Thorsten Derlin1, Johannes Thiele2, Desiree Weiberg2, James T Thackeray2, Klaus Püschel2, Hans-Jürgen Wester2, Lukas Aguirre Dávila2, Axel Larena-Avellaneda2, Günter Daum2, Frank M Bengel2, Udo Schumacher2. 1. From the Department of Nuclear Medicine (T.D., J.T., D.W., J.T.T., F.M.B.) and Institute of Biometry (L.A.D.), Hannover Medical School, Germany; Institute of Legal Medicine (K.P.) and Institute of Anatomy and Experimental Morphology (U.S.), University Medical Center Hamburg-Eppendorf, Germany; Radiopharmaceutical Chemistry, Technical University Munich, Garching, Germany (H.-J.W.); and Department of Vascular Medicine, University Heart Center Hamburg-Eppendorf, Germany (A.L.-A., G.D.). Derlin.Thorsten@mh-hannover.de. 2. From the Department of Nuclear Medicine (T.D., J.T., D.W., J.T.T., F.M.B.) and Institute of Biometry (L.A.D.), Hannover Medical School, Germany; Institute of Legal Medicine (K.P.) and Institute of Anatomy and Experimental Morphology (U.S.), University Medical Center Hamburg-Eppendorf, Germany; Radiopharmaceutical Chemistry, Technical University Munich, Garching, Germany (H.-J.W.); and Department of Vascular Medicine, University Heart Center Hamburg-Eppendorf, Germany (A.L.-A., G.D.).
Abstract
OBJECTIVE: Intraplaque neovascularization contributes to the progression and rupture of atherosclerotic lesions. Glutamate carboxypeptidase II (GCPII) is strongly expressed by endothelial cells of tumor neovasculature and plays a major role in hypoxia-induced neovascularization in rodent models of benign diseases. We hypothesized that GCPII expression may play a role in intraplaque neovascularization and may represent a target for imaging of atherosclerotic lesions. The aim of this study was to determine frequency, pattern, and clinical correlates of vessel wall uptake of a 68Ga-GCPII ligand for positron emission tomographic imaging. APPROACH AND RESULTS: Data from 150 patients undergoing 68Ga-GCPII ligand positron emission tomography were evaluated. Tracer uptake in various arterial segments was analyzed and was compared with calcified plaque burden, cardiovascular risk factors, and immunohistochemistry of carotid specimens. Focal arterial uptake of 68Ga-GCPII ligand was identified at 5776 sites in 99.3% of patients. The prevalence of uptake sites was highest in the thoracic aorta; 18.4% of lesions with tracer uptake were colocalized with calcified plaque. High injected dose (P=0.0005) and obesity (P=0.007) were significantly associated with 68Ga-GCPII ligand accumulation, but other cardiovascular risk factors showed no association. The number of 68Ga-GCPII ligand uptake sites was significantly associated with overweight condition (P=0.0154). Immunohistochemistry did not show GCPII expression. Autoradiographic blocking studies indicated nonspecific tracer binding. CONCLUSIONS: 68Ga-GCPII ligand positron emission tomography does not identify vascular lesions associated with atherosclerotic risk. Foci of tracer accumulation are likely caused by nonspecific tracer binding and are in part noise-related. Taken together, GCPII may not be a priority target for imaging of atherosclerotic lesions.
OBJECTIVE: Intraplaque neovascularization contributes to the progression and rupture of atherosclerotic lesions. Glutamate carboxypeptidase II (GCPII) is strongly expressed by endothelial cells of tumor neovasculature and plays a major role in hypoxia-induced neovascularization in rodent models of benign diseases. We hypothesized that GCPII expression may play a role in intraplaque neovascularization and may represent a target for imaging of atherosclerotic lesions. The aim of this study was to determine frequency, pattern, and clinical correlates of vessel wall uptake of a 68Ga-GCPII ligand for positron emission tomographic imaging. APPROACH AND RESULTS: Data from 150 patients undergoing 68Ga-GCPII ligand positron emission tomography were evaluated. Tracer uptake in various arterial segments was analyzed and was compared with calcified plaque burden, cardiovascular risk factors, and immunohistochemistry of carotid specimens. Focal arterial uptake of 68Ga-GCPII ligand was identified at 5776 sites in 99.3% of patients. The prevalence of uptake sites was highest in the thoracic aorta; 18.4% of lesions with tracer uptake were colocalized with calcified plaque. High injected dose (P=0.0005) and obesity (P=0.007) were significantly associated with 68Ga-GCPII ligand accumulation, but other cardiovascular risk factors showed no association. The number of 68Ga-GCPII ligand uptake sites was significantly associated with overweight condition (P=0.0154). Immunohistochemistry did not show GCPII expression. Autoradiographic blocking studies indicated nonspecific tracer binding. CONCLUSIONS: 68Ga-GCPII ligand positron emission tomography does not identify vascular lesions associated with atherosclerotic risk. Foci of tracer accumulation are likely caused by nonspecific tracer binding and are in part noise-related. Taken together, GCPII may not be a priority target for imaging of atherosclerotic lesions.
Authors: Matthieu Dietz; Christel H Kamani; Vincent Dunet; Stephane Fournier; Vladimir Rubimbura; Nathalie Testart Dardel; Ana Schaefer; Mario Jreige; Sarah Boughdad; Marie Nicod Lalonde; Niklaus Schaefer; Nathan Mewton; John O Prior; Giorgio Treglia Journal: Front Med (Lausanne) Date: 2022-05-06
Authors: Philipp Backhaus; Benjamin Noto; Nemanja Avramovic; Lena Sophie Grubert; Sebastian Huss; Martin Bögemann; Lars Stegger; Matthias Weckesser; Michael Schäfers; Kambiz Rahbar Journal: Eur J Nucl Med Mol Imaging Date: 2018-01-15 Impact factor: 9.236