title: Impact of Substituents in Tumor Uptake and Fluorescence Imaging Ability of Near-Infrared Cyanine-like Dyes.
abstract: This report presents a simple strategy to introduce various functionalities in a cyanine dye (bis-indole-N-butylsulfonate-polymethine bearing a fused cyclic chloro-cyclohexene ring structure), and assess the impact of these substitutions in tumor uptake, retention and imaging. The results obtained from the structural activity relationship (SAR) study demonstrate that certain structural features introduced in the cyanine dye moiety make a remarkable difference in tumor avidity. Among the compounds investigated, the symmetrical CDs containing an amino-phenyl thioether group attached to a cyclohexene ring system and the two N-butyl linkers with terminal sulfonate groups in benzoindole moieties exhibited excellent tumor imaging ability in BALB/c mice bearing Colon26 tumors. Compared to indocyanine green (ICG), approved by FDA as a blood pooling agent, which has also been investigated for the use in tumor imaging, the modified CD selected on the basis of SAR study produced enhanced uptake and longer retention in tumor(s). A facile approach reported herein for introducing a variety of functionalities in tumor-avid CD provides an opportunity to create multi-imaging modality agent(s). Using a combination of mass spectrometry and absorbance techniques, the photobleaching of one of the CDs was analyzed and significant regioselective photooxidation was observed.
authors.affiliation: Department of Molecular Pharmacology and Cancer Therapeutics, Cell Stress Biology Roswell Park Cancer Institute, Buffalo, NY.|PDT Center, Cell Stress Biology Roswell Park Cancer Institute, Buffalo, NY.
authors.forename: Nayan J
authors.initials: NJ
authors.lastname: Patel
authors.affiliation: PDT Center, Cell Stress Biology Roswell Park Cancer Institute, Buffalo, NY.
authors.forename: Ethirajan
authors.initials: E
authors.lastname: Manivannan
authors.affiliation: PDT Center, Cell Stress Biology Roswell Park Cancer Institute, Buffalo, NY.
authors.forename: Penny
authors.initials: P
authors.lastname: Joshi
authors.affiliation: Institute for Lasers, Photonics and Biophotonics SUNY at Buffalo, Buffalo, NY.
authors.forename: Tymish J
authors.initials: TJ
authors.lastname: Ohulchanskyy
authors.affiliation: Chemical Biology Laboratory, National Cancer Institute, National Institutes of Health, Frederick, MD.
authors.forename: Roger R
authors.initials: RR
authors.lastname: Nani
authors.affiliation: Chemical Biology Laboratory, National Cancer Institute, National Institutes of Health, Frederick, MD.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Schnermann
authors.affiliation: Department of Molecular Pharmacology and Cancer Therapeutics, Cell Stress Biology Roswell Park Cancer Institute, Buffalo, NY.|PDT Center, Cell Stress Biology Roswell Park Cancer Institute, Buffalo, NY.
authors.forename: Ravindra K
authors.initials: RK
authors.lastname: Pandey
mesh_terms: D000818:Animals; D002232:Carbocyanines / Q000737:chemistry* / Q000378:metabolism*; D045744:Cell Line, Tumor; D004298:Dopamine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007259:Infrared Rays; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D009369:Neoplasms / Q000503:physiopathology; D061848:Optical Imaging; D013329:Structure-Activity Relationship
chemical_list: D002232:Carbocyanines; C574569:dopamine-heptamethine cyanine dye; D004298:Dopamine