Evaluation of [Ga]Ga-NODAGA-RGD for PET Imaging of Rat Autoimmune Myocarditis.

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