title: Multi-slice computed tomography with N1177 identifies ruptured atherosclerotic plaques in rabbits.
abstract: Rupture-prone and ruptured plaques are characterized by the presence of large numbers of macrophages. N1177 is a contrast agent consisting of iodinated nanoparticles that are selectively phagocytosed by macrophages. The aim of this study was to investigate the effect of N1177 on the CT attenuation of rupture-prone and ruptured plaques in rabbits. In addition, we examined in vitro whether uptake of N1177 occurred without cytotoxic or pro-inflammatory effects on macrophages. In vitro, the viability of J774 macrophages was not affected by treatment with N1177. Moreover, N1177 had no effect on the phagocytic capacity or cytokine production of macrophages. For the in vivo experiments, 6 New Zealand White rabbits were fed a cholesterol-supplemented diet for 12-15 months, resulting in the development of large atherosclerotic plaques that resembled rupture-prone plaques in humans. In three rabbits, mechanical plaque rupture was induced by retrograde pullback of an embolic protection device. N1177 had no effect on the median density of rupture-prone plaques [35 HU (range 3-85) before injection vs. 32 HU (range 1-93) 2 h after injection of N1177; P > 0.05]. However, after induction of mechanical plaque rupture, the median density of the atherosclerotic plaques increased from 40 HU (range 6-86) before injection to 74 HU (range 14-111) 2 h after injection of N1177 (P < 0.001). Using time-of-flight static secondary ion mass spectrometry, the presence of N1177 nanoparticles was demonstrated in macrophage-rich areas of ruptured plaques, but not of non-ruptured plaques. In conclusion, our results show that N1177 is a contrast agent that can identify ruptured atherosclerotic plaques.
authors.affiliation: Division of Cardiology, Antwerp University Hospital, Wilrijkstraat 10, 2650, Edegem, Belgium. jozef.vanherck@ua.ac.be
authors.forename: Jozef Leo
authors.initials: JL
authors.lastname: Van Herck
authors.forename: Guido R Y
authors.initials: GR
authors.lastname: De Meyer
authors.forename: Wim
authors.initials: W
authors.lastname: Martinet
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Salgado
authors.forename: Bharati
authors.initials: B
authors.lastname: Shivalkar
authors.forename: Roel
authors.initials: R
authors.lastname: De Mondt
authors.forename: Helene
authors.initials: H
authors.lastname: Van De Ven
authors.forename: Annick
authors.initials: A
authors.lastname: Ludwig
authors.forename: Pieter
authors.initials: P
authors.lastname: Van Der Veken
authors.forename: Luc
authors.initials: L
authors.lastname: Van Vaeck
authors.forename: Hidde
authors.initials: H
authors.lastname: Bult
authors.forename: Arnold G
authors.initials: AG
authors.lastname: Herman
authors.forename: Christiaan J
authors.initials: CJ
authors.lastname: Vrints
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000000981:diagnostic imaging*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003287:Contrast Media / Q000009:adverse effects; D007455:Iodine; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D053758:Nanoparticles; D011817:Rabbits; D012422:Rupture, Spontaneous / Q000000981:diagnostic imaging; D014057:Tomography, X-Ray Computed
chemical_list: D003287:Contrast Media; D007455:Iodine