Application of ⁶⁸Ga-PRGD2 PET/CT for α_vβ₃-integrin Imaging of Myocardial Infarction and Stroke

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 68Ga-S-2-(isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid-PEG3-E[c(RGDyK)]2 (68Ga-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 68Ga-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 68Ga-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 68Ga-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: 68Ga-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.

SPECT and PET imaging of angiogenesis and arteriogenesis in pre-clinical models of myocardial ischemia and peripheral vascular disease

“…The feasibility of clinical angiogenesis imaging through targeting the α v β 3 integrin was further shown in studies by Mozid et al [111] and Sun et al [112]. Mozid and co-workers applied an intracoronary injection of granulocyte colony-stimulating factor mobilized bone-marrow stem cells in patients with chronic ischemic heart failure.…”

“…As in pre-clinical research, the main target for imaging has been the α v β 3 integrin through various radiolabeled RGD peptides [99–106], while the VEGF receptor [107], prostate-specific membrane antigen (PSMA) [108], and the extra domain B of fibronectin [109] have also received attention. To date, only a few small studies in MI patients have been performed, all using the α v β 3 integrin as a target for angiogenesis imaging [110–112] (Table 2). …”

“…To date, only a few small studies in MI patients have been performed, all using the α v β 3 integrin as a target for angiogenesis imaging [110–112] (Table 2). …”

“…Sun and co-workers used 68 Ga-PRGD2 SPECT in MI and stroke patients and found enhanced uptake in 20 out of 23 MI patients and in eight out of 16 stroke patients. Furthermore, higher uptake of 68 Ga-PRGD2 was observed 1–3 weeks after the onset of MI/stroke and correlated well with the disease phase and severity [112]. …”

Comparing the Diagnostic Potential of 68Ga-Alfatide II and 18F-FDG in Differentiating Between Non–Small Cell Lung Cancer and Tuberculosis

“…68 Ga-Alfatide II and 18 F-FDG were injected intravenously with a dosage of 1.85 MBq/kg (0.05 mCi/kg) and 5.55 MBq/kg (0.15 mCi/kg), respectively. The dosage was determined on the basis of previous clinical trials (19,20). Wholebody PET imaging was acquired 60 min after the injection of tracers.…”