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MicroPET/CT imaging of αvβ3 integrin via a novel 68Ga-NOTA-RGD peptidomimetic conjugate in rat myocardial infarction

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

The αvβ3 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 αvβ3 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 αvβ3 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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Acknowledgments

This work was supported by the Consiglio Nazionale delle Ricerche, Italy (grant CNR-DG.RSTL.035.007-035), Scuola Superiore Sant’Anna, Italy (grant PNAZ.M6010AL).

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. CNR-Institute of Clinical Physiology (IFC), Via Moruzzi 1, 56124, Pisa, Italy

    Luca Menichetti, Claudia Kusmic, Daniele Panetta, Debora Petroni, Piero A. Salvadori & Antonio L’Abbate

  2. CNR-Institute of Molecular Science and Technologies (ISTM), Via C. Golgi 19, 20133, Milan, Italy

    Daniela Arosio & Leonardo Manzoni

  3. Scuola Superiore Sant’Anna, Piazza Martiri della Libertà 33, 56127, Pisa, Italy

    Marco Matteucci & Antonio L’Abbate

  4. Department of Chemistry, University of Milan, Via C. Golgi 19, 20133, Milan, Italy

    Cesare Casagrande

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  1. Luca Menichetti
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Correspondence to Luca Menichetti or Leonardo Manzoni.

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Menichetti, L., Kusmic, C., Panetta, D. et al. MicroPET/CT imaging of αvβ3 integrin via a novel 68Ga-NOTA-RGD peptidomimetic conjugate in rat myocardial infarction. Eur J Nucl Med Mol Imaging 40, 1265–1274 (2013). https://doi.org/10.1007/s00259-013-2432-9

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  • DOI: https://doi.org/10.1007/s00259-013-2432-9

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