MicroPET/CT imaging of alphavbeta3 integrin via a novel 68Ga-NOTA-RGD peptidomimetic conjugate in rat myocardial infarction (Articolo in rivista)

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  • MicroPET/CT imaging of alphavbeta3 integrin via a novel 68Ga-NOTA-RGD peptidomimetic conjugate in rat myocardial infarction (Articolo in rivista) (literal)
Anno
  • 2013-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1007/s00259-013-2432-9 (literal)
Alternative label
  • Luca Menichetti, Claudia Kusmic, Daniele Panetta, Daniela Arosio, Debora Petroni, Marco Matteucci, Piero A. Salvadori, Cesare Casagrande, Antonio L'Abbate, Leonardo Manzoni (2013)
    MicroPET/CT imaging of alphavbeta3 integrin via a novel 68Ga-NOTA-RGD peptidomimetic conjugate in rat myocardial infarction
    in European journal of nuclear medicine and molecular imaging (Print)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Luca Menichetti, Claudia Kusmic, Daniele Panetta, Daniela Arosio, Debora Petroni, Marco Matteucci, Piero A. Salvadori, Cesare Casagrande, Antonio L'Abbate, Leonardo Manzoni (literal)
Pagina inizio
  • 1265 (literal)
Pagina fine
  • 1274 (literal)
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  • 40 (literal)
Rivista
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  • 10 (literal)
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Luca Menichetti, Claudia Kusmic, Daniele Panetta, Debora Petroni, Piero A. Salvadori, CNR-Institute of Clinical Physiology (IFC), Via Moruzzi 1, Pisa, 56124, Italy. Daniela Arosio, Leonardo Manzoni, CNR-Institute of Molecular Science and Technologies (ISTM), Via C. Golgi 19, Milan, 20133, Italy. Marco Matteucci, Scuola Superiore Sant'Anna, Piazza Martiri della Libertà 33, Pisa, 56127, Italy. Cesare Casagrande, Department of Chemistry, University of Milan, Via C. Golgi 19, Milan, 20133, Italy. Antonio L'Abbate, CNR-Institute of Clinical Physiology (IFC), Via Moruzzi 1, Pisa, 56124, Italy and Scuola Superiore Sant'Anna, Piazza Martiri della Libertà 33, Pisa, 56127, Italy. (literal)
Titolo
  • MicroPET/CT imaging of alphavbeta3 integrin via a novel 68Ga-NOTA-RGD peptidomimetic conjugate in rat myocardial infarction (literal)
Abstract
  • Purpose: The alphavbeta3 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 alphavbeta3 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 beta3. Results: NOTA-RGD conjugate displayed a binding affinity for alphavbeta3 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. (literal)
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