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Published in: Molecular Imaging and Biology 6/2014

01-12-2014 | Research Article

Dimeric [68Ga]DOTA-RGD Peptide Targeting αvβ3 Integrin Reveals Extracellular Matrix Alterations after Myocardial Infarction

Authors: Max Kiugel, Ingrid Dijkgraaf, Ville Kytö, Semi Helin, Heidi Liljenbäck, Tiina Saanijoki, Cheng-Bin Yim, Vesa Oikonen, Pekka Saukko, Juhani Knuuti, Anne Roivainen, Antti Saraste

Published in: Molecular Imaging and Biology | Issue 6/2014

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Abstract

Purpose

We evaluated a dimeric RGD-peptide, [68Ga]DOTA-E-[c(RGDfK)]2, for positron emission tomography (PET) imaging of myocardial integrin expression associated with extracellular matrix remodeling after myocardial infarction (MI) in rat.

Procedures

Male Sprague-Dawley rats were studied at 7 days and 4 weeks after MI induced by permanent ligation of the left coronary artery and compared with sham-operated controls.

Results

In vivo imaging revealed higher tracer uptake in the infarcted area than in the remote non-infarcted myocardium of the same rats both at 7 days (MI/remote ratio, 2.25 ± 0.24) and 4 weeks (MI/remote ratio, 2.13 ± 0.37) post-MI. Compared with sham-operated rats, tracer uptake was higher also in the remote, non-infarcted myocardium of MI rats both at 7 days and 4 weeks where it coincided with an increased interstitial fibrosis. Standardized uptake values correlated well with the results of tracer kinetic modeling. Autoradiography confirmed the imaging results showing 5.1 times higher tracer uptake in the infarcted than remote area. Tracer uptake correlated with the amount of β3 integrin subunits in the infarcted area.

Conclusions

Our results show that integrin-targeting [68Ga]DOTA-E-[c(RGDfK)]2 is a potential tracer for monitoring of myocardial extracellular matrix remodeling after MI using PET.
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Metadata
Title
Dimeric [68Ga]DOTA-RGD Peptide Targeting αvβ3 Integrin Reveals Extracellular Matrix Alterations after Myocardial Infarction
Authors
Max Kiugel
Ingrid Dijkgraaf
Ville Kytö
Semi Helin
Heidi Liljenbäck
Tiina Saanijoki
Cheng-Bin Yim
Vesa Oikonen
Pekka Saukko
Juhani Knuuti
Anne Roivainen
Antti Saraste
Publication date
01-12-2014
Publisher
Springer US
Published in
Molecular Imaging and Biology / Issue 6/2014
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI
https://doi.org/10.1007/s11307-014-0752-1

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