TY - JOUR
T1 - Nile Red derivatives enable improved ratiometric imaging for nerve-specific contrast
AU - Korber, Jesse R.
AU - Barth, Connor W.
AU - Gibbs, Summer L.
N1 - Funding Information:
We would like to thank Sarah Cook and Evan Muschler for experimental assistance. This work was funded by the National Cancer Institute (R01CA188491) and the National Institute for Biomedical Imaging and Bioengineering (R01EB021362).
Publisher Copyright:
© 2018 Society of Photo-Optical Instrumentation Engineers (SPIE).
PY - 2018/7/1
Y1 - 2018/7/1
N2 - Surgical nerve damage due to difficulty with identification remains a major risk for postsurgical complications and decreased quality of life. Fluorescence-guided surgery offers a means to specifically highlight tissues of interest such as nerves and a number of fluorescence-guided surgical systems are in clinical trial or are approved for clinical use. However, no clinically approved nerve-specific fluorophores exist. In addition, many preclinical nerve-specific fluorophores tend to accumulate in adipose tissue due to the molecular composition similarities between the two tissues, making it challenging to generate a specific nerve signal. To alleviate this difficulty, we have synthesized a library of oxazine fluorophores based on the Nile Red scaffold, with the goal of strong adipose specificity without nerve uptake to facilitate ratiometric imaging. The library was screened for tissue specificity ex vivo and in vivo, enabling quantification of adipose-, nerve- and muscle-specific uptake as well as selection of the best candidate for adipose selectivity without nerve signal. We showed our selected Nile Red fluorophore improved nerve contrast using ratiometric imaging, especially nerve-to-adipose contrast as compared to the parent Nile Red compound or nerve-specific imaging alone. This adipose-specific Nile Red derivative could be used in future fluorescence-guided surgery applications where adipose- or nerve-specific contrast is required.
AB - Surgical nerve damage due to difficulty with identification remains a major risk for postsurgical complications and decreased quality of life. Fluorescence-guided surgery offers a means to specifically highlight tissues of interest such as nerves and a number of fluorescence-guided surgical systems are in clinical trial or are approved for clinical use. However, no clinically approved nerve-specific fluorophores exist. In addition, many preclinical nerve-specific fluorophores tend to accumulate in adipose tissue due to the molecular composition similarities between the two tissues, making it challenging to generate a specific nerve signal. To alleviate this difficulty, we have synthesized a library of oxazine fluorophores based on the Nile Red scaffold, with the goal of strong adipose specificity without nerve uptake to facilitate ratiometric imaging. The library was screened for tissue specificity ex vivo and in vivo, enabling quantification of adipose-, nerve- and muscle-specific uptake as well as selection of the best candidate for adipose selectivity without nerve signal. We showed our selected Nile Red fluorophore improved nerve contrast using ratiometric imaging, especially nerve-to-adipose contrast as compared to the parent Nile Red compound or nerve-specific imaging alone. This adipose-specific Nile Red derivative could be used in future fluorescence-guided surgery applications where adipose- or nerve-specific contrast is required.
KW - Nile Red derivatives
KW - fluorescence-guided surgery
KW - nerve-specific fluorophores
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U2 - 10.1117/1.JBO.23.7.076002
DO - 10.1117/1.JBO.23.7.076002
M3 - Article
C2 - 29981230
AN - SCOPUS:85049859973
SN - 1083-3668
VL - 23
JO - Journal of Biomedical Optics
JF - Journal of Biomedical Optics
IS - 7
M1 - 076002
ER -