Evaluation of 68Ga-Glutamate Carboxypeptidase II Ligand Positron Emission Tomography for Clinical Molecular Imaging of Atherosclerotic Plaque Neovascularization.
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 a68Ga-GCPII ligand for positron emission tomographic imaging.



Data from 150 patients undergoing68Ga-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 of68Ga-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 with68Ga-GCPII ligand accumulation, but other cardiovascular risk factors showed no association. The number of68Ga-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.



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.
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.
Thorsten
T
Derlin
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.).
Johannes
J
Thiele
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.).
Desiree
D
Weiberg
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.).
James T
JT
Thackeray
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.).
Klaus
K
Püschel
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.).
Hans-Jürgen
HJ
Wester
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.).
Lukas
L
Aguirre Dávila
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.).
Axel
A
Larena-Avellaneda
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.).
Günter
G
Daum
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.).
Frank M
FM
Bengel
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.).
Udo
U
Schumacher
D000368:Aged; D000369:Aged, 80 and over; D000954:Antigens, Surface / Q000378:metabolism*; D050197:Atherosclerosis / Q000000981:diagnostic imaging* / Q000201:enzymology / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging* / Q000201:enzymology / Q000473:pathology; D056831:Coordination Complexes / Q000493:pharmacokinetics*; D005240:Feasibility Studies; D005260:Female; D043425:Glutamate Carboxypeptidase II / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008297:Male; D008875:Middle Aged; D057054:Molecular Imaging / Q000295:instrumentation / Q000379:methods*; D009389:Neovascularization, Pathologic; D019047:Phantoms, Imaging; D058226:Plaque, Atherosclerotic; D000072078:Positron Emission Tomography Computed Tomography / Q000295:instrumentation; D011237:Predictive Value of Tests; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D015203:Reproducibility of Results; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D014018:Tissue Distribution
D000954:Antigens, Surface; D015415:Biomarkers; D056831:Coordination Complexes; D008024:Ligands; D019275:Radiopharmaceuticals; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II
PSMA; atherosclerosis; atherosclerotic plaque; physiologic neovascularization; positron-emission tomography