Objectives: Glucagon-like peptide-1 receptor (GLP-1R) is expressed in the heart and may have cardioprotective effects. We evaluated ⁶⁸Ga-NODAGA-Exendin-4 for monitoring the level of GLP-1R expression in the heart after experimental myocardial infarction (MI).

Methods: Rats were studied at 1 wk (n=7) and at 12 wk (n=6) after induction of MI by permanent ligation of the left coronary artery or at the same time-points after sham-operation (n=9 and n=5, respectively). After 54±3 MBq injection of ⁶⁸Ga-NODAGA-Exendin-4, 60 min dynamic PET and contrast-enhanced CT were performed. After imaging, left ventricle (LV) was cut into serial short axis cryosections for autoradiography, histology and immunohistochemistry.

Results: Average MI size measured as percentage of LV circumference was 42±7 % at 1 wk and 37±14 % at 12 wk. In vivo imaging showed ⁶⁸Ga-NODAGA-Exendin-4 uptake at the infarcted anterior wall of the LV. Compared with the myocardium of sham-operated rats, autoradiography showed increased (p<0.001) tracer uptake in the infarct scar and in the surrounding border zone myocardium at 1 wk post-MI (0.8±0.4 vs. 6.6±2.3 and 2.2±0.5 PSL/mm², respectively) as well as at 12 wk post-MI (1.0±0.4 vs. 4.1±1.1 and 2.5±0.7 PSL/mm², respectively). Tracer uptake was slightly increased (p<0.05 vs. sham) also in the remote, non-infarcted myocardium at 1 and 12 wk post-MI (1.4±0.5 and 1.5±0.4 PSL/mm², respectively). GLP-1R expression at MI was confirmed by immunohistochemistry. ⁶⁸Ga-NODAGA-Exendin-4 uptake was significantly blocked with an excess amount of unlabeled peptide.

Conclusions: ⁶⁸Ga-NODAGA-Exendin-4 detects increased myocardial GLP-1R expression extending to 3 months after MI. Imaging of GLP-1R may help to study the functions and therapeutic potential of incretins in the heart.