Myocardial remodeling is one of the principal characteristics of heart failure (HF) [
1],[
2], which remains a major cause of morbidity and mortality, both in the high and low income countries [
3]. Myocardial remodeling is the result of alterations in the cellular and subcellular elements of cardiomyocyte and non-cardiomyocyte components of the myocardium and results primarily from the excessive accumulation of collagen in interstitial and perivascular regions [
1]. Initially, the alterations associated with remodeling appear to compensate for the damage whereas its persistence over time causes progressive adverse remodeling and results in HF regardless of the etiology [
4]. Given that the progressive myocardial fibrosis produces abnormalities that affect cardiac function and electrical activity of the heart and plays an important role in the development of HF, it is of great importance to develop novel circulating biomarkers and noninvasive imaging strategies that accurately define the evolution of myocardial fibrosis. In this context, galectin-3 has been proposed as a peripheral biomarker that has been related with inflammation and fibrosis underlying adverse cardiac remodeling [
5]-[
8]. Galectin-3 is a 29- to 35-KDa ß-galactoside-binding animal lectin [
9] expressed by activated macrophages, eosinophils, neutrophils, and mast cells [
10]. There are many ligands for galectin-3, some of them are extracellular matrix components like laminin or fibronectin [
9]-[
11]. 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]. Galectin-3 induces myocardial fibroblast proliferation, collagen deposition, and ventricular dysfunction in rats [
15]; galectin-3 binding sites are abundantly expressed on rat cardiac fibroblasts and within the extracellular matrix (ECM) [
15]. Therefore, galectin-3 has been proposed as a biomarker associated with ECM turnover in the setting of HF [
16],[
17]. 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 also with the New York Heart Association (NYHA) functional class [
18].
Because binding sites are excessively expressed in 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-MI HF. Animal studies were conducted in rats 2 and 4 weeks after MI based on our previous studies with mice [
19],[
20], which demonstrated a peak in fibrosis-tracer uptake at those time points. Prior to animal studies, chemical and binding properties of IG3 were tested
in vitro using solid-phase assays.