Author + information
Background: Experimental research signifies myocardial cannabinoid type 1 receptor (CB1-R) activation via endocannabinoids to induced cardiac dysfunction. We aimed to evaluate the feasibility of targeted imaging myocardial CB1-R and its potential up-regulation from normal weight to obese mice with translation to humans using the radiotracer [11C]-OMAR and PET/CT.
Methods: Applying the CB1-R ligand [11C]-OMAR, dynamic micro PET/CT was carried out in five normal weight and seven obese mice. Ex vivo validation was performed with droplet digital polymerase chain reaction (PCR). Subsequently, myocardial CB1-R expression was probed non-invasively with intravenous injection of CB1-R ligand [11C]-OMAR and PET/CT in five morbidly obese individuals (MOB; BMI ≥40kg/m2) and normal weight controls (CON; BMI<25kg/m2), respectively.
Results: Quantifications of the myocardial OMAR retention in mice proved to be significantly higher in obese than in normal weight mice [8.13 (2.87, 11.74) %/min vs. 0.10 (0.03, 0.11) %/min, p=0.015]. Absolute quantification of CB1-R gene expression with droplet digital PCR confirmed CB1-R up-regulation in obese [73.7 (68.1, 75.9)] copies/μL versus normal weight mice [54.5 (50.5, 57.8) copies/μL, p≤0.05]. Translation to humans also signified a significantly higher OMAR retention in MOB than in CON [5.88 (2.06, 7.16) %/min vs. 0.51 (0.33, 1.19) %/min, p=0.015].
Conclusions: Noninvasive imaging of cardiac CB1-receptor expression with [11C]-OMAR and PET/CT signifies an up-regulation of cardiac CB1-receptor expression. As an activation of myocardial CB1-receptors via endocannabinoids may lead to cardiac dysfunction, the observed up-regulation of myocardial CB1 receptors may provide a mechanistic link between obesity and the initiation and/or progression of obesity related cardiomyopathy needing further investigations.
Poster Hall, Hall C
Saturday, March 18, 2017, 9:45 a.m.-10:30 a.m.
Session Title: Nuclear Cardiology: Beyond Perfusion
Abstract Category: 30. Non Invasive Imaging: Nuclear
Presentation Number: 1196-197
- 2017 American College of Cardiology Foundation