TY - JOUR
T1 - Design of a near infrared fluorescent ureter imaging agent for prevention of ureter damage during abdominal surgeries
AU - Mahalingam, Sakkarapalayam M.
AU - Putt, Karson S.
AU - Srinivasarao, Madduri
AU - Low, Philip S.
N1 - Funding Information:
Conflicts of Interest: The authors declare the following competing financial interest(s): This work was supported in part by a grant from On Target Laboratories. Philip Low is a cofounder and a member of the Board of Directors of on Target Laboratories.
Funding Information:
Funding: The authors gratefully acknowledge support from the Purdue University Center for Cancer Research, P30CA023168, the Purdue Institute for Drug Discovery, and a grant from On Target Laboratories LLC.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/6/19
Y1 - 2021/6/19
N2 - The inadvertent severing of a ureter during surgery occurs in as many as 4.5% of colorectal surgeries. To help prevent this issue, several near-infrared (NIR) dyes have been developed to assist surgeons with identifying ureter location. However, the majority of these dyes exhibit at least some issue that precludes their widespread usage such as high levels of uptake in other tissues, overlapping emission wavelengths with other NIR dyes used for other fluorescence-guided surgeries, and/or rapid excretion times through the ureters. To overcome these limitations, we have synthesized and characterized the spectral properties and biodistribution of a new series of PEGylated UreterGlow derivatives. The most promising dye, UreterGlow-11 was shown to almost exclusively excrete through the kidneys/ureters with detectable fluorescence observed for at least 12 h. Additionally, while the excitation wavelength is similar to that of other NIR dyes used for cancer resections, the emission is shifted by ~30 nm allowing for discrimination between the different fluorescence-guided surgery probes. In conclusion, these new UreterGlow dyes show promising optical and biodistribution characteristics and are good candidates for translation into the clinic.
AB - The inadvertent severing of a ureter during surgery occurs in as many as 4.5% of colorectal surgeries. To help prevent this issue, several near-infrared (NIR) dyes have been developed to assist surgeons with identifying ureter location. However, the majority of these dyes exhibit at least some issue that precludes their widespread usage such as high levels of uptake in other tissues, overlapping emission wavelengths with other NIR dyes used for other fluorescence-guided surgeries, and/or rapid excretion times through the ureters. To overcome these limitations, we have synthesized and characterized the spectral properties and biodistribution of a new series of PEGylated UreterGlow derivatives. The most promising dye, UreterGlow-11 was shown to almost exclusively excrete through the kidneys/ureters with detectable fluorescence observed for at least 12 h. Additionally, while the excitation wavelength is similar to that of other NIR dyes used for cancer resections, the emission is shifted by ~30 nm allowing for discrimination between the different fluorescence-guided surgery probes. In conclusion, these new UreterGlow dyes show promising optical and biodistribution characteristics and are good candidates for translation into the clinic.
KW - Fluorescence-guided surgery
KW - Near-infrared dye
KW - PEG pharmacokinetics
KW - Ureter imaging
KW - Spectroscopy, Near-Infrared/methods
KW - Abdomen/surgery
KW - Humans
KW - Fluorescence
KW - Tissue Distribution/physiology
KW - Optical Imaging/methods
KW - Animals
KW - Kidney/surgery
KW - Ureter/metabolism
KW - Mice
KW - Fluorescent Dyes/metabolism
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U2 - 10.3390/molecules26123739
DO - 10.3390/molecules26123739
M3 - Article
C2 - 34205289
AN - SCOPUS:85109042087
SN - 1420-3049
VL - 26
JO - Molecules
JF - Molecules
IS - 12
M1 - 3739
ER -