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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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Intraoperative Pancreas Imaging in SD Rats: a) 1.2 µmol of MB and 100 nmol of T700-F were injected intravenously 15 min and 4 h prior to imaging, respectively (n = 3). Abbreviations used are: Bl, bladder; Du, duodenum; In, intestine; Ki, kidney; Li, liver; Pa, pancreas; Sp, spleen. Arrows indicate pancreas and arrowheads indicate autofluorescence of food in lumen of intestine. Scale bars = 1 cm. All NIR fluorescence images have identical exposure times and normalizations. b) Histological analysis: Consecutive sections from rat pancreas stained with H&E or unstained were observed using an NIR fluorescence microscope. Abbreviations used are: Ac, acinus; IL, islets of Langerhans; PD, pancreatic duct. Scale bars = 300 µm. All NIR fluorescence images for each condition have identical exposure times and normalizations.
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Figure 3: Intraoperative Pancreas Imaging in SD Rats: a) 1.2 µmol of MB and 100 nmol of T700-F were injected intravenously 15 min and 4 h prior to imaging, respectively (n = 3). Abbreviations used are: Bl, bladder; Du, duodenum; In, intestine; Ki, kidney; Li, liver; Pa, pancreas; Sp, spleen. Arrows indicate pancreas and arrowheads indicate autofluorescence of food in lumen of intestine. Scale bars = 1 cm. All NIR fluorescence images have identical exposure times and normalizations. b) Histological analysis: Consecutive sections from rat pancreas stained with H&E or unstained were observed using an NIR fluorescence microscope. Abbreviations used are: Ac, acinus; IL, islets of Langerhans; PD, pancreatic duct. Scale bars = 300 µm. All NIR fluorescence images for each condition have identical exposure times and normalizations.

Mentions: Intraoperative pancreas imaging and histology in rats. We compared T700-F with MB in SD rats by injecting 100 nmol of T700-F and 1.2 µmol (1.5 mg/kg) of MB, respectively (Figure 3A). Although MB highlighted the pancreas immediately after a single intravenous injection, the fluorescent signal in pancreas diminished rapidly after 15 min. Conversely, T700-F showed strong pancreas signal and low background uptake even at 4 h post-injection. After intraoperative imaging, we resected the pancreas and performed histological analysis (Figure 3B). NIR fluorescence microscopy confirmed 700 nm fluorescence signal in the resected pancreatic tissues. Both fluorophores accumulated in the intracellular space: T700-F stained both the exocrine pancreas (acini; AC) cells and islets of Langerhans (IL), while MB exhibited proportionally higher islet uptake.


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)

Intraoperative Pancreas Imaging in SD Rats: a) 1.2 µmol of MB and 100 nmol of T700-F were injected intravenously 15 min and 4 h prior to imaging, respectively (n = 3). Abbreviations used are: Bl, bladder; Du, duodenum; In, intestine; Ki, kidney; Li, liver; Pa, pancreas; Sp, spleen. Arrows indicate pancreas and arrowheads indicate autofluorescence of food in lumen of intestine. Scale bars = 1 cm. All NIR fluorescence images have identical exposure times and normalizations. b) Histological analysis: Consecutive sections from rat pancreas stained with H&E or unstained were observed using an NIR fluorescence microscope. Abbreviations used are: Ac, acinus; IL, islets of Langerhans; PD, pancreatic duct. Scale bars = 300 µm. All NIR fluorescence images for each condition have identical exposure times and normalizations.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4265744&req=5

Figure 3: Intraoperative Pancreas Imaging in SD Rats: a) 1.2 µmol of MB and 100 nmol of T700-F were injected intravenously 15 min and 4 h prior to imaging, respectively (n = 3). Abbreviations used are: Bl, bladder; Du, duodenum; In, intestine; Ki, kidney; Li, liver; Pa, pancreas; Sp, spleen. Arrows indicate pancreas and arrowheads indicate autofluorescence of food in lumen of intestine. Scale bars = 1 cm. All NIR fluorescence images have identical exposure times and normalizations. b) Histological analysis: Consecutive sections from rat pancreas stained with H&E or unstained were observed using an NIR fluorescence microscope. Abbreviations used are: Ac, acinus; IL, islets of Langerhans; PD, pancreatic duct. Scale bars = 300 µm. All NIR fluorescence images for each condition have identical exposure times and normalizations.
Mentions: Intraoperative pancreas imaging and histology in rats. We compared T700-F with MB in SD rats by injecting 100 nmol of T700-F and 1.2 µmol (1.5 mg/kg) of MB, respectively (Figure 3A). Although MB highlighted the pancreas immediately after a single intravenous injection, the fluorescent signal in pancreas diminished rapidly after 15 min. Conversely, T700-F showed strong pancreas signal and low background uptake even at 4 h post-injection. After intraoperative imaging, we resected the pancreas and performed histological analysis (Figure 3B). NIR fluorescence microscopy confirmed 700 nm fluorescence signal in the resected pancreatic tissues. Both fluorophores accumulated in the intracellular space: T700-F stained both the exocrine pancreas (acini; AC) cells and islets of Langerhans (IL), while MB exhibited proportionally higher islet uptake.

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