Journal of Nuclear Cardiology | 2019
68Ga-labeled exendin-4 to image cardiac repair after myocardial infarction: From lizard venom to laboratory and beyond
Abstract
Acute myocardial infarction (MI) and ischemic cardiomyopathy are major causes of death and disability worldwide. The inflammatory response after MI (Figure 1) plays a critical role in determining MI size. A persistent pro-inflammatory reaction can contribute significantly to adverse left ventricular remodeling, making inflammation an important target for imaging and therapy. Glucagon-like peptide-1 (GLP-1) and its G-proteincoupled receptor, the GLP-1 receptor (GLP-1R), have been shown to exhibit cardioprotective effects after myocardial ischemia and reperfusion injury in both animal models and clinical trials. GLP-1 is an intestinal peptide hormone stimulating insulin secretion after a meal. GLP-1Rs are present on pancreatic b-cells and expressed in other tissues such as the brain, kidneys, lungs, the immune system, stomach, and small and large intestines. GLP-1R has also been identified in the cardiovascular system. Cardiac imaging of GLP-1R may be an interesting target because its activation has been shown to induce differentiation of human macrophages into an anti-inflammatory or reparative M2 phenotype via STAT3 activation, increase the amount of M2 macrophages after MI, and attenuate myocardial inflammation and interstitial fibrosis post MI. Previously, GLP-1 agonists such as exendin-4 have been radiolabeled with positron emitters to image pancreatic tumors. Exendin-4 is a 39-amino acid peptide that was originally found in the venom of the Gila monster lizard and shares a 53% amino acid identity with GLP-1. Exendins are named as such because they were isolated from an exocrine gland and were shown to have endocrine actions. Compared to native GLP-1, exendin-4 is a long acting agonist at the GLP-1R but otherwise displays similar properties to GLP-1 in regulating gastric emptying, insulin secretion, inhibition of glucagon secretion, and appetite reduction.