Assessment of an elastin binding molecule for PET imaging of atherosclerotic plaques

American Journal of Nuclear Medicine and Molecular Imaging

Cindy R Fischer¹  Bianca Bochsler¹  Philipp Kaufmann¹  Zoran Rancic¹  Adrienne Müller¹  Simon M Ametamey¹  Roger Schibli¹ 

关键词: Elastin;    atherosclerotic plaques;    PET imaging;    autoradiography;    Al18F;   

DOI  :  

学科分类：过敏症与临床免疫学

来源: e-Century Publishing Corporation

【 摘 要 】

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.

【 授权许可】

Unknown