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European Journal of Nuclear Medicine and Molecular Imaging

Published in:

01-04-2012 | Original Article

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

Authors: Haokao Gao, Lixin Lang, Ning Guo, Feng Cao, Qimeng Quan, Shuo Hu, Dale O. Kiesewetter, Gang Niu, Xiaoyuan Chen

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 4/2012

Abstract

Purpose

The α_vβ₃ integrin represents a potential target for noninvasive imaging of angiogenesis. The purpose of this study was to evaluate a novel one-step labeled integrin α_vβ₃-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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Title: PET imaging of angiogenesis after myocardial infarction/reperfusion using a one-step labeled integrin-targeted tracer 18F-AlF-NOTA-PRGD2
Authors: Haokao Gao
Lixin Lang
Ning Guo
Feng Cao
Qimeng Quan
Shuo Hu
Dale O. Kiesewetter
Gang Niu
Xiaoyuan Chen
Publication date: 01-04-2012
Publisher: Springer-Verlag
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 4/2012
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-011-2052-1

At a glance: The STEP trials

Springer Medicine

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

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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The 47th Seminar of the European School of Nuclear Medicine (ESNM) May 13–15, 2011, and the 7th International Congress of the Croatian Society of Nuclear Medicine May 15–18, 2011, Opatija, Croatia