A dual-labeled cRGD-based PET/optical tracer for pre-operative staging and intraoperative treatment of colorectal cancer.

Autor: Sibinga Mulder BG; Department of Surgery, Leiden University Medical Center Leiden, The Netherlands., Handgraaf HJ; Department of Surgery, Leiden University Medical Center Leiden, The Netherlands., Vugts DJ; Department of Nuclear Medicine, VU Medical Center Amsterdam, The Netherlands., Sewing C; Department of Nuclear Medicine, VU Medical Center Amsterdam, The Netherlands., Windhorst AD; Department of Nuclear Medicine, VU Medical Center Amsterdam, The Netherlands., Stammes M; Department of Radiology, Leiden University Medical Center Leiden, The Netherlands., de Geus-Oei LF; Department of Nuclear Medicine, Leiden University Medical Center Leiden, The Netherlands.; Biomedical Photonic Imaging Group, University of Twente Enschede, The Netherlands., Bordo MW; Curadel, LLC Marlborough, MA, U.S.A., Mieog JSD; Department of Surgery, Leiden University Medical Center Leiden, The Netherlands., van de Velde CJ; Department of Surgery, Leiden University Medical Center Leiden, The Netherlands., Frangioni JV; Curadel, LLC Marlborough, MA, U.S.A., Vahrmeijer AL; Department of Surgery, Leiden University Medical Center Leiden, The Netherlands.
Jazyk: angličtina
Zdroj: American journal of nuclear medicine and molecular imaging [Am J Nucl Med Mol Imaging] 2018 Oct 20; Vol. 8 (5), pp. 282-291. Date of Electronic Publication: 2018 Oct 20 (Print Publication: 2018).
Abstrakt: cRGD peptides target integrins associated with angiogenesis (e.g., α v β 3 ) and cancer, and have been used as binding ligands for both positron emission tomography (PET) and near-infrared fluorescence (NIRF) optical imaging. This study introduces the hybrid tracer cRGD-ZW800-1-Forte-[ 89 Zr]Zr-DFO, which is based on a novel zwitterionic fluorophore structure that reduces non-specific background uptake during molecular imaging of tumors. An in vitro binding assay was used to validate tracer performance. 10 nmol ZW800F-cRGD-Zr-DFO was injected in mice (n=7) bearing orthotopic human colorectal tumors (HT29-luc2) for tumor detection with NIRF imaging. Subsequently, ZW800F-cRGD-Zr-DFO was loaded with 89 Zr and 10 nmol cRGD-ZW800-1-Forte-[ 89 Zr]Zr-DFO (3 MBq) was injected in mice (n=8) for PET/CT imaging. Imaging and biodistribution was performed at 4 and 24 h. NIRF imaging was performed up to 168 h after administration. Sufficient fluorescent signals were measured in the tumors of mice injected with ZW800F-cRGD-Zr-DFO (emission peak ~800 nm) compared to the background. The signal remained stable for up to 7 days. The fluorescence signal of cRGD-ZW800-1-Forte-[ 89 Zr]Zr-DFO remained intact after labeling with 89 Zr. PET/CT permitted clear visualization of the colorectal tumors at 4 and 24 h. Biodistribution at 4 h showed the highest uptake of the tracer in kidneys and sufficient uptake in the tumor, remaining stable for up to 24 h. A single molecular imaging agent, ZW800F-cRGD-[ 89 Zr]Zr-DFO, permits serial PET and NIRF imaging of colorectal tumors, with the latter permitting image-guided treatment intraoperatively. Due to its unique zwitterionic structure, the tracer is rapidly renally cleared and fluorescent background signals are low.
Competing Interests: John V. Frangioni is currently CEO of Curadel, Curadel ResVet Imaging, and Curadel Surgical Innovations, which are for-profit companies that have licensed FLARE® technology from Beth Israel Deaconess Medical Center. All other authors have no conflicts of interests or financial ties to disclose.
Databáze: MEDLINE
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