up for 6 months after PET/CT imaging. Follow-up data will include interval symptoms, arrhythmic events, clinical status, routine electrocardiographic findings, echocardiographic reassessment where available, and selected laboratory parameters obtained during standard care. This follow-up is intended to provide preliminary exploratory information regarding possible associations between baseline myocardial FAPI uptake and short-term clinical course.

As an exploratory pilot study, this project is primarily intended to generate early clinical evidence regarding the feasibility and potential usefulness of FAPI PET/CT in ARVC. The study is expected to clarify whether imaging of fibroblast activation may complement current structural and functional assessment, especially in cases where conventional modalities provide limited or equivocal information. It may also provide preliminary evidence regarding the potential role of FAPI PET/CT in the diagnostic evaluation of patients with ARVC who are unable to undergo cardiac magnetic resonance imaging, while also allowing comparison with previously obtained cardiac magnetic resonance data in patients with established ARVC. If myocardial uptake patterns appear biologically and clinically meaningful, the results may support the development of larger prospective studies investigating the diagnostic and prognostic role of FAPI PET/CT in arrhythmogenic cardiomyopathy.

Data will be collected and managed by the study investigators in accordance with institutional ethical standards. Study data will be coded and de-identified before analysis to protect participant confidentiality. Because this is an investigator-initiated academic study, analyses and interpretation will be performed independently by the research team. The results are expected to provide pilot data relevant to future multicentre research and to the broader investigation of molecular imaging biomarkers in inherited cardiomyopathies.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sukru Arslan, MD, Associate Professor; Phone Number: +90 555 623 2606; Email: sukru.arslan@iuc.edu.tr
• Study Contact Backup: Name: Sahra Asena Balcioglu, MD; Phone Number: +90 530 443 3766; Email: sahra.balcioglu@iuc.edu.tr

Study Locations

• Turkey (Türkiye)
  • Fatih
    • Istanbul, Fatih, Turkey (Türkiye)
      • Recruiting
      • Istanbul University-Cerrahpasa Institute of Cardiology
      • Contact: Sukru Arslan, MD, Associate Professor; Phone Number: +90 555 623 2606; Email: sukru.arslan@iuc.edu.tr
      • Contact: Sahra Asena Balcioglu, MD; Email: sahra.balcioglu@iuc.edu.tr

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Adults aged 18 years or older
• Established diagnosis of arrhythmogenic right ventricular cardiomyopathy according to the 2010 Revised Task Force Criteria and/or the Padua criteria
• Under active follow-up at the study center
• Ability to understand the study procedures and provide written informed consent

Exclusion Criteria:

• History of malignancy
• Severe renal impairment
• Severe hepatic impairment
• Pregnancy or breastfeeding
• Prior 68Ga-DOTA-SA-FAPI PET/CT imaging
• Inability or unwillingness to provide written informed consent
• Any medical, clinical, or logistical condition that, in the opinion of the investigators, could interfere with study participation, image interpretation, or completion of follow-up

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Adults With ARVC; Participants in this single-arm diagnostic imaging study will undergo protocol-specified 68Ga-DOTA-SA-FAPI PET/CT for assessment of myocardial fibroblast-related remodeling in arrhythmogenic right ventricular cardiomyopathy. All participants will also undergo clinical evaluation, 12-lead electrocardiography, transthoracic echocardiography, and review of previously obtained cardiac magnetic resonance imaging findings, followed by 6 months of protocol-defined clinical follow-up.

Diagnostic test: 68Ga-DOTA-SA-FAPI PET/CT; Protocol-specified 68Ga-DOTA-SA-FAPI positron emission tomography/computed tomography performed for assessment of myocardial fibroblast-related remodeling in patients with arrhythmogenic right ventricular cardiomyopathy. The imaging protocol includes intravenous administration of approximately 150-200 MBq of 68Ga-DOTA-SA-FAPI, an uptake period of 40-60 minutes, low-dose CT for attenuation correction and anatomical localization, and thoracic PET acquisition for cardiac assessment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Myocardial 68Ga-DOTA-SA-FAPI Uptake on PET/CT	Presence and distribution of myocardial 68Ga-DOTA-SA-FAPI uptake on PET/CT, assessed qualitatively and, where feasible, semi-quantitatively by maximum standardized uptake value (SUVmax).	At baseline (time of PET/CT imaging)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation Between Myocardial FAPI PET/CT Uptake and Fibrosis-Related Findings on Previously Obtained Cardiac Magnetic Resonance Imaging	Correlation between myocardial 68Ga-DOTA-SA-FAPI uptake on PET/CT and fibrosis-related abnormalities identified on previously obtained cardiac magnetic resonance imaging.	At baseline
Correlation Between Myocardial FAPI PET/CT Uptake and Right Ventricular Fractional Area Change on Transthoracic Echocardiography	Correlation between myocardial 68Ga-DOTA-SA-FAPI uptake on PET/CT and right ventricular fractional area change measured by transthoracic echocardiography.	At baseline
Incidence of Arrhythmic Events During 6-Month Follow-Up	Incidence of documented arrhythmic events during the 6 months following baseline 68Ga-DOTA-SA-FAPI PET/CT imaging.	Within 6 months after PET/CT imaging
Diagnostic Concordance Rate Between FAPI PET/CT and Previously Obtained Cardiac Magnetic Resonance Imaging	Concordance rate between myocardial abnormalities detected by 68Ga-DOTA-SA-FAPI PET/CT and fibrosis-related abnormalities identified on previously obtained cardiac magnetic resonance imaging.	At baseline
Diagnostic Concordance Between FAPI PET/CT and Established ARVC Evaluation	Exploratory comparison of myocardial 68Ga-DOTA-SA-FAPI PET/CT findings with established diagnostic evaluation based on clinical assessment and conventional multimodality imaging in ARVC.	At baseline
Correlation Between Myocardial FAPI PET/CT Uptake and Electrocardiographic Abnormalities on 12-Lead Electrocardiography	Correlation between myocardial 68Ga-DOTA-SA-FAPI uptake on PET/CT and predefined electrocardiographic abnormalities of ARVC on baseline 12-lead electrocardiography, including T-wave inversion, epsilon wave, and QRS prolongation.	At baseline

Collaborators and Investigators

• Sponsor: Istanbul University - Cerrahpasa

Publications and helpful links

General Publications

• Marcus FI, McKenna WJ, Sherrill D, Basso C, Bauce B, Bluemke DA, Calkins H, Corrado D, Cox MG, Daubert JP, Fontaine G, Gear K, Hauer R, Nava A, Picard MH, Protonotarios N, Saffitz JE, Sanborn DM, Steinberg JS, Tandri H, Thiene G, Towbin JA, Tsatsopoulou A, Wichter T, Zareba W. Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the task force criteria. Circulation. 2010 Apr 6;121(13):1533-41. doi: 10.1161/CIRCULATIONAHA.108.840827. Epub 2010 Feb 19.
• Protonotarios A, Wicks E, Ashworth M, Stephenson E, Guttmann O, Savvatis K, Sekhri N, Mohiddin SA, Syrris P, Menezes L, Elliott P. Prevalence of 18F-fluorodeoxyglucose positron emission tomography abnormalities in patients with arrhythmogenic right ventricular cardiomyopathy. Int J Cardiol. 2019 Jun 1;284:99-104. doi: 10.1016/j.ijcard.2018.10.083. Epub 2018 Oct 26.
• Mpanya D, Knuuti J, Saraste A. Gallium-68 fibroblast activation protein inhibitor positron emission tomography in cardiovascular disease. Front Nucl Med. 2023.
• Corrado D, Perazzolo Marra M, Zorzi A, Beffagna G, Cipriani A, Lazzari M, Migliore F, Pilichou K, Rampazzo A, Rigato I, Rizzo S, Thiene G, Anastasakis A, Asimaki A, Bucciarelli-Ducci C, Haugaa KH, Marchlinski FE, Mazzanti A, McKenna WJ, Pantazis A, Pelliccia A, Schmied C, Sharma S, Wichter T, Bauce B, Basso C. Diagnosis of arrhythmogenic cardiomyopathy: The Padua criteria. Int J Cardiol. 2020 Nov 15;319:106-114. doi: 10.1016/j.ijcard.2020.06.005. Epub 2020 Jun 16.
• Tessier R, Marteau L, Vivien M, Guyomarch B, Thollet A, Fellah I, Jamet B, Sebille JC, Eugene T, Serfaty JM, Probst V, Trochu JN, Toquet C, Warin-Fresse K, Piriou N. 18F-Fluorodeoxyglucose Positron Emission Tomography for the Detection of Myocardial Inflammation in Arrhythmogenic Left Ventricular Cardiomyopathy. Circ Cardiovasc Imaging. 2022 Jul;15(7):e014065. doi: 10.1161/CIRCIMAGING.122.014065. Epub 2022 Jun 30. No abstract available.
• Jorda P, Bosman LP, Gasperetti A, Mazzanti A, Gourraud JB, Davies B, Frederiksen TC, Weidmann ZM, Di Marco A, Roberts JD, MacIntyre C, Seifer C, Deliniere A, Alqarawi W, Kukavica D, Minois D, Trancuccio A, Arnaud M, Targetti M, Martino A, Oliviero G, Pipilas DC, Carbucicchio C, Compagnucci P, Dello Russo A, Olivotto I, Calo L, Lubitz SA, Cutler MJ, Chevalier P, Arbelo E, Priori SG, Healey JS, Calkins H, Casella M, Jensen HK, Tondo C, Tadros R, James CA, Krahn AD, Cadrin-Tourigny J. Arrhythmic risk prediction in arrhythmogenic right ventricular cardiomyopathy: external validation of the arrhythmogenic right ventricular cardiomyopathy risk calculator. Eur Heart J. 2022 Aug 21;43(32):3041-3052. doi: 10.1093/eurheartj/ehac289.
• Malik N, Mukherjee M, Wu KC, Zimmerman SL, Zhan J, Calkins H, James CA, Gilotra NA, Sheikh FH, Tandri H, Kutty S, Hays AG. Multimodality Imaging in Arrhythmogenic Right Ventricular Cardiomyopathy. Circ Cardiovasc Imaging. 2022 Feb;15(2):e013725. doi: 10.1161/CIRCIMAGING.121.013725. Epub 2022 Feb 11.

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2025
• Primary Completion (Estimated): August 25, 2026
• Study Completion (Estimated): October 26, 2026

Study Registration Dates

• First Submitted: April 22, 2026
• First Submitted That Met QC Criteria: April 30, 2026
• First Posted (Actual): May 4, 2026

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 30, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Myocardial Fibrosis; Cardiac Magnetic Resonance Imaging; Fibroblast Activation Protein; Positron Emission Tomography Computed Tomography; Arrhythmogenic Right Ventricular Cardiomyopathy; Molecular Cardiac Imaging; Sudden Cardiac Death Risk Stratification; Inherited Cardiomyopathy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Cardiomyopathies; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Defects, Congenital; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Arrhythmogenic Right Ventricular Dysplasia
• Other Study ID Numbers: 2025/1410112IUC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Individual participant data sharing has not yet been determined. Any future data sharing will be considered in accordance with institutional policies, ethics committee approval, participant confidentiality, and applicable data protection regulations.

Drug and device information, study documents

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