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

Abstract

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 αvβ3 integrin that is upregulated during angiogenesis and inflammation. We studied whether αvβ3 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 (SUVmean 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 αvβ3 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 αvβ3 integrin-targeting [68Ga]Ga-NODAGA-RGD is a potential PET tracer for the specific detection of active inflammatory lesions in autoimmune myocarditis.

Super Early Scan of PSMA PET/CT in Evaluating Primary and Metastatic Lesions of Prostate Cancer

“…In addition, regarding the imaging of lesions with targets expressed on blood vessels or cell membranes, such as RGD-targeted and VEGF-targeted imaging, there is also potential to distinguish the lesions from the metabolic organs at the super early stage, benefiting from the early implementation of targeting [ 25 , 26 ].…”

STING-Targeted PET Imaging for Specific Detection and Therapeutic Monitoring of Myocarditis

“…2 translocator protein (TSPO) targeted probes, [ 18 F]-Fluoromethyl-PBR28 and [ 18 F]CB251, 5 and the pathologic uptake of somatostatin receptor-based probe [ 68 Ga]Ga-DOTATOC in the paravertebral and intercostal muscles can interfere with imaging observations of inflammatory myocardial lesions. 6 The clinical utilization of [ F]FLO, 8 the mannose-targeted probe [ 68 Ga]Ga-NOTA-MSA, 9 and the αvβ3 integrin-targeted probe [ 68 Ga]Ga-NODAGA-RGD, 10 are expressed not only in macrophages but also in a wide range of epithelial cells 12 or endothelial cells, 10,13 so the specificity of imaging is greatly limited.…”

“…CMRI findings mainly reflect indirect indicators of myocardial inflammation, including edema, hyperemia, ischemia, and fibrosis, a lack of robust histologic validation of inflammation, and the ability to diagnose early active inflammation. PET imaging molecular probes to assess myocarditis also have certain limitations. − [ 18 F]­FDG-PET imaging is still not a preferred diagnostic approach for myocarditis in clinical trials and consensuses . Specificity of [ 18 F]­FDG is hampered by the physiological glucose uptake of the cardiocytes .…”

“…The clinical utilization of [ 11 C]­C-methionine may be limited by the short physical half-life of 11 C (20.4 min), especially in PET/computed tomography (CT) centers that lack cyclotron and drug synthesis device platforms. Tracers targeting macrophage receptors, such as the folate receptor β-targeted probe [ 18 F]­FLO, the mannose-targeted probe [ 68 Ga]­Ga-NOTA-MSA, and the αvβ3 integrin-targeted probe [ 68 Ga]­Ga-NODAGA-RGD, are expressed not only in macrophages but also in a wide range of epithelial cells or endothelial cells, , so the specificity of imaging is greatly limited.…”