Spatial FAP Expression as Detected by ⁶⁸ Ga-FAPI-46 Identifies Myofibroblasts Beyond the Infarct Scar After Reperfusion.

IF 3 4区医学 Q2 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

Molecular Imaging and Biology Pub Date : 2025-03-03 DOI:10.1007/s11307-025-01994-6

Annika Hess, Alexandra Renko, Andreas Schäfer, Mira Jung, Daniela Fraccarollo, Jan D Schmitto, Johanna Diekmann, Thomas Thum, Frank M Bengel, Johann Bauersachs, James T Thackeray, Jochen Tillmanns

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引用次数: 0

Abstract

Purpose: Myocardial infarction (MI) triggers complex cellular responses essential for tissue repair and remodeling, including myofibroblast activation. Fibroblast activation protein alpha (FAP) identifies activated myofibroblasts post-MI, however its spatial distribution relative to the scar and area at risk (AAR) is unclear. Non-invasive FAP-imaging with PET radiotracer ⁶⁸ Ga-FAPI-46 shows uptake beyond the infarct scar. We therefore aimed to characterize FAP expression in the AAR using a myocardial ischemia-reperfusion (MI/R) model in mice.

Procedures: We induced MI/R in male C57BL/6N mice. The AAR was identified by in vivo lectin staining, and expression of FAP, CD68, and hypoxic tissues were measured using immunohistochemistry. Spatial FAP was further interrogated by ⁶⁸ Ga-FAPI-46 in mice by autoradiography and humans by PET. Additionally, human cardiac tissues from acute MI patients were examined for fibroblasts and inflammatory cells by expression of FAP, CD13, and α-smooth muscle actin.

Results: FAP expression peaked three days post-MI/R predominantly within the AAR (p < 0.05 vs. d0). Consistent between murine models and human tissues, FAP⁺ myofibroblasts accumulated within the infarct scar and borderzone, occasionally extending into non-ischemic myocardium. CD68⁺ macrophages peaked similarly at three days post-MI/R (p < 0.05 vs. d0). FAP expression weakly correlated with CD68 but not with extent of ischemic or hypoxic territory post-MI/R. FAP imaging in mice and humans revealed aligned non-uniform ⁶⁸ Ga-FAPI-46 uptake extending from the infarct scar into surviving myocardium after MI.

Conclusions: Our findings demonstrate a distinct FAP expression pattern post-MI/R. The alignment of ex vivo ⁶⁸ Ga-FAPI-46 signal with myofibroblasts in the AAR supports its identification of a unique substrate in myocardial injury complementing other non-invasive imaging measurements of perfusion, viability and fibrosis.

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来源期刊

Molecular Imaging and Biology 医学-核医学

CiteScore

6.90

自引率

3.20%

发文量

审稿时长

3 months

期刊介绍： Molecular Imaging and Biology (MIB) invites original contributions (research articles, review articles, commentaries, etc.) on the utilization of molecular imaging (i.e., nuclear imaging, optical imaging, autoradiography and pathology, MRI, MPI, ultrasound imaging, radiomics/genomics etc.) to investigate questions related to biology and health. The objective of MIB is to provide a forum to the discovery of molecular mechanisms of disease through the use of imaging techniques. We aim to investigate the biological nature of disease in patients and establish new molecular imaging diagnostic and therapy procedures. Some areas that are covered are: Preclinical and clinical imaging of macromolecular targets (e.g., genes, receptors, enzymes) involved in significant biological processes. The design, characterization, and study of new molecular imaging probes and contrast agents for the functional interrogation of macromolecular targets. Development and evaluation of imaging systems including instrumentation, image reconstruction algorithms, image analysis, and display. Development of molecular assay approaches leading to quantification of the biological information obtained in molecular imaging. Study of in vivo animal models of disease for the development of new molecular diagnostics and therapeutics. Extension of in vitro and in vivo discoveries using disease models, into well designed clinical research investigations. Clinical molecular imaging involving clinical investigations, clinical trials and medical management or cost-effectiveness studies.