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EJNMMI Research
Published in: EJNMMI Research 1/2013

Open Access 01-12-2013 | Original research

Comparison of cyclic RGD peptides for αvβ3 integrin detection in a rat model of myocardial infarction

Authors: Iina Laitinen, Johannes Notni, Karolin Pohle, Martina Rudelius, Eliane Farrell, Stephan G Nekolla, Gjermund Henriksen, Stefanie Neubauer, Horst Kessler, Hans-Jürgen Wester, Markus Schwaiger

Published in: EJNMMI Research | Issue 1/2013

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Abstract

Background

Expression of αvβ3 integrin is increased after myocardial infarction as part of the repair process. Increased expression of αvβ3 has been shown by molecular imaging with 18F-galacto-RGD in a rat model. The 68Ga-labelled RGD compounds 68Ga-NODAGA-RGD and 68Ga-TRAP(RGD)3 have high specificity and affinity, and may therefore serve as alternatives of 18F-galacto-RGD for integrin imaging.

Methods

Left coronary artery ligation was performed in rats. After 1 week, rats were imaged with [13N]NH3, followed by 18F-galacto-RGD, 68Ga-NODAGA-RGD or 68Ga-TRAP(RGD)3 using a dedicated animal PET/CT device. Rats were killed, and the activity in tissues was measured by gamma counting. The heart was sectioned for autoradiography and histology. Immunohistochemistry was performed on consecutive sections using CD31 for the endothelial cells and CD61 for β3 expression (as part of the αvβ3 receptor).

Results

In vivo imaging showed focal RGD uptake in the hypoperfused area of infarcted myocardium as defined with [13N]NH3 scan. In autoradiography images, augmented uptake of all RGD tracers was observed within the infarct area as verified by the HE staining. The tracer uptake ratios (infarct vs. remote) were 4.7 ± 0.8 for 18F-galacto-RGD, 5.2 ± 0.8 for 68Ga-NODAGA-RGD, and 4.1 ± 0.7 for 68Ga-TRAP(RGD)3. The 68Ga-NODAGA-RGD ratio was higher compared to 68Ga-TRAP(RGD)3 (p = 0.04), but neither of the 68Ga tracers differed from 18F-galacto-RGD (p > 0.05). The area of augmented 68Ga-RGD uptake was associated with β3 integrin expression (CD61).

Conclusion

68Ga-NODAGA-RGD and 68Ga-TRAP(RGD)3 uptake was equally increased in the infarct area at 1 week post infarction as 18F-galacto-RGD. These results show the potential of 68Ga-labelled RGD peptides to monitor integrin expression as a part of myocardial repair and angiogenesis after ischaemic injury in vivo.
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Metadata
Title
Comparison of cyclic RGD peptides for αvβ3 integrin detection in a rat model of myocardial infarction
Authors
Iina Laitinen
Johannes Notni
Karolin Pohle
Martina Rudelius
Eliane Farrell
Stephan G Nekolla
Gjermund Henriksen
Stefanie Neubauer
Horst Kessler
Hans-Jürgen Wester
Markus Schwaiger
Publication date
01-12-2013
Publisher
Springer Berlin Heidelberg
Published in
EJNMMI Research / Issue 1/2013
Electronic ISSN: 2191-219X
DOI
https://doi.org/10.1186/2191-219X-3-38

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