title: Feasibility of vascular endothelial growth factor imaging in human atherosclerotic plaque using (89)Zr-bevacizumab positron emission tomography.
abstract: Intraplaque angiogenesis is associated with the occurrence of atherosclerotic plaque rupture. Cardiovascular molecular imaging can be used for the detection of rupture-prone plaques. Imaging with radiolabeled bevacizumab, a monoclonal anti-vascular endothelial growth factor (VEGF)-A, can depict VEGF levels corresponding to the angiogenic status in tumors. We determined the feasibility of 89Zr-bevacizumab imaging for the detection of VEGF in carotid endarterectomy (CEA) specimens. Five CEA specimens were coincubated with 89Zr-bevacizumab and aspecific 111In-labeled IgG to determine the specificity of bevacizumab accumulation. In 11 CEA specimens, 89Zr-bevacizumab micro-positron emission tomography (PET) was performed following 2 hours of incubation. Specimens were cut in 4 mm wide segments and were stained for VEGF and CD68. In each segment, the mean percent incubation dose per gram of tissue (%Inc/g) and tissue to background ratio were determined. A 10-fold higher accumulation of 89Zr-bevacizumab compared to 111In-IgG uptake was demonstrated by gamma counting. The mean %Inc/ghot spot was 2.2 ± 0.9 with a hot spot to background ratio of 3.6 ± 0.8. There was a significant correlation between the segmental tissue to background uptake ratio and the VEGF score (ρ  =  .74, p < .001). It is feasible to detect VEGF tissue concentration within CEA specimens using 89Zr-bevacizumab PET. 89Zr-bevacizumab accumulation in plaques is specific and correlates with immunohistochemistry scores.
authors: Departments of Nuclear Medicine and Molecular Imaging,Surgery (Divisions of Vascular and Abdominal Surgery), Clinical and Hospital Pharmacy, Medical Oncology, Cardiology, Pathology, and Gastroenterology and Hepatology, University Medical Center Groningen,University of Groningen, Groningen, the Netherlands. r.golestani@umcg.nl
authors: Reza
authors: R
authors: Golestani
authors: Clark J
authors: CJ
authors: Zeebregts
authors: Anton G T
authors: AG
authors: Terwisscha van Scheltinga
authors: Marjolijn N
authors: MN
authors: Lub-de Hooge
authors: Gooitzen M
authors: GM
authors: van Dam
authors: Andor W J M
authors: AW
authors: Glaudemans
authors: Rudi A J O
authors: RA
authors: Dierckx
authors: René A
authors: RA
authors: Tio
authors: Albert J H
authors: AJ
authors: Suurmeijer
authors: Hendrikus H
authors: HH
authors: Boersma
authors: Wouter B
authors: WB
authors: Nagengast
authors: Riemer H J A
authors: RH
authors: Slart
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000175:diagnosis*; D049268:Positron-Emission Tomography / Q000379:methods*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D015040:Zirconium
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D015040:Zirconium