VEGF-Targeted Multispectral Optoacoustic Tomography and Fluorescence Molecular Imaging in Human Carotid Atherosclerotic Plaques
Pieter J. Steinkamp,
Jasper Vonk,
Lydian A. Huisman,
Gert-Jan Meersma,
Gilles F. H. Diercks,
Jan-Luuk Hillebrands,
Wouter B. Nagengast,
Clark J. Zeebregts,
Riemer H. J. A. Slart,
Hendrikus H. Boersma,
Gooitzen M. van Dam
Affiliations
Pieter J. Steinkamp
Department of Surgery, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands
Jasper Vonk
Department of Oral & Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands
Lydian A. Huisman
Department of Surgery, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands
Gert-Jan Meersma
Department of Pathology & Medical Biology, Pathology Division, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands
Gilles F. H. Diercks
Department of Pathology & Medical Biology, Pathology Division, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands
Jan-Luuk Hillebrands
Department of Pathology & Medical Biology, Pathology Division, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands
Wouter B. Nagengast
Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands
Clark J. Zeebregts
Department of Surgery, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands
Riemer H. J. A. Slart
Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands
Hendrikus H. Boersma
Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands
Gooitzen M. van Dam
Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands
Vulnerable atherosclerotic carotid plaques are prone to rupture, resulting in ischemic strokes. In contrast to radiological imaging techniques, molecular imaging techniques have the potential to assess plaque vulnerability by visualizing diseases-specific biomarkers. A risk factor for rupture is intra-plaque neovascularization, which is characterized by overexpression of vascular endothelial growth factor-A (VEGF-A). Here, we study if administration of bevacizumab-800CW, a near-infrared tracer targeting VEGF-A, is safe and if molecular assessment of atherosclerotic carotid plaques in vivo is possible using multispectral optoacoustic tomography (MSOT). Healthy volunteers and patients with symptomatic carotid artery stenosis scheduled for carotid artery endarterectomy were imaged with MSOT. Secondly, patients were imaged two days after intravenous administration of 4.5 bevacizumab-800CW. Ex vivo fluorescence molecular imaging of the surgically removed plaque specimen was performed and correlated with histopathology. In this first-in-human MSOT and fluorescence molecular imaging study, we show that administration of 4.5 mg bevacizumab-800CW appeared to be safe in five patients and accumulated in the carotid atherosclerotic plaque. Although we could visualize the carotid bifurcation area in all subjects using MSOT, bevacizumab-800CW-resolved signal could not be detected with MSOT in the patients. Future studies should evaluate tracer safety, higher doses of bevacizumab-800CW or develop dedicated contrast agents for carotid atherosclerotic plaque assessment using MSOT.
