4.8 Article

Application of 68Ga-PRGD2 PET/CT for αvβ3-integrin Imaging of Myocardial Infarction and Stroke

Journal

THERANOSTICS
Volume 4, Issue 8, Pages 778-786

Publisher

IVYSPRING INT PUBL
DOI: 10.7150/thno.8809

Keywords

Ga-68-PRGD2; PET/CT; stroke; myocardial infarction; alpha(v)beta(3)-integrin; angiogenesis

Funding

  1. Major State Basic Research Development Program of China (973 Program) [2013CB733802, 2014CB744503]
  2. National Natural Science Foundation of China [81171370, 81271614, 81371596, 30870725]
  3. Capital Special Project for Featured Clinical Application [Z121107001012119]
  4. Peking Union Medical College Hospital [PUMCH-2013-011]
  5. Intramural Research Program (IRP), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH)

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Purpose: Ischemic vascular diseases, including myocardial infarction (MI) and stroke, have been found to be associated with elevated expression of alpha(v)beta(3)-integrin, which provides a promising target for semi-quantitative monitoring of the disease. For the first time, we employed Ga-68-S-2-(isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid-PEG3-E[c(RGDyK)](2) (Ga-68-PRGD2) to evaluate the alpha(v)beta(3)-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 Ga-68-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 Ga-68-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 Ga-68-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: Ga-68-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.

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