title: Labeling galectin-3 for the assessment of myocardial infarction in rats.
abstract: BACKGROUND
  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. The aim of this study is to test the ability of (123)I-galectin-3 (IG3) to assess cardiac remodeling in a model of myocardial infarction (MI) using imaging techniques.
  
  
  METHODS
  Recombinant galectin-3 was labeled with iodine-123 and in vitro binding assays were conducted to test (123)I-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.
  
  
  RESULTS
  In 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 (r s = 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 μm(2)) compared to control (4.7 ± 2.0 μm(2), p < 0.001) and 2 W-MI (10.6 ± 5.1 μm(2), p < 0.05).
  
  
  CONCLUSIONS
  This 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.
authors.affiliation: Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1030, New York, NY, 10029, USA, tvarias@cnic.es.
authors.forename: Teresa
authors.initials: T
authors.lastname: Arias
authors.forename: Artiom
authors.initials: A
authors.lastname: Petrov
authors.forename: Jiqiu
authors.initials: J
authors.lastname: Chen
authors.forename: Hans
authors.initials: H
authors.lastname: de Haas
authors.forename: Carlos
authors.initials: C
authors.lastname: Pérez-Medina
authors.forename: Gustav J
authors.initials: GJ
authors.lastname: Strijkers
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Hajjar
authors.forename: Zahi A
authors.initials: ZA
authors.lastname: Fayad
authors.forename: Valentín
authors.initials: V
authors.lastname: Fuster
authors.forename: Jagat
authors.initials: J
authors.lastname: Narula