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

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 (68)Ga-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 (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.