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Am J Nucl Med Mol Imaging 2013;3(4):326-335
Original Article
Assessment of an elastin binding molecule for PET imaging of atherosclerotic
plaques
Cindy R Fischer, Adrienne Müller, Bianca Bochsler, Zoran Rancic, Philipp Kaufmann, Roger Schibli, Simon M Ametamey
Center for Radiopharmaceutical Sciences of ETH, PSI and USZ, Department of Chemistry and Applied Biosciences of ETH Zurich,
Wolfgang-Pauli Strasse 10, CH-8093 Zurich, Switzerland; Clinic for Cardiovascular Surgery, University Hospital Zurich, Rämistrasse
100, CH-8091 Zurich, Switzerland; Cardiac Imaging, University Hospital Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland;
Center for Radiopharmaceutical Sciences of ETH, PSI and USZ, Paul Scherrer Institute, Department Biology and Chemistry,
CH-5232 Villigen-PSI, Switzerland
Received March 6, 2013; Accepted April 22, 2013; Epub July 10, 2013; Published July 15, 2013
Abstract: Elastin is considered as a key player in human vascular diseases and it might contribute to the development of
atherosclerosis. The elastin binding radiotracer, [18F]AlF-NOTA-EBM ([18F]2), was evaluated in a wild type mouse to determine its in
vivo distribution and on human carotid atherosclerotic plaque tissues to assess its utility as a PET imaging agent for visualizing
human atherosclerotic plaque lesions. The free ligand NOTA-EBM, which served as the precursor, was obtained in 25% chemical
yield. The radiosynthesis of [18F]2 was accomplished by coordination of Al18F to NOTA-EBM in 8-13% decay corrected
radiochemical yield (n = 7) and specific radioactivity of 59 ± 12 GBq/µmol. A dynamic in vivo PET scan in a healthy wild type mouse
(C57BL/6) showed high accumulation of radioactivity in heart and lungs, organs reported to have high elastin content. Excretion of
[18F]2 proceeded via the renal pathway and through the hepatobiliary system as indicated by a high uptake of radioactivity in the liver,
intestines and gall bladder. In vitro autoradiography on human atherosclerotic plaque sections showed a heterogeneous distribution
of [18F]2 with an elevated accumulation in stable and vulnerable atherosclerotic plaques compared to control samples of normal
arteries. However, there was no statistical significance between the different plaque phenotypes and control samples. Competition
experiments with 10.000-fold excess of free ligand NOTA-EBM resulted in a marked decrease of radioactivity accumulation,
consistent with a target-specific ligand. (ajnmmi1303003).
Keywords: Elastin, atherosclerotic plaques, PET imaging, autoradiography, Al18F
Address correspondence to: Dr. Simon M Ametamey, Center for Radiopharmaceutical Sciences of ETH, PSI and USZ, Department
of Chemistry and Applied Biosciences of ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland. Tel: +41 44 633 74 63;
Fax: +41 44 633 13 67; E-mail: Simon.Ametamey@pharma.ethz.ch
Original Article
Assessment of an elastin binding molecule for PET imaging of atherosclerotic
plaques
Cindy R Fischer, Adrienne Müller, Bianca Bochsler, Zoran Rancic, Philipp Kaufmann, Roger Schibli, Simon M Ametamey
Center for Radiopharmaceutical Sciences of ETH, PSI and USZ, Department of Chemistry and Applied Biosciences of ETH Zurich,
Wolfgang-Pauli Strasse 10, CH-8093 Zurich, Switzerland; Clinic for Cardiovascular Surgery, University Hospital Zurich, Rämistrasse
100, CH-8091 Zurich, Switzerland; Cardiac Imaging, University Hospital Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland;
Center for Radiopharmaceutical Sciences of ETH, PSI and USZ, Paul Scherrer Institute, Department Biology and Chemistry,
CH-5232 Villigen-PSI, Switzerland
Received March 6, 2013; Accepted April 22, 2013; Epub July 10, 2013; Published July 15, 2013
Abstract: Elastin is considered as a key player in human vascular diseases and it might contribute to the development of
atherosclerosis. The elastin binding radiotracer, [18F]AlF-NOTA-EBM ([18F]2), was evaluated in a wild type mouse to determine its in
vivo distribution and on human carotid atherosclerotic plaque tissues to assess its utility as a PET imaging agent for visualizing
human atherosclerotic plaque lesions. The free ligand NOTA-EBM, which served as the precursor, was obtained in 25% chemical
yield. The radiosynthesis of [18F]2 was accomplished by coordination of Al18F to NOTA-EBM in 8-13% decay corrected
radiochemical yield (n = 7) and specific radioactivity of 59 ± 12 GBq/µmol. A dynamic in vivo PET scan in a healthy wild type mouse
(C57BL/6) showed high accumulation of radioactivity in heart and lungs, organs reported to have high elastin content. Excretion of
[18F]2 proceeded via the renal pathway and through the hepatobiliary system as indicated by a high uptake of radioactivity in the liver,
intestines and gall bladder. In vitro autoradiography on human atherosclerotic plaque sections showed a heterogeneous distribution
of [18F]2 with an elevated accumulation in stable and vulnerable atherosclerotic plaques compared to control samples of normal
arteries. However, there was no statistical significance between the different plaque phenotypes and control samples. Competition
experiments with 10.000-fold excess of free ligand NOTA-EBM resulted in a marked decrease of radioactivity accumulation,
consistent with a target-specific ligand. (ajnmmi1303003).
Keywords: Elastin, atherosclerotic plaques, PET imaging, autoradiography, Al18F
Address correspondence to: Dr. Simon M Ametamey, Center for Radiopharmaceutical Sciences of ETH, PSI and USZ, Department
of Chemistry and Applied Biosciences of ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland. Tel: +41 44 633 74 63;
Fax: +41 44 633 13 67; E-mail: Simon.Ametamey@pharma.ethz.ch
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