Jaepyeong Cha, PhD1, Jung-Man Namgoong, MD1, Kihoon Kim, MD, PhD1, Aline Broch, MD1, Roger Nani, PhD2, Venu Bandi, PhD2, Martin J Schnermann, PhD2, Peter Kim, MD, PhD1. 1Children’s National Health System, 2NIH/NCI
Introduction: Accurate, real-time visualization is critical for efficient, effective and safe surgery. Although optical imaging using near-infrared (NIR) fluorescence has been used for visualization of anatomic structures and physiologic functions in open and minimally invasive surgeries, its efficacy and adoption remain suboptimal due to the lack of specificity and sensitivity. Herein, we report a novel class of compounds, which are exclusively metabolized in liver or kidney, rapidly excreted into to biliary or urinary systems, and emitted two different NIR fluorescence spectrums.
Methods: Novel, water-soluble heptamethine cyanines; Compound X (biliary) and Compound Y (urinary), unreactive towards gluthathione and the cellular proteome were synthesized, and visualized using real-time, dual-color NIR imaging device. Sprague-dawley rats (n = 12) and Yorkshire pigs (n = 9) were used to demonstrate and validate its usefulness, distributed into a control group (ICG; rat n=3, IRDye800CW rat n=3), a biliary group (Compound X; rat n=3, pig n=3), a urinary group (Compound Y; rat n=3, pig n=3), and dual-labeling group (Compound X&Y; rat n=3, pig n=3). Each rat and pig received one or two of the compounds at optimized dose of 0.09-mg/kg intravenously, fluorescence signals and bio-distributions were monitored and recorded over time. The target to background ratio (TBR) was calculated in each target systems and compared to assess sensitivity and specificity.
Results: Compound X was rapidly cleared from liver within 15 minutes after intravenous injection while the fluorescence signals in biliary system lasted up to 1 hour both in rats and pigs. Compound Y showed significant renal excretion up to 4 hours and the urinary signals remained up to 2 hours. They were both highly specific to target organs with TBR values of 4.23 (biliary), 6.32 (urinary) and 1.23 (cf. ICG) at peak signals. These new compounds have approximately 2-3 times higher quantum yields than ICG and 1.75 to 2.5 times higher specificity to kidney and liver than IRDye800CW. One-way ANOVA showed significant differences between control, biliary, and urinary group (p<0.0001.) Dual-labeling results also showed a complete separation of these two metabolic systems (p=0.008) and a real-time display of these two systems were clearly visualized with pseudo-colored labeling inside the animal body.
Conclusion: We report a new generation of organ-specific, real-time fluorescent markers for intraoperative visualization, navigation and potential geo-fencing. These new compounds have significantly higher quantum yields and higher specificity to visualize kidney and/or liver than any currently available reagents.
Presented at the SAGES 2017 Annual Meeting in Houston, TX.
Abstract ID: 86518
Program Number: P497
Presentation Session: iPoster Session (Non CME)
Presentation Type: Poster
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