Effect of Dye and Conjugation Chemistry on the Biodistribution Profile of Near-Infrared-Labeled Nanobodies as Tracers for Image-Guided Surgery

Autor: Sam Massa, Pieterjan Debie, Sophie Hernot, Inge Hansen, Jannah Van Quathem, Catarina Xavier, Gezim Bala, Nick Devoogdt
Přispěvatelé: Supporting clinical sciences, Faculty of Medicine and Pharmacy, Medical Imaging, Pathology/molecular and cellular medicine, Cardio-vascular diseases, Cellular and Molecular Immunology, Translational Imaging Research Alliance, Clinical sciences
Rok vydání: 2017
Předmět:
0301 basic medicine
Biodistribution
Tumor targeting
Spectroscopy
Near-Infrared/methods
Indoles
Nanoparticles/metabolism
Receptor
ErbB-2
Receptor
ErbB-2/metabolism
Pharmaceutical Science
Mice
Nude
Nanotechnology
CHO Cells
Conjugated system
Cell Line
03 medical and health sciences
Mice
Optical imaging
Cricetulus
Benzenesulfonates/administration & dosage
Cell Line
Tumor
Neoplasms
Drug Discovery
Animals
Tissue Distribution
Tissue Distribution/drug effects
Spectroscopy
Near-Infrared
Chemistry
Surgery
Computer-Assisted/methods
Near-infrared spectroscopy
Benzenesulfonates
Indoles/administration & dosage
Single-Domain Antibodies
Single-Domain Antibodies/metabolism
Molecular Imaging
030104 developmental biology
Image-guided surgery
Surgery
Computer-Assisted
Biophysics
Molecular Medicine
Nanoparticles
Molecular Imaging/methods
Female
Molecular imaging
Preclinical imaging
Neoplasms/diagnosis
Zdroj: ResearcherID
ISSN: 1543-8392
Popis: Advances in optical imaging technologies have stimulated the development of near-infrared (NIR) fluorescently labeled targeted probes for use in image-guided surgery. As nanobodies have already proven to be excellent candidates for molecular imaging, we aimed in this project to design NIR-conjugated nanobodies targeting the tumor biomarker HER2 for future applications in this field and to evaluate the effect of dye and dye conjugation chemistry on their pharmacokinetics during development. IRDye800CW or IRdye680RD were conjugated either randomly (via lysines) or site-specifically (via C-terminal cysteine) to the anti-HER2 nanobody 2Rs15d. After verification of purity and functionality, the biodistribution and tumor targeting of the NIR-nanobodies were assessed in HER2-positive and -negative xenografted mice. Site-specifically IRDye800CW- and IRdye680RD-labeled 2Rs15d as well as randomly labeled 2Rs15d-IRDye680RD showed rapid tumor accumulation and low nonspecific uptake, resulting in high tumor-to-muscle ratios at early time points (respectively 6.6 ± 1.0, 3.4 ± 1.6, and 3.5 ± 0.9 for HER2-postive tumors at 3 h p.i., while1.0 for HER2-negative tumors at 3 h p.i., p0.05). Contrarily, using the randomly labeled 2Rs15d-IRDye800CW, HER2-positive and -negative tumors could only be distinguished after 24 h due to high nonspecific signals. Moreover, both randomly labeled 2Rs15d nanobodies were not only cleared via the kidneys but also partially via the hepatobiliary route. In conclusion, near-infrared fluorescent labeling of nanobodies allows rapid, specific, and high contrast in vivo tumor imaging. Nevertheless, the fluorescent dye as well as the chosen conjugation strategy can affect the nanobodies' properties and consequently have a major impact on their pharmacokinetics.
Databáze: OpenAIRE
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