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Role of Fluorophore Charge on the In Vivo Optical Imaging Properties of Near-Infrared Cyanine Dye/Monoclonal Antibody Conjugates.
- Source :
-
Bioconjugate chemistry [Bioconjug Chem] 2016 Feb 17; Vol. 27 (2), pp. 404-13. Date of Electronic Publication: 2015 Oct 23. - Publication Year :
- 2016
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Abstract
- Near-infrared (NIR) fluorophores have several advantages over visible-light fluorophores, including superior light penetration in tissue and lower autofluorescence. We recently demonstrated that a new class of NIR cyanine dyes containing a novel C4'-O-alkyl linker exhibit greater chemical stability and excellent optical properties relative to existing C4'-O-aryl variants. We synthesized two NIR cyanine dyes with the same core structure but different indolenine substituents: FNIR-774 bearing four sulfonate groups and FNIR-Z-759 bearing a combination of two sulfonates and two quaternary ammonium cations, resulting in an anionic (-3) or monocationic (+1) charge, respectively. In this study, we compare the in vitro and in vivo optical imaging properties of monoclonal antibody (mAb) conjugates of FNIR-774 and FNIR-Z-759 with panitumumab (pan) at antibody-to-dye ratios of 1:2 or 1:5. Conjugates of both dyes demonstrated similar quenching capacity, stability, and brightness in target cells in vitro. However, FNIR-Z-759 conjugates showed significantly lower background in mice, resulting in higher tumor-to-background ratio. Thus, FNIR-Z-759 conjugates appear to have superior in vivo imaging characteristics compared with FNIR-774 conjugates, especially in the abdominal region, regardless of the dye-mAb ratio. These results suggest that zwitterionic cyanine dyes are a promising class of fluorophores for improving in vivo optical imaging with antibody-NIR dye conjugates.
- Subjects :
- Animals
Antibodies, Monoclonal pharmacokinetics
Carbocyanines pharmacokinetics
Cell Line, Tumor
Female
Fluorescent Dyes pharmacokinetics
Humans
Immunoconjugates pharmacokinetics
Mice
Mice, Nude
Microscopy, Fluorescence
Panitumumab
Quaternary Ammonium Compounds chemistry
Quaternary Ammonium Compounds pharmacokinetics
Sulfonic Acids chemistry
Sulfonic Acids pharmacokinetics
Antibodies, Monoclonal chemistry
Carbocyanines chemistry
Fluorescent Dyes chemistry
Immunoconjugates chemistry
Neoplasms diagnosis
Optical Imaging
Subjects
Details
- Language :
- English
- ISSN :
- 1520-4812
- Volume :
- 27
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Bioconjugate chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 26444497
- Full Text :
- https://doi.org/10.1021/acs.bioconjchem.5b00492