Antibodies against adherent native LDL have potential as molecular targeting agents for imaging of and therapeutic delivery to atherosclerosis. Furthermore, in vivo near-infrared fluorescence molecular tomographic imaging and ex vivo confocal microscopy showed that intravenously injected LO9 localized beneath endothelium of the aortic arch in Ldlr-/- mice, in the vicinity of macrophages.Conclusions We believe LO9 is the first example of an IgG autoantibody that reacts with a native LDL epitope revealed by adherence to tissue matrix. LO9 reacted with antigen in mouse atherosclerosis and in both human stable and ruptured coronary atherosclerosis. We localized the epitope to a 20 amino-acid peptide sequence (P5) in the globular amino-terminus of apolipoprotein B. LO9 binding to immobilized native LDL was not neutralized by fluid-phase native LDL, indicating an adhesion-dependent epitope. Objectives We aimed to generate and characterize IgG monoclonal autoantibodies in atherosclerosis for targeting of novel molecular determinants.Background Antibody-based constructs for molecular imaging and therapeutic delivery provide promising opportunities for the diagnosis and treatment of atherosclerosis.Methods We created hybridomas from an unimmunized LDL receptor-deficient (Ldlr-/-) mouse and selected an IgG2b isotype autoantibody, LO9, for further characterization.Results LO9 reacted well with native LDL bound to immobilized matrix components, and less well to oxidized LDL. Pandey S, Marceddu C, Kojima C, Chang S-H, Boyle JJ, Johnson JL, Björkbacka H, Guo L, Finn AV, Virmani R, Nilsson J, Haskard D et al., 2022, A monoclonal autoantibody against a cryptic epitope on tissue-adherent low-density lipoprotein for molecular imaging in atherosclerosis, JACC: Cardiovascular Imaging, Vol: 15, ISSN: 1876-7591 The recommendations made in this Consensus Statement will help clinicians to choose the most appropriate imaging mo Finally, intravascular ultrasonography and optical coherence tomography are the most important invasive imaging modalities for the identification of plaques at high risk of rupture. Invasive coronary angiography is the reference standard for stenosis assessment but cannot characterize coronary plaques. PET has the greatest potential for quantifying inflammation in coronary plaque but SPECT currently has a limited role in clinical coronary artery stenosis and atherosclerosis imaging. According to the Delphi survey answers, CT is the method of choice to rule out obstructive stenosis in patients with an intermediate pre-test probability of coronary artery disease and enables quantitative assessment of coronary plaque with respect to dimensions, composition, location and related risk of future cardiovascular events, whereas MRI facilitates the visualization of coronary plaque and can be used in experienced centres as a radiation-free, second-line option for non-invasive coronary angiography. Clinical consensus recommendations on the appropriateness of each imaging technique for direct coronary artery visualization were derived through a three-step, real-time Delphi process that took place before, during and after the Second International Quantitative Cardiovascular Imaging Meeting in September 2022. In this Consensus Statement, we provide clinical consensus recommendations on the optimal use of different imaging techniques in various patient populations and describe the advances in imaging technology. In this regard, imaging-based quantification can be improved by choosing the most appropriate imaging modality for diagnosis, treatment and procedural planning. The detection and characterization of coronary artery stenosis and atherosclerosis using imaging tools are key for clinical decision-making in patients with known or suspected coronary artery disease. Alkadhi H, Hajhosseiny R, Maurovich-Horvat P, Manka R, Kozerke S, Stuber M, Derlin T, Channon KM, Išgum I, Coenen A, Foellmer B, Dey D, Volleberg RHJA, Meinel FG, Dweck MR, Piek JJ, van de Hoef T, Landmesser U, Guagliumi G, Giannopoulos AA, Botnar RM, Khamis R, Williams MC, Newby DE, Dewey M et al., 2023, Clinical quantitative coronary artery stenosis and coronary atherosclerosis imaging: a Consensus Statement from the Quantitative Cardiovascular Imaging Study Group., Nat Rev Cardiol
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