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Pancreas-targeted NIR fluorophores for dual-channel image-guided abdominal surgery.

Wada H, Hyun H, Vargas C, Gravier J, Park G, Gioux S, Frangioni JV, Henary M, Choi HS - Theranostics (2015)

Bottom Line: Three different 800 nm NIR fluorophores were employed for dual-channel FLARE™ imaging in pigs: 2 μmol of ZW800-1 for vessels and kidney, 1 μmol of ZW800-3C for lymph nodes, and 2 μmol of ESNF31 for adrenal glands.In pigs, T700-F produced an SBR≥2 against muscle, spleen, and lymph nodes for up to 8 h after a single intravenous injection.Pancreas-targeted NIR fluorophores combined with the FLARE dual-channel imaging system enable the real-time intraoperative pancreas imaging which helps surgeons perform safer and more curative abdominal surgeries.

View Article: PubMed Central - PubMed

Affiliation: 1. Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215. ; 2. Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.

ABSTRACT

Objective: Pancreas-related complications are some of the most serious ones in abdominal surgery. The goal of this study was to develop and validate novel near-infrared (NIR) fluorophores that would enable real-time pancreas imaging to avoid the intraoperative pancreatic injury.

Design: After initial screening of a large NIR fluorophore library, the performance of 3 selected pancreas-targeted 700 nm NIR fluorophores, T700-H, T700-F, and MB, were quantified in mice, rats, and pigs. Dose ranging using 25 and 100 nmol, and 2.5 µmol of T700-F, and its imaging kinetics over a 4 h period were tested in each species. Three different 800 nm NIR fluorophores were employed for dual-channel FLARE™ imaging in pigs: 2 μmol of ZW800-1 for vessels and kidney, 1 μmol of ZW800-3C for lymph nodes, and 2 μmol of ESNF31 for adrenal glands.

Results: T700-F demonstrated the highest signal to background ratio (SBR), with peak SBR at 4 h postinjection in mice. In pigs, T700-F produced an SBR≥2 against muscle, spleen, and lymph nodes for up to 8 h after a single intravenous injection. The combination of T700-F with each 800 nm NIR fluorophore provided simultaneous dual-channel intraoperative imaging of pancreas with surrounding organs in real time.

Conclusion: Pancreas-targeted NIR fluorophores combined with the FLARE dual-channel imaging system enable the real-time intraoperative pancreas imaging which helps surgeons perform safer and more curative abdominal surgeries.

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Related in: MedlinePlus

Chemical Structure and Optical Properties of NIR Fluorophores. Chemical structure, molecular weight (MW), and logD at pH 7.4 were depicted using MarvinSketch (ChemAxon). Absorbance (Abs) and fluorescence (FL) emission spectra were measured in 100% fetal bovine serum at pH 7.4. a) 700 nm NIR Fluorophores. b) 800 nm NIR Fluorophores.
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Figure 1: Chemical Structure and Optical Properties of NIR Fluorophores. Chemical structure, molecular weight (MW), and logD at pH 7.4 were depicted using MarvinSketch (ChemAxon). Absorbance (Abs) and fluorescence (FL) emission spectra were measured in 100% fetal bovine serum at pH 7.4. a) 700 nm NIR Fluorophores. b) 800 nm NIR Fluorophores.

Mentions: Optical properties of NIR fluorescent contrast agents. The chemical structure, absorbance, and fluorescence spectra for MB, T700-H, T700-F, ZW800-1, ZW800-3C, and ESNF31 are shown in Figure 1. Additionally, Table 1 details the optical properties of each NIR fluorophore in 100% serum. T700 fluorophores have 2-3 fold higher extinction coefficient and more than 3-fold higher QY compared to MB, which resulted in a total of 8-fold higher molecular brightness (Table 1). To summarize, MB, T700-H, and T700-F exhibited optical properties compatible with NIR fluorescence channel #1 (700 nm) of the FLARE imaging system, while ZW800-1, ZW800-3C, and ESNF31 were imaged using NIR fluorescence channel #2 (800 nm), which permits simultaneous, real-time, dual-channel intraoperative imaging.


Pancreas-targeted NIR fluorophores for dual-channel image-guided abdominal surgery.

Wada H, Hyun H, Vargas C, Gravier J, Park G, Gioux S, Frangioni JV, Henary M, Choi HS - Theranostics (2015)

Chemical Structure and Optical Properties of NIR Fluorophores. Chemical structure, molecular weight (MW), and logD at pH 7.4 were depicted using MarvinSketch (ChemAxon). Absorbance (Abs) and fluorescence (FL) emission spectra were measured in 100% fetal bovine serum at pH 7.4. a) 700 nm NIR Fluorophores. b) 800 nm NIR Fluorophores.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4265744&req=5

Figure 1: Chemical Structure and Optical Properties of NIR Fluorophores. Chemical structure, molecular weight (MW), and logD at pH 7.4 were depicted using MarvinSketch (ChemAxon). Absorbance (Abs) and fluorescence (FL) emission spectra were measured in 100% fetal bovine serum at pH 7.4. a) 700 nm NIR Fluorophores. b) 800 nm NIR Fluorophores.
Mentions: Optical properties of NIR fluorescent contrast agents. The chemical structure, absorbance, and fluorescence spectra for MB, T700-H, T700-F, ZW800-1, ZW800-3C, and ESNF31 are shown in Figure 1. Additionally, Table 1 details the optical properties of each NIR fluorophore in 100% serum. T700 fluorophores have 2-3 fold higher extinction coefficient and more than 3-fold higher QY compared to MB, which resulted in a total of 8-fold higher molecular brightness (Table 1). To summarize, MB, T700-H, and T700-F exhibited optical properties compatible with NIR fluorescence channel #1 (700 nm) of the FLARE imaging system, while ZW800-1, ZW800-3C, and ESNF31 were imaged using NIR fluorescence channel #2 (800 nm), which permits simultaneous, real-time, dual-channel intraoperative imaging.

Bottom Line: Three different 800 nm NIR fluorophores were employed for dual-channel FLARE™ imaging in pigs: 2 μmol of ZW800-1 for vessels and kidney, 1 μmol of ZW800-3C for lymph nodes, and 2 μmol of ESNF31 for adrenal glands.In pigs, T700-F produced an SBR≥2 against muscle, spleen, and lymph nodes for up to 8 h after a single intravenous injection.Pancreas-targeted NIR fluorophores combined with the FLARE dual-channel imaging system enable the real-time intraoperative pancreas imaging which helps surgeons perform safer and more curative abdominal surgeries.

View Article: PubMed Central - PubMed

Affiliation: 1. Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215. ; 2. Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.

ABSTRACT

Objective: Pancreas-related complications are some of the most serious ones in abdominal surgery. The goal of this study was to develop and validate novel near-infrared (NIR) fluorophores that would enable real-time pancreas imaging to avoid the intraoperative pancreatic injury.

Design: After initial screening of a large NIR fluorophore library, the performance of 3 selected pancreas-targeted 700 nm NIR fluorophores, T700-H, T700-F, and MB, were quantified in mice, rats, and pigs. Dose ranging using 25 and 100 nmol, and 2.5 µmol of T700-F, and its imaging kinetics over a 4 h period were tested in each species. Three different 800 nm NIR fluorophores were employed for dual-channel FLARE™ imaging in pigs: 2 μmol of ZW800-1 for vessels and kidney, 1 μmol of ZW800-3C for lymph nodes, and 2 μmol of ESNF31 for adrenal glands.

Results: T700-F demonstrated the highest signal to background ratio (SBR), with peak SBR at 4 h postinjection in mice. In pigs, T700-F produced an SBR≥2 against muscle, spleen, and lymph nodes for up to 8 h after a single intravenous injection. The combination of T700-F with each 800 nm NIR fluorophore provided simultaneous dual-channel intraoperative imaging of pancreas with surrounding organs in real time.

Conclusion: Pancreas-targeted NIR fluorophores combined with the FLARE dual-channel imaging system enable the real-time intraoperative pancreas imaging which helps surgeons perform safer and more curative abdominal surgeries.

Show MeSH
Related in: MedlinePlus