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

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Abstract

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, [68Ga]DOTANOC, [18F]FDR-NOC, and [68Ga]DOTATATE, can detect inflamed atherosclerotic plaques.

Procedures

Atherosclerotic IGF-II/LDLR−/−ApoB100/100 mice were studied in vivo and ex vivo for tracer uptake into atherosclerotic plaques. Furthermore, [68Ga]DOTANOC and [68Ga]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 [68Ga]DOTANOC and [68Ga]DOTATATE in the aorta was higher in atherosclerotic mice compared to control C57Bl/6N mice, while the aortic uptake of [18F]FDR-NOC showed no genotype difference. Unlike [18F]FDR-NOC, [68Ga]DOTANOC and [68Ga]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 [68Ga]DOTANOC were higher compared to [68Ga]DOTATATE in in vivo PET/CT imaging.

Conclusion

Our results demonstrate superior applicability for [68Ga]DOTANOC and [68Ga]DOTATATE in the detection of atherosclerotic plaques compared to [18F]FDR-NOC.

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Acknowledgments

The authors wish to thank Riikka Siitonen and Aake Honkaniemi for assistance in mouse experiments and Erica Nyman and Sinikka Collanus for technical assistance in tissue sectioning and immunohistochemistry. This study was conducted within the Finnish Center of Excellence in Cardiovascular and Metabolic Diseases supported by the Academy of Finland, the University of Turku, the Turku University Hospital, and the Åbo Akademi University.

Conflict of Interest

The authors declare that they have no conflict of interest.

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    Authors and Affiliations

    1. Turku PET Centre, Turku University Hospital and University of Turku, Kiinamyllynkatu 4-8, FI-20520, Turku, Finland

      Petteri Rinne, Sanna Hellberg, Max Kiugel, Jenni Virta, Xiang-Guo Li, Meeri Käkelä, Pauliina Luoto, Heidi Liljenbäck, Juhani Knuuti, Antti Saraste & Anne Roivainen

    2. Laboratory of Radiochemistry, Department of Chemistry, University of Helsinki, Helsinki, Finland

      Kerttuli Helariutta & Anu J. Airaksinen

    3. Turku Center for Disease Modeling, University of Turku, Turku, Finland

      Heidi Liljenbäck & Anne Roivainen

    4. Department of Surgery, University of Turku, Turku, Finland

      Harri Hakovirta

    5. Department of Pathology, Turku University Hospital and University of Turku, Turku, Finland

      Maria Gardberg

    6. Heart Center, Turku University Hospital and University of Turku, Turku, Finland

      Antti Saraste

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    1. Petteri Rinne
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    Correspondence to Anne Roivainen.

    Additional information

    Petteri Rinne and Sanna Hellberg contributed equally to this work.

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    Rinne, P., Hellberg, S., Kiugel, M. et al. Comparison of Somatostatin Receptor 2-Targeting PET Tracers in the Detection of Mouse Atherosclerotic Plaques. Mol Imaging Biol 18, 99–108 (2016). https://doi.org/10.1007/s11307-015-0873-1

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