Labeling galectin-3 for the assessment of myocardial infarction in rats.

Teresa Arias,Carlos Pérez-Medina,Artiom Petrov,Zahi A Fayad,Hans De Haas,Roger J Hajjar,Jiqiu Chen,Gustav J Strijkers,Jagat Narula,Valentín Fuster

doi:10.1186/s13550-014-0075-x

Abstract

BackgroundGalectin-3 is a ß-galactoside-binding lectin expressed in most of tissues in normal conditions and overexpressed in myocardium from early stages of heart failure (HF). It is an established biomarker associated with extracellular matrix (ECM) turnover during myocardial remodeling. The aim of this study is to test the ability of 123I-galectin-3 (IG3) to assess cardiac remodeling in a model of myocardial infarction (MI) using imaging techniques.MethodsRecombinant galectin-3 was labeled with iodine-123 and in vitro binding assays were conducted to test 123I-galectin-3 ability to bind to ECM targets. For in vivo studies, a rat model of induced-MI was used. Animals were subjected to magnetic resonance and micro-SPETC/micro-CT imaging two (2 W-MI) or four (4 W-MI) weeks after MI. Sham rats were used as controls. Pharmacokinetic, biodistribution, and histological studies were also performed after intravenous administration of IG3.ResultsIn vitro studies revealed that IG3 shows higher binding affinity (measured as counts per minute, cpm) (p < 0.05) to laminin (2.45 ± 1.67 cpm), fibronectin (4.72 ± 1.95 cpm), and collagen type I (1.88 ± 0.53 cpm) compared to bovine serum albumin (BSA) (0.88 ± 0.31 cpm). Myocardial quantitative IG3 uptake (%ID/g) was higher (p < 0.01) in the infarct of 2 W-MI rats (0.15 ± 0.04%) compared to control (0.05 ± 0.03%). IG3 infarct uptake correlates with the extent of scar (rs = 1, p = 0.017). Total collagen deposition in the infarct (percentage area) was higher (p < 0.0001) at 2 W-MI (24.2 ± 5.1%) and 4 W-MI (30.4 ± 7.5%) compared to control (1.9 ± 1.1%). However, thick collagen content in the infarct (square micrometer stained) was higher at 4 W-MI (20.5 ± 11.2 μm2) compared to control (4.7 ± 2.0 μm2, p < 0.001) and 2 W-MI (10.6 ± 5.1 μm2, p < 0.05).ConclusionsThis study shows, although preliminary, enough data to consider IG3 as a potential contrast agent for imaging of myocardial interstitial changes in rats after MI. Labeling strategies need to be sought to improve in vivo IG3 imaging, and if proven, galectin-3 might be used as an imaging tool for the assessment and treatment of MI patients.

Highlights

Galectin-3 is a ß-galactoside-binding lectin expressed in most of tissues in normal conditions and overexpressed in myocardium from early stages of heart failure (HF)
Because binding sites are excessively expressed in extracellular matrix (ECM) and on proliferating myofibroblasts, we investigated the suitability of iodine-123-labeled galectin-3 (IG3) as a single-photon emission computed tomography (SPECT) probe for myocardial remodeling imaging in a rodent model of post-myocardial infarction (MI) HF
Solid-phase radiolabeling binding assay In vitro solid-phase radiolabeling binding assays were carried out to check whether labeling altered the galectin-3 structure and to confirm the ability of IG3 to bind to ECM targets

Summary

Introduction

Galectin-3 is a ß-galactoside-binding lectin expressed in most of tissues in normal conditions and overexpressed in myocardium from early stages of heart failure (HF). It is an established biomarker associated with extracellular matrix (ECM) turnover during myocardial remodeling. Galectin-3 is present in most tissues in normal conditions and overexpressed in myocardium from the early stages of HF [12], especially post-myocardial infarction (MI) [13,14]. The serum levels of galectin-3 in HF patients are significantly correlated with other established biomarkers of ECM turnover such as type III aminoterminal propeptide of procollagen (PIIINP), matrix metalloprotease-2 (MMP-2), and tissue inhibitor of metalloprotease-1 (TIMP-1), as with the New York Heart Association (NYHA) functional class [18]

Objectives

Methods

Results

Discussion

Conclusion