Imaging of cardiac fibroblast activation in a patient after acute myocardial infarction using 68Ga-FAPI-04

doi:10.1007/s12350-021-02603-z

Journal of Nuclear Cardiology

Volume 29, Issue 5, October 2022, Pages 2254-2261

https://doi.org/10.1007/s12350-021-02603-z Get rights and content

Abstract

Our previous study has demonstrated the feasibility of noninvasive imaging of fibroblast activation protein (FAP)-expression after myocardial infarction (MI) in MI-territory in a rat model with ⁶⁸Ga-FAPI-04-PET. In the current extended clinical case, we sought to delineate cardiac uptake of ⁶⁸Ga-FAPI-04 in a patient after MI with clinical indication for the evidence of fibroblast activation. Carcinoma patients without cardiac disease underwent ⁶⁸Ga-FAPI-04-PET/CT as control. The patient with one-vessel disease underwent dynamic ⁶⁸Ga-FAPI-04-cardiac-PET/CMR for 60 minutes. Correlation of cardiac ⁶⁸Ga-FAPI-04 uptake with clinical findings, ECG, echocardiography, coronary-arteriography and enhanced cardiac-MRI with T1 MOLLI and ECV mapping were performed. No uptake was found in normal myocardium and in mature scar. A focal intense ⁶⁸Ga-FAPI-04 uptake with continuous wash-out in the infarct territory of coronary occlusion correlating with T1 and ECV mapping was observed. The uptake of ⁶⁸Ga-FAPI-04 extends beyond the actual infarcted area and overestimates the infarct size as confirmed by follow-up CMR.

Introduction

Following myocardial infarction (MI), an orchestrated inflammatory response and reparative pathways are initiated, aiming to produce a robust and collagen-rich scar.¹^,² The phenotype conversion of cardiac fibroblasts to their overly active counterparts, myofibroblasts, is the critical event in cardiac remodeling.³^,⁴ Post-MI, a high abundance of extracellular matrix proteins is synthesized by myofibroblasts to replace myocyte loss and form a reparative scar. A balanced turnover of extracellular matrix via extracellular matrix synthesis by activated fibroblasts and degradation by matrix metalloproteinases is crucial for proper scar formation.⁴ The excessively increased activity of the fibroblasts resulting in excessive fibrosis within the myocardium is associated with poor patient prognosis. A diagnostic strategy targeted at detecting active ongoing fibrosis may provide critical insights into pathogenesis of heart failure. In addition, early detection of cardiac remodeling and fibrosis may be essential to prevent development of apparent heart failure.

The serine protease fibroblast activation protein (FAP) is a membrane-anchored enzyme which is specifically expressed in fibroblasts activated to differentiate to (proto-)myofibroblasts, but not in dormant fibroblasts or mature fibrocytes.⁵ ⁶⁸Gallium-labeled FAP-inhibitor (FAPI) compound 04 (⁶⁸Ga-FAPI-04) was initially introduced for PET imaging of cancer-associated fibroblasts.⁶ In our previous work, we demonstrated that image derived FAP expression after MI in a rat model allowed noninvasive PET imaging of activated fibroblasts.⁷

Further retrospective evaluations of cardiac FAPI distribution in a heterogeneous patient population with metastasized cancer associated with preexisting coronary artery disease, cardiovascular risk factors or metabolic disease were reported.⁸^,⁹ However, ⁶⁸Ga-FAPI-04-PET investigations in patients after MI have not been reported yet. For this case presentation, we retrospectively evaluated fibroblast activation in a patient after MI und carcinoma patients without cardiac disease.

Section snippets

Case Presentation

All examinations had clinical indications and complied to the conditions of the updated Declaration of Helsinki (Section 37, unproven interventions in clinical practice) and the German Pharmaceutical Law (Section 13, 2b). In the controls, the indications for ⁶⁸Ga-FAPI-04-PET/CT was the possible compassionate use of ¹⁷⁷Lu-FAPI-radiotherapy¹⁰ and staging. In a patient after MI, the indications for ⁶⁸Ga-FAPI-04-PET/MR was the compassionate use for chimeric antigen receptor T-cell-therapy¹¹ of

Discussion

In the present retrospective analysis of cardiac ⁶⁸Ga-FAPI-04 uptake in patients with no prior history of cardiac disease and in a patient after acute MI, we found substantial different results (Figures 1A, 2A). In patients without history of cardiac disease, the myocardium showed a homogenous tracer uptake similar to the blood pool activity (Figure 1). Whereas, in the patient with acute MI, a focal intense uptake of ⁶⁸Ga-FAPI-04 was registered in the infarct territory of the occluded coronary

Conclusion

As shown in this case of a patient after STEMI, the enhanced FAP activation in acutely injured myocardium was identified und visualized with ⁶⁸Ga-FAPI-04-PET. Noninvasive assessment of activated fibroblasts may provide unique opportunities to identify early manifestation of cardiac remodeling amenable to preventive intervention.

Funding

Open Access funding enabled and organized by Projekt DEAL. Alberto Villagran Asiares received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Grant Agreement No 764458.

Disclosure

No conflict of interest.

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Case Presentation CornerImaging of cardiac fibroblast activation in a patient after acute myocardial infarction using 68Ga-FAPI-04

Abstract

Introduction

Section snippets

Case Presentation

Discussion

Conclusion

Funding

Disclosure

J Am Coll Cardiol Basic Trans Sci

J Am Coll Cardiol

Mol Ther

J Am Coll Cardiol

Cardiology

Regulation of the inflammatory response in cardiac repair

Circ Res

The biological basis for cardiac repair after myocardial infarction—From inflammation to fibrosis

Circ Res

Defining the cardiac fibroblast

Circ J

Case Presentation Corner
Imaging of cardiac fibroblast activation in a patient after acute myocardial infarction using ⁶⁸Ga-FAPI-04