Cardiovascular Research Advance Access originally published online on February 6, 2008
Cardiovascular Research 2008 78(2):395-403; doi:10.1093/cvr/cvn033
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Assessment of
vβ3 integrin expression after myocardial infarction by positron emission tomography
1 Nuklearmedizinische Klinik und Poliklinik der Technischen Universität München, Klinikum rechts der Isar, Ismaninger Straße 22, 81675 Munich, Germany
2 Institut für Allgemeine Pathologie und Pathologische Anatomie der Technischen Universität München, Klinikum rechts der Isar, Munich, Germany
3 Center of Integrated Protein Science in Department Chemie, Lehrstuhl II für Organische Chemie, Technische Universität München, Munich, Germany
4 Abteilung für Gefässchirurgie der Technischen Universität München, Klinikum rechts der Isar, Munich, Germany
* Corresponding author. Tel: +49 89 4140 2968; fax: +49 89 4140 4950. E-mail address: higuchi{at}po2.nsknet.or.jp
Aims: The purpose of this study was to determine the feasibility of a new positron emission tomography (PET) imaging approach using an 18F-labelled
vβ3 integrin antagonist (18F-Galacto-RGD) to monitor the integrin expression after myocardial infarction.
Methods and results: Male Wister rats were subjected to 20 min transient left coronary artery occlusion followed by reperfusion. Autoradiographic analysis and in vivo PET imaging were used to determine myocardial 18F-Galacto-RGD uptake at different time points following reperfusion.
Results: PET imaging and autoradiography demonstrated no significant focal myocardial 18F-Galacto-RGD uptake in non-operated control rats and at day 1 after reperfusion. However, focal accumulation in the infarct area started at day 3 (uptake ratio = 1.91 ± 0.22 vs. remote myocardium), peaked between 1 (3.43 ± 0.57) and 3 weeks (3.43 ± 0.95), and decreased to 1.96 ± 0.40 at 6 months after reperfusion. Pretreatment with
vβ3 integrin antagonist c(-RGDfV-) significantly decreased tracer uptake, indicating the specificity of tracer uptake. The time course of focal tracer uptake paralleled vascular density as measured by CD31 immunohistochemical analysis.
Conclusion: Regional 18F-Galacto-RGD accumulation suggests up-regulation of
vβ3 integrin expression after myocardial infarction, which peaks between 1 and 3 weeks and remains detectable until 6 months after reperfusion. This new PET tracer is promising for the monitoring of myocardial repair processes.
KEYWORDS Angiogenesis; Infarction; Ischaemia; Reperfusion; Endothelial receptors
Time for primary review: 21 days
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