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European Journal of Nuclear Medicine and Molecular Imaging

Erschienen in:

01.08.2013 | Original Article

MicroPET/CT imaging of α_vβ₃ integrin via a novel ⁶⁸Ga-NOTA-RGD peptidomimetic conjugate in rat myocardial infarction

verfasst von: Luca Menichetti, Claudia Kusmic, Daniele Panetta, Daniela Arosio, Debora Petroni, Marco Matteucci, Piero A. Salvadori, Cesare Casagrande, Antonio L’Abbate, Leonardo Manzoni

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 8/2013

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Abstract

Purpose

The α_vβ₃ integrin is expressed in angiogenic vessels and is a potential target for molecular imaging of evolving pathological processes. Its expression is upregulated in cancer lesions and metastases as well as in acute myocardial infarction (MI) as part of the infarct healing process. The purpose of our study was to determine the feasibility of a new imaging approach with a novel ⁶⁸Ga-2,2′,2″-(1,4,7-triazonane-1,4,7-triyl)triacetic acid (NOTA)-arginine-glycine-aspartic acid (RGD) construct to assess integrin expression in the evolving MI.

Methods

A straightforward labelling chemistry to attach the radionuclide ⁶⁸Ga to a NOTA-based chelating agent conjugated with a cyclic RGD peptidomimetic is described. Affinity for α_vβ₃ integrin was assessed by in vitro receptor binding assay. The proof-of-concept in vivo studies combined the ⁶⁸Ga-NOTA-RGD with the flow tracer ¹³N-NH₃ imaging in order to obtain positron emission tomography (PET)/CT imaging of both integrin expression and perfusion defect at 4 weeks after infarction. Hearts were then processed for immunostaining of integrin β₃.

Results

NOTA-RGD conjugate displayed a binding affinity for α_vβ₃ integrin of 27.9 ± 6.8 nM. ⁶⁸Ga-NOTA-RGD showed stability without detectable degradation or formation of by-products in urine up to 2 h following injection in the rat. MI hearts exhibited ⁶⁸Ga-NOTA-RGD uptake in correspondence to infarcted and border zone regions. The tracer signal drew a parallel with vascular remodelling due to ischaemia-induced angiogenesis as assessed by immunohistochemistry.

Conclusion

As compared to similar imaging approaches using the ¹⁸F-galacto-derivative, we documented for the first time with microPET/CT imaging the ⁶⁸Ga-NOTA-RGD derivative that appears eligible for PET imaging in animal models of vascular remodelling during evolving MI. The simple chemistry employed to synthesize the ⁶⁸Ga-based radiotracer may greatly facilitate its translation to a clinical setting.

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Titel: MicroPET/CT imaging of αvβ3 integrin via a novel 68Ga-NOTA-RGD peptidomimetic conjugate in rat myocardial infarction
verfasst von: Luca Menichetti
Claudia Kusmic
Daniele Panetta
Daniela Arosio
Debora Petroni
Marco Matteucci
Piero A. Salvadori
Cesare Casagrande
Antonio L’Abbate
Leonardo Manzoni
Publikationsdatum: 01.08.2013
Verlag: Springer Berlin Heidelberg
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 8/2013
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-013-2432-9

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

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