Imaging angiogenesis in atherosclerosis in large arteries with 68Ga-NODAGA-RGD PET/CT: relationship with clinical atherosclerotic cardiovascular disease

Background Integrin alpha-V-beta-3 (αvβ3) pathway is involved in intraplaque angiogenesis and inflammation and represents a promising target for molecular imaging in cardiovascular diseases such as atherosclerosis. The aim of this study was to assess the clinical correlates of arterial wall accumulation of 68Ga-NODAGA-RGD, a specific αvβ3 integrin ligand for PET. Materials and methods The data of 44 patients who underwent 68Ga-NODAGA-RGD PET/CT scans were retrospectively analyzed. Tracer accumulation in the vessel wall of major arteries was analyzed semi-quantitatively by blood-pool-corrected target-to-background ratios. Tracer uptake was compared with clinically documented atherosclerotic cardiovascular disease, cardiovascular risk factors and calcified plaque burden. Data were compared using the Mann–Whitney U test, Pearson correlation and Spearman correlation. Results 68Ga-NODAGA-RGD arterial uptake was significantly higher in patients with previous clinically documented atherosclerotic cardiovascular disease (mean TBR 2.44 [2.03–2.55] vs. 1.81 [1.56–1.96], p = 0.001) and showed a significant correlation with prior cardiovascular or cerebrovascular event (r = 0.33, p = 0.027), BMI (ρ = 0.38, p = 0.01), plaque burden (ρ = 0.31, p = 0.04) and hypercholesterolemia (r = 0.31, p = 0.04). Conclusions 68Ga-NODAGA-RGD holds promise as a non-invasive marker of disease activity in atherosclerosis, providing information about intraplaque angiogenesis.

Imaging Angiogenesis in Atherosclerosis in Large Arteries with 68Ga-NODAGA-RGD PET/CT: Relationship with Clinical Atherosclerotic Cardiovascular Disease

BackgroundIntegrin alpha-V-beta-3 (αvβ3) pathway is involved in intraplaque angiogenesis and inflammation and represents a promising target for molecular imaging in cardiovascular diseases such as atherosclerosis. The aim of this study was to assess the clinical correlates of arterial wall accumulation of 68Ga-NODAGA-RGD, a specific αvβ3 integrin ligand for PET. Materials and methodsThe data of 44 patients who underwent 68Ga-NODAGA-RGD PET/CT scans were retrospectively analyzed. Tracer accumulation in the vessel wall of major arteries was analyzed semi-quantitatively by blood-pool-corrected target-to-background ratios. Tracer uptake was compared with clinically documented atherosclerotic cardiovascular disease, cardiovascular risk factors and calcified plaque burden. Data were compared using the Mann-Whitney U test and Spearman correlation. Results68Ga-NODAGA-RGD arterial uptake was significantly higher in patients with previous clinically documented atherosclerotic cardiovascular disease (mean TBR 2.44 [2.03-2.55] vs. 1.81 [1.56-1.96], p = 0.001) and showed a significant correlation with prior cardiovascular or cerebrovascular event (r = 0.34, p = 0.024), BMI (r = 0.38, p = 0.01), plaque burden (r = 0.31, p = 0.04), and hypercholesterolemia (r= 0.31, p = 0.04).Conclusions68Ga-NODAGA-RGD holds promise as a non-invasive marker of disease activity in atherosclerosis, providing information about intraplaque angiogenesis.

Esterification of 2-(4-(4-Hydroxy-3, 5-Iiodophenoxy)-3, 5-Diiodophenyl) Acetic Acid (Tetrac)

: Tetrac, a deaminated derivative of the thyroid hormome, has received some broad interest for its ability to inhibit the spread of new blood vessels, i.e., angiogenesis. For an optimum activity, the action of the dug shall be limited at the cell surface for interaction with the integrin alpha v beta 3. This was shown to be achieved via a nanoparticle formulation that would be grafted to Tetrac phenol’s OH. While the principle of this study has been disclosed elsewhere, the broad results have never been disclosed entirely. Here all outcomes of the synthesis strategy, e.g. protection and activation steps , confirmed Triisopropylsillyl as a protective group of choice to access the nanopaticle. Catalyst assisted esterification have been probed and discussed . Then a HPLC-MS study allowed to clarify reaction conditions that could subsequently yield to the desired activated Tetrac moiety. The reaction products were all characterized by 1H and 13C-NMR.

In vivo alpha-V beta-3 integrin expression in human aortic atherosclerosis

ObjectivesIntraplaque angiogenesis and inflammation are key promoters of atherosclerosis and are mediated by the alpha-V beta-3 (αvβ3) integrin pathway. We investigated the applicability of the αvβ3-integrin receptor-selective positron emission tomography (PET) radiotracer 18F-fluciclatide in assessing human aortic atherosclerosis.MethodsVascular 18F-fluciclatide binding was evaluated using ex vivo analysis of carotid endarterectomy samples with autoradiography and immunohistochemistry, and in vivo kinetic modelling following radiotracer administration. Forty-six subjects with a spectrum of atherosclerotic disease categorised as stable (n=27) or unstable (n=19; recent myocardial infarction) underwent PET and CT imaging of the thorax after administration of 229 (IQR 217–237) MBq 18F-fluciclatide. Thoracic aortic 18F-fluciclatide uptake was quantified on fused PET-CT images and corrected for blood-pool activity using the maximum tissue-to-background ratio (TBRmax). Aortic atherosclerotic burden was quantified by CT wall thickness, plaque volume and calcium scoring.Results18F-Fluciclatide uptake co-localised with regions of increased αvβ3 integrin expression, and markers of inflammation and angiogenesis. 18F-Fluciclatide vascular uptake was confirmed in vivo using kinetic modelling, and on static imaging correlated with measures of aortic atherosclerotic burden: wall thickness (r=0.57, p=0.001), total plaque volume (r=0.56, p=0.001) and aortic CT calcium score (r=0.37, p=0.01). Patients with recent myocardial infarction had greater aortic 18F-fluciclatide uptake than those with stable disease (TBRmax 1.29 vs 1.21, p=0.02).ConclusionsIn vivo expression of αvβ3 integrin in human aortic atheroma is associated with plaque burden and is increased in patients with recent myocardial infarction. Quantification of αvβ3 integrin expression with 18F-fluciclatide PET has potential to assess plaque vulnerability and disease activity in atherosclerosis.