Activatable fluorescent cys-diabody conjugated with indocyanine green derivative: consideration of fluorescent catabolite kinetics on molecular imaging
| Autor: | Kohei Sano, Anna M. Wu, Towhid Ali, Takahito Nakajima, Chang H. Paik, Peter Choyke, Insook Kim, Hisataka Kobayashi, Derek W. Bartlett |
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| Rok vydání: | 2013 |
| Předmět: |
Glutamate Carboxypeptidase II
Indocyanine Green Biodistribution Fluorophore genetic structures Biomedical Engineering Mice Nude Polyethylene glycol Conjugated system Antibodies Polyethylene Glycols Biomaterials Mice chemistry.chemical_compound Animals Tissue Distribution Fluorescent Dyes Special Section Papers Fluorescence eye diseases Atomic and Molecular Physics and Optics Molecular Imaging Electronic Optical and Magnetic Materials Kinetics Microscopy Fluorescence chemistry Antigens Surface Biophysics Female Indocyanine green Preclinical imaging Conjugate |
| Zdroj: | Journal of Biomedical Optics. 18:101304 |
| ISSN: | 1083-3668 |
| Popis: | Antibody fragments including diabodies have more desirable pharmacokinetic characteristics than whole antibodies. An activatable optical imaging probe based on a cys-diabody targeting prostate-specific membrane antigen conjugated with the near-infrared fluorophore, indocyanine green (ICG), was designed such that it can only be activated when bound to the tumor, leading to high signal-to-background ratios. We employed short polyethylene glycol (PEG) linkers between the ICG and the reactive functional group (Sulfo-OSu group), resulting in covalent conjugation of ICG to the cys-diabody, which led to lower dissociation of ICG from cys-diabody early after injection, reducing hepatic uptake. However, unexpectedly, high and long-term fluorescence was observed in the kidneys, liver, and blood pool more than 1 h after injection of the cys-diabody PEG-ICG conjugate. A biodistribution study using I125-labeled cys-diabody-ICG showed immediate uptake in the kidneys followed by a rapid decrease, while gastric activity increased due to released radioiodine during rapid cys-diabody-ICG catabolism in the kidneys. To avoid this catabolic pathway, it would be preferable to use antibody fragments large enough not to be filtered through glomerulus or to conjugate the fragments with fluorescent dyes that are readily excreted into urine when cleaved from the cys-diabody to achieve high tumor-specific detection. |
| Databáze: | OpenAIRE |
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