Comparison of Somatostatin Receptor 2-Targeting PET Tracers in the Detection of Mouse Atherosclerotic Plaques

Petteri Rinne, Sanna Hellberg, Max Kiugel, Jenni Virta, Xiang-Guo Li, Meeri Käkelä, Kerttuli Helariutta, Pauliina Luoto, Heidi Liljenbäck, Harri Hakovirta, Maria Gardberg, Anu J Airaksinen, Juhani Knuuti, Antti Saraste, Anne Roivainen
Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging 2016, 18 (1): 99-108

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.

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