Quantitative visualization of myocardial ischemia-reperfusion-induced cardiac lesions via ferroptosis magnetic particle imaging

Abstract

Myocardial ischemia-reperfusion (MI/R) injury is a complication in vascular reperfusion therapy for MI, occurring in approximately 60% of patients. Ferroptosis is an important process in the development of MI/R cardiac lesions. Transferrin receptor 1 (TfR1), a marker of ferroptosis, corresponds to the changes in MI/R cardiac lesions and is expected to be a biomarker for detecting MI/R-induced ferroptosis. However, the noninvasive in vivo visualization of ferroptosis in MI/R is a big challenge. Thus, this study aimed to develop a novel multimodal imaging platform to identify markers of MI/R cardiac lesions in vivo through targeting TfR1. Methods: Magnetic particle imaging (MPI) modality for ferroptosis based on superparamagnetic cubic-iron oxide nanoparticles (SCIO NPs), named feMPI, has been developed. FeMPI used TfR1 as a typical biomarker. The feMPI probe (SCIO-ICG-CRT-CPPs NPs, CCI NPs) consists of SCIO NPs, TfR1-targeting peptides (CRT), cell-penetrating peptides (CPPs), and indocyanine green (ICG). The specificity and sensitivity of CCI NPs in the MI/R mouse model were evaluated by MPI, magnetic resonance imaging (MRI), and near-infrared (NIR) fluorescent imaging. Results: The intensity of the MPI signal correlates linearly with the percentage of infarct area in MI/R stained by TTC, enabling a quantitative assessment of the extent of cardiac lesions. Notably, these findings are consistent with the standard clinical biochemical indicators in MI/R within the first 24 h. FeMPI detects cardiac injury approximately 48 h prior to the current clinical imaging detection methods of MI/R. Conclusion:The feMPI strategy can be a powerful tool for studying the process of MI/R-induced ferroptosis in vivo, providing clues for molecular imaging and drug development of ferroptosis-related treatments.

Enhanced TfR1 Recognition of Myocardial Injury after Acute Myocardial Infarction with Cardiac Fibrosis via Pre-Degrading Excess Fibrotic Collagen

“…Therefore, we hypothesized that molecular imaging targeting TfR1 may be useful for accurately detecting MI injury. At present, there are few reports on molecular imaging in vivo detection methods for ferroptosis, which weakens the rationality and enthusiasm of developing drugs for the treatment of ferroptosis [26][27][28]. Therefore, the present study further proposes that TfR1 overexpression can be used as a biomarker of ferroptosis considering iron homeostasis in healthy participants.…”

Elucidating Iron Metabolism through Molecular Imaging

“…The increase in iron is associated with the pathophysiology of I/R injury in various organs, including the heart [38]. Notably, recent research [102] has showcased an innovative magnetic particle imaging technique-ferroptosis magnetic particle imaging (feMPI)-which employs feMPI probes (mainly composed of superparamagnetic iron oxide nanoparticles (Scio NPs), indocyanine green (ICG), TfR 1-targeting peptide (CRT) 24, and cell-penetrating peptide (CPP)), specifically targeting transferrin receptor 1 (TfR1). This method enables precise and real-time in vivo localization and identification of cardiac injury markers caused by myocardial ischemia/reperfusion (MI/R), offering a novel molecular imaging strategy for early diagnosis and treatment of heart diseases.…”