Correlating molecular character of NIR imaging agents with tissue-specific uptake.
Near-infrared (NIR) fluorescent contrast agents are emerging in optical imaging as sensitive, cost-effective, and nonharmful alternatives to current agents that emit harmful ionizing radiation. Developing spectrally distinct NIR fluorophores to visualize sensitive vital tissues to selectively avoid them during surgical resection of diseased tissue is of great significance. Herein, we report the synthetic variation of pentamethine cyanine fluorophores with modifications of physicochemical properties toward prompting tissue-specific uptake into sensitive tissues (i.e., endocrine glands). Tissue-specific targeting and biodistribution studies revealed localization of contrast agents in the adrenal and pituitary glands, pancreas, and lymph nodes with dependence on molecular characteristics. Incorporation of hydrophobic heterocyclic rings, alkyl groups, and halogens allowed a fine-tuning capability to the hydrophobic character and dipole moment for observing perturbation in biological activity in response to minor structural alterations. These NIR contrast agents have potential for clinical translation for intraoperative imaging in the delineation of delicate glands.
†Center for Diagnostics and Therapeutics, Center for Biotechnology and Drug Design, Department of Chemistry, Georgia State University, Petit Science Center, 100 Piedmont Ave SE, Atlanta, Georgia 30303, United States.
Eric A
EA
Owens
‡Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, 330 Brookline Avenue, Massachusetts 02215, United States.
Hoon
H
Hyun
†Center for Diagnostics and Therapeutics, Center for Biotechnology and Drug Design, Department of Chemistry, Georgia State University, Petit Science Center, 100 Piedmont Ave SE, Atlanta, Georgia 30303, United States.
Joseph G
JG
Tawney
‡Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, 330 Brookline Avenue, Massachusetts 02215, United States.
Hak Soo
HS
Choi
†Center for Diagnostics and Therapeutics, Center for Biotechnology and Drug Design, Department of Chemistry, Georgia State University, Petit Science Center, 100 Piedmont Ave SE, Atlanta, Georgia 30303, United States.
Maged
M
Henary
D000818:Animals; D060326:Chemistry Techniques, Synthetic; D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics*; D004702:Endocrine Glands / Q000187:drug effects; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D007432:Intraoperative Period; D008198:Lymph Nodes / Q000187:drug effects; D008297:Male; D008815:Mice, Inbred Strains; D061848:Optical Imaging / Q000379:methods*; D013053:Spectrophotometry / Q000379:methods; D013329:Structure-Activity Relationship; D034421:Sus scrofa; D014018:Tissue Distribution
D003287:Contrast Media; D005456:Fluorescent Dyes