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PET imaging of angiogenesis after myocardial infarction/reperfusion using a one-step labeled integrin-targeted tracer 18F-AlF-NOTA-PRGD2

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

The αvβ3 integrin represents a potential target for noninvasive imaging of angiogenesis. The purpose of this study was to evaluate a novel one-step labeled integrin αvβ3-targeting positron emission tomography (PET) probe, 18F-AlF-NOTA-PRGD2, for angiogenesis imaging in a myocardial infarction/reperfusion (MI/R) animal model.

Methods

Male Sprague-Dawley rats underwent 45-min transient left coronary artery occlusion followed by reperfusion. The myocardial infarction was confirmed by ECG, 18F-fluorodeoxyglucose (FDG) imaging, and cardiac ultrasound. In vivo PET imaging was used to determine myocardial uptake of 18F-AlF-NOTA-PRGD2 at different time points following reperfusion. The control peptide RAD was labeled with a similar procedure and used to confirm the specificity. Ex vivo autoradiographic analysis and CD31/CD61 double immunofluorescence staining were performed to validate the PET results.

Results

Myocardial origin of the 18F-AlF-NOTA-PRGD2 accumulation was confirmed by 18F-FDG and autoradiography. PET imaging demonstrated increased focal accumulation of 18F-AlF-NOTA-PRGD2 in the infarcted area which started at day 3 (0.28 ± 0.03%ID/g, p < 0.05) and peaked between 1 and 3 weeks (0.59 ± 0.16 and 0.55 ± 0.13%ID/g, respectively). The focal accumulation decreased but still kept at a higher level than the sham group after 4 months of reperfusion (0.31 ± 0.01%ID/g, p < 0.05). Pretreatment with unlabeled arginine-glycine-aspartic acid (RGD) peptide significantly decreased tracer uptake, indicating integrin specificity of this tracer. At 1 week after MI/R, uptake of the control tracer 18F-AlF-NOTA-RAD that does not bind to integrin, in the infarcted area, was only 0.21 ± 0.01%ID/g. Autoradiographic imaging showed the same trend of uptake in the myocardial infarction area. The time course of focal tracer uptake was consistent with the pattern of vascular density and integrin β3 expression as measured by CD31 and CD61 immunostaining analysis.

Conclusion

PET imaging using one-step labeled 18F-AlF-NOTA-PRGD2 allows noninvasive visualization of ischemia/reperfusion-induced myocardial angiogenesis longitudinally. The favorable in vivo kinetics and easy production method of this integrin-targeted PET tracer facilitates its future clinical translation for lesion evaluation and therapy response monitoring in patients with occlusive cardiovascular diseases.

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Acknowledgment

This project was supported by the Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH) and the International Cooperative Program of the National Science Foundation of China (NSFC) (81028009). H.G. is partly supported by the National Science Foundation of China (NSFC) (81100234).

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Authors and Affiliations

  1. Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xi’an, China, 710032

    Haokao Gao & Feng Cao

  2. Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), 31 Center Drive, Suite 1C14, Bethesda, MD, 20892-2281, USA

    Haokao Gao, Lixin Lang, Ning Guo, Qimeng Quan, Shuo Hu, Dale O. Kiesewetter, Gang Niu & Xiaoyuan Chen

  3. 9 Memorial Drive, 9/1W111, Bethesda, MD, 20892, USA

    Gang Niu

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  1. Haokao Gao
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Correspondence to Gang Niu or Xiaoyuan Chen.

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Gao, H., Lang, L., Guo, N. et al. PET imaging of angiogenesis after myocardial infarction/reperfusion using a one-step labeled integrin-targeted tracer 18F-AlF-NOTA-PRGD2. Eur J Nucl Med Mol Imaging 39, 683–692 (2012). https://doi.org/10.1007/s00259-011-2052-1

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  • DOI: https://doi.org/10.1007/s00259-011-2052-1

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