AUTHOR=Jahandideh Arghavan , Ståhle Mia , Virta Jenni , Li Xiang-Guo , Liljenbäck Heidi , Moisio Olli , Knuuti Juhani , Roivainen Anne , Saraste Antti 

TITLE=Evaluation of [68Ga]Ga-NODAGA-RGD for PET Imaging of Rat Autoimmune Myocarditis

JOURNAL=Frontiers in Medicine

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.783596

DOI=10.3389/fmed.2021.783596

ISSN=2296-858X

ABSTRACT=<p>The <sup>68</sup>Gallium-labeled 1,4,7-triazacyclononane-1-glutaric acid-4,7-diacetic acid conjugated radiolabelled arginine-glycine-aspartic acid peptide ([<sup>68</sup>Ga]Ga-NODAGA-RGD) is a positron emission tomography (PET) tracer binding to cell surface receptor α<sub>v</sub>β<sub>3</sub> integrin that is upregulated during angiogenesis and inflammation. We studied whether α<sub>v</sub>β<sub>3</sub> targeting PET imaging can detect myocardial inflammation in a rat model of autoimmune myocarditis. To induce myocarditis, rats (<italic>n</italic> = 8) were immunized with porcine cardiac myosin in complete Freund's adjuvant on days 0 and 7. Control rats (<italic>n</italic> = 8) received Freund's adjuvant alone. On day 21, <italic>in vivo</italic> PET/CT imaging with [<sup>68</sup>Ga]Ga-NODAGA-RGD followed by <italic>ex vivo</italic> autoradiography and immunohistochemistry were carried out. Inflammatory lesions were detected histologically in the myocardium of 7 out of 8 immunized rats. <italic>In vivo</italic> PET images showed higher [<sup>68</sup>Ga]Ga-NODAGA-RGD accumulation in the myocardium of rats with inflammation than the non-inflamed myocardium of control rats (SUV<sub>mean</sub> 0.4 ± 0.1 vs. 0.1 ± 0.02; <italic>P</italic> = 0.00006). <italic>Ex vivo</italic> autoradiography and histology confirmed that [<sup>68</sup>Ga]Ga-NODAGA-RGD uptake co-localized with inflammatory lesions containing α<sub>v</sub>β<sub>3</sub> integrin-positive capillary-like structures. A non-specific [<sup>68</sup>Ga]Ga-DOTA-(RGE)<sub>2</sub> tracer showed 76% lower uptake than [<sup>68</sup>Ga]Ga-NODAGA-RGD in the inflamed myocardium. Our results indicate that α<sub>v</sub>β<sub>3</sub> integrin-targeting [<sup>68</sup>Ga]Ga-NODAGA-RGD is a potential PET tracer for the specific detection of active inflammatory lesions in autoimmune myocarditis.</p>