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

Autor: Vahrmeijer, Alexander L., Frangioni, John, Velde, Cornelis J. H., Mieog, J. Sven D., Bordo, Mark W., Lioe-Fee de Geus-Oei, Stammes, Marieke, Windhorst, Albert D., Sewing, Claudia, Vugts, Danielle J., Handgraaf, Henricus J. M., Mulder, Babs G. Sibinga
Přispěvatelé: Radiology and nuclear medicine, CCA - Imaging and biomarkers
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Publons
American journal of nuclear medicine and molecular imaging, 8(5), 282-291. e-Century Publishing Corporation
Sibinga Mulder, B G, Handgraaf, H J, Vugts, D J, Sewing, C, Windhorst, A D, Stammes, M, de Geus-Oei, L-F, Bordo, M W, Mieog, J S D, van de Velde, C J, Frangioni, J V & Vahrmeijer, A L 2018, ' A dual-labeled cRGD-based PET/optical tracer for pre-operative staging and intraoperative treatment of colorectal cancer ', American journal of nuclear medicine and molecular imaging, vol. 8, no. 5, pp. 282-291 .
ISSN: 2160-8407
Popis: cRGD peptides target integrins associated with angiogenesis (e.g., αvβ3) 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-[89Zr]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 89Zr and 10 nmol cRGD-ZW800-1-Forte-[89Zr]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-[89Zr]Zr-DFO remained intact after labeling with 89Zr. 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-[89Zr]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.
Databáze: OpenAIRE