Application of (68)Ga-PRGD2 PET/CT for αvβ3-integrin imaging of myocardial infarction and stroke

Theranostics. 2014 May 25;4(8):778-86. doi: 10.7150/thno.8809. eCollection 2014.

Abstract

Purpose: Ischemic vascular diseases, including myocardial infarction (MI) and stroke, have been found to be associated with elevated expression of αvβ3-integrin, which provides a promising target for semi-quantitative monitoring of the disease. For the first time, we employed (68)Ga-S-2-(isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid-PEG3-E[c(RGDyK)]2 ((68)Ga-PRGD2) to evaluate the αvβ3-integrin-related repair in post-MI and post-stroke patients via positron emission tomography/computed tomography (PET/CT).

Methods: With Institutional Review Board approval, 23 MI patients (3 days-2 years post-MI) and 16 stroke patients (3 days-13 years post-stroke) were recruited. After giving informed consent, each patient underwent a cardiac or brain PET/CT scan 30 min after the intravenous injection of (68)Ga-PRGD2 in a dose of approximately 1.85 MBq (0.05 mCi) per kilogram body weight. Two stroke patients underwent repeat scans three months after the event.

Results: Patchy (68)Ga-PRGD2 uptake occurred in or around the ischemic regions in 20/23 MI patients and punctate multifocal uptake occurred in 8/16 stroke patients. The peak standardized uptake values (pSUVs) in MI were 1.94 ± 0.48 (mean ± SD; range, 0.62-2.69), significantly higher than those in stroke (mean ± SD, 0.46 ± 0.29; range, 0.15-0.93; P < 0.001). Higher (68)Ga-PRGD2 uptake was observed in the patients 1-3 weeks after the initial onset of the MI/stroke event. The uptake levels were significantly correlated with the diameter of the diseases (r = 0.748, P = 0.001 for MI and r = 0.835, P = 0.003 for stroke). Smaller or older lesions displayed no uptake.

Conclusions: (68)Ga-PRGD2 uptake was observed around the ischemic region in both MI and stroke patients, which was correlated with the disease phase and severity. The different image patterns and uptake levels in MI and stroke patients warrant further investigations.

Keywords: 68Ga-PRGD2; PET/CT; angiogenesis.; myocardial infarction; stroke; αvβ3-integrin.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Coordination Complexes* / pharmacokinetics
  • Female
  • Humans
  • Integrin alphaVbeta3 / analysis
  • Integrin alphaVbeta3 / metabolism*
  • Magnetic Resonance Angiography
  • Male
  • Middle Aged
  • Myocardial Infarction / diagnostic imaging*
  • Oligopeptides* / pharmacokinetics
  • Positron-Emission Tomography*
  • Stroke / diagnostic imaging*
  • Tomography, X-Ray Computed

Substances

  • 68Ga-1,4,7-triazacyclononane-1,4-7-triacetic acid-isothiocyanatobenzyl-c(Arg-Gly-Asp-Tyr-Lys)
  • Coordination Complexes
  • Integrin alphaVbeta3
  • Oligopeptides