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Assessment of an elastin binding molecule for PET imaging of atherosclerotic plaques - Zurich Open Repository and Archive


Fischer, Cindy R; Müller, Adrienne; Bochsler, Bianca; Rancic, Zoran; Kaufmann, Philipp; Schibli, Roger; Ametamey, Simon M (2013). Assessment of an elastin binding molecule for PET imaging of atherosclerotic plaques. American Journal of Nuclear Medicine and Molecular Imaging, 3(4):326-335.

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, [(18)F]AlF-NOTA-EBM ([(18)F]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 [(18)F]2 was accomplished by coordination of Al(18)F 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 [(18)F]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 [(18)F]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.

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, [(18)F]AlF-NOTA-EBM ([(18)F]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 [(18)F]2 was accomplished by coordination of Al(18)F 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 [(18)F]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 [(18)F]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.

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Additional indexing

Item Type:Journal Article, not refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Nuclear Medicine
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2013
Deposited On:17 Oct 2013 10:25
Last Modified:04 Aug 2017 00:57
Publisher:e-Century Publishing Corporation
ISSN:2160-8407
Free access at:PubMed ID. An embargo period may apply.
Official URL:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3715777/
PubMed ID:23901358

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