Abstract | PURPOSE: METHODS: A straightforward labelling chemistry to attach the radionuclide (68)Ga 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 (68)Ga-NOTA-RGD with the flow tracer (13)N-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. (68)Ga-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 (68)Ga-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 (18)F-galacto-derivative, we documented for the first time with microPET/CT imaging the (68)Ga-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 (68)Ga-based radiotracer may greatly facilitate its translation to a clinical setting.
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Authors | Luca Menichetti, Claudia Kusmic, Daniele Panetta, Daniela Arosio, Debora Petroni, Marco Matteucci, Piero A Salvadori, Cesare Casagrande, Antonio L'Abbate, Leonardo Manzoni |
Journal | European journal of nuclear medicine and molecular imaging
(Eur J Nucl Med Mol Imaging)
Vol. 40
Issue 8
Pg. 1265-74
(Aug 2013)
ISSN: 1619-7089 [Electronic] Germany |
PMID | 23674206
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 68Ga-1,4,7-triazacyclononane-1,4-7-triacetic acid-isothiocyanatobenzyl-c(Arg-Gly-Asp-Tyr-Lys)
- Coordination Complexes
- Integrin alphaVbeta3
- Oligopeptides
- Peptides, Cyclic
- Radiopharmaceuticals
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Topics |
- Animals
- Coordination Complexes
(chemical synthesis, chemistry, pharmacokinetics)
- Integrin alphaVbeta3
(metabolism)
- Male
- Multimodal Imaging
- Myocardial Infarction
(diagnostic imaging)
- Oligopeptides
(chemistry)
- Peptides, Cyclic
(chemical synthesis, chemistry, pharmacokinetics)
- Positron-Emission Tomography
- Protein Binding
- Radiopharmaceuticals
(chemical synthesis, chemistry, pharmacokinetics)
- Rats
- Rats, Wistar
- Tomography, X-Ray Computed
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