Purpose: Rupture-prone atherosclerotic plaques are characterized by accumulation of macrophages, which have shown to express somatostatin type 2 receptors. We aimed to investigate whether somatostatin receptor-targeting positron emission tomography (PET) tracers, [(68)Ga]DOTANOC, [(18)F]FDR-NOC, and [(68)Ga]DOTATATE, can detect inflamed atherosclerotic plaques.
Procedures: Atherosclerotic IGF-II/LDLR(-/-)ApoB(100/100) mice were studied in vivo and ex vivo for tracer uptake into atherosclerotic plaques. Furthermore, [(68)Ga]DOTANOC and [(68)Ga]DOTATATE were compared in a head-to-head setting for in vivo PET/X-ray computed tomography (CT) imaging characteristics.
Results: Ex vivo uptake of [(68)Ga]DOTANOC and [(68)Ga]DOTATATE in the aorta was higher in atherosclerotic mice compared to control C57Bl/6N mice, while the aortic uptake of [(18)F]FDR-NOC showed no genotype difference. Unlike [(18)F]FDR-NOC, [(68)Ga]DOTANOC and [(68)Ga]DOTATATE showed preferential binding to atherosclerotic plaques with plaque-to-wall ratio of 1.7 ± 0.3 and 2.1 ± 0.5, respectively. However, the aortic uptake and aorta-to-blood ratio of [(68)Ga]DOTANOC were higher compared to [(68)Ga]DOTATATE in in vivo PET/CT imaging.
Conclusion: Our results demonstrate superior applicability for [(68)Ga]DOTANOC and [(68)Ga]DOTATATE in the detection of atherosclerotic plaques compared to [(18)F]FDR-NOC.
Keywords: Atherosclerosis; Autoradiography; Biodistribution; Positron emission tomography; Somatostatin receptor.