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

The ⁶⁸Gallium-labeled 1,4,7-triazacyclononane-1-glutaric acid-4,7-diacetic acid conjugated radiolabelled arginine-glycine-aspartic acid peptide ([⁶⁸Ga]Ga-NODAGA-RGD) is a positron emission tomography (PET) tracer binding to cell surface receptor α_vβ₃ integrin that is upregulated during angiogenesis and inflammation. We studied whether α_vβ₃ targeting PET imaging can detect myocardial inflammation in a rat model of autoimmune myocarditis. To induce myocarditis, rats (n = 8) were immunized with porcine cardiac myosin in complete Freund's adjuvant on days 0 and 7. Control rats (n = 8) received Freund's adjuvant alone. On day 21, in vivo PET/CT imaging with [⁶⁸Ga]Ga-NODAGA-RGD followed by ex vivo autoradiography and immunohistochemistry were carried out. Inflammatory lesions were detected histologically in the myocardium of 7 out of 8 immunized rats. In vivo PET images showed higher [⁶⁸Ga]Ga-NODAGA-RGD accumulation in the myocardium of rats with inflammation than the non-inflamed myocardium of control rats (SUV_mean 0.4 ± 0.1 vs. 0.1 ± 0.02; P = 0.00006). Ex vivo autoradiography and histology confirmed that [⁶⁸Ga]Ga-NODAGA-RGD uptake co-localized with inflammatory lesions containing α_vβ₃ integrin-positive capillary-like structures. A non-specific [⁶⁸Ga]Ga-DOTA-(RGE)₂ tracer showed 76% lower uptake than [⁶⁸Ga]Ga-NODAGA-RGD in the inflamed myocardium. Our results indicate that α_vβ₃ integrin-targeting [⁶⁸Ga]Ga-NODAGA-RGD is a potential PET tracer for the specific detection of active inflammatory lesions in autoimmune myocarditis.