The clinical use of indocyanine green as a near‐infrared fluorescent contrast agent for image‐guided oncologic surgery

Schaafsma, Boudewijn E.; Mieog, J. Sven D.; Hutteman, Merlijn; Vorst, Joost R. van der; Kuppen, Peter J. K.; Löwik, Clemens W.G.M.; Frangioni, John V.; Velde, Cornelis J.H. van de; Vahrmeijer, Alexander L.

doi:10.1002/jso.21943

Cited by 711 publications

(626 citation statements)

References 114 publications

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“…If radiolabeled with 99m Tc, the SLN at the time of surgery would not contain a detectable amount of radioactivity. The solution to these and other scenarios is to label tilmanocept with a fluorescent reporter and perform SLN mapping with a handheld optical imaging system (18). An additional setting compatible with an optical reporter is robot-assisted surgery (19), where near-infrared-capable imaging systems are integrated into the three-dimensional viewing console (20); mapping in this setting would follow single photon emission computed tomography (SPECT) S entinel lymph node (SLN) mapping (1) of breast cancer (2,3) and melanoma (4) is well validated (5-7) and has become standard procedure in the determination of whether these cancers have metastasized to regional lymph nodes.…”

Section: Synthesis and Characterization Of Optically Labeled Tilmanoceptmentioning

confidence: 99%

A Receptor-targeted Fluorescent Radiopharmaceutical for Multireporter Sentinel Lymph Node Imaging

Emerson¹,

Limmer²,

Hall³

et al. 2012

Radiology

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Purpose:To determine the imaging and receptor-binding properties of a multireporter probe designed for sentinel lymph node (SLN) mapping via nuclear and fluorescence detection. Materials and Methods:The animal experiments were approved by the institutional animal care and use committee. A multireporter probe was synthesized by covalently attaching cyanine 7 (Cy7), a near-infrared cyanine dye, to tilmanocept, a radiopharmaceutical that binds to a receptor specific to recticuloendothelial cells. In vitro binding assays of technetium 99m ( 99m Tc) -labeled Cy7 tilmanocept were conducted at 4°C by using receptor-bearing macrophages. Optical SLN imaging after foot pad administration was performed by using two molar doses of Cy7 tilmanocept. Six mice were injected with 0.11 nmol of 99m Tc-labeled Cy7 tilmanocept (low-dose group); an additional six mice were injected with 31 nmol of 99m Tc-labeled Cy7 tilmanocept (high-dose group) to saturate the receptor sites within the SLN. After 2.5 hours of imaging, the mice were euthanized, and the sentinel and distal lymph nodes were excised and assayed for radioactivity for calculation of SLN percentage of injected dose and extraction. Four mice were used as controls for autofluorescence. Standard optical imaging software was used to plot integrated fluorescence intensity against time for calculation of the SLN uptake rate constant and scaled peak intensity. Significance was calculated by using the Student t test. Results:In vitro binding assays showed subnanomolar affinity (mean dissociation constant, 0.25 nmol/L 6 0.10 [standard deviation]). Fluorescence imaging showed a detection sensitivity of 1.6 310 3 counts ⋅ sec 21 ⋅ mW 21 per picomole of Cy7. All four imaging metrics (percentage of injected dose, SLN extraction, SLN uptake rate constant, and expected peak fluorescence intensity) exhibited higher values (P = .005 to P = .042) in the low-dose group than in the high-dose group; this finding was consistent with receptor-mediated image formation. Conclusion:The multireporter probe

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Section: Synthesis and Characterization Of Optically Labeled Tilmanoceptmentioning

confidence: 99%

A Receptor-targeted Fluorescent Radiopharmaceutical for Multireporter Sentinel Lymph Node Imaging

Emerson¹,

Limmer²,

Hall³

et al. 2012

Radiology

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“…Recently, there has been considerable focus on the potential use of indocyanine green (ICG) in intraoperative real-time imaging [10][11][12][13][14][15][16]. However, the strong binding of plasma proteins with ICG and its subsequent rapid clearance by the liver results in binding of ICG to the tumor only for a short duration after administration; thus, the use of ICG for tumor imaging applications is limited [17].…”

Section: Introductionmentioning

confidence: 99%

Intraoperative Near-infrared Fluorescence Imaging with Novel Indocyanine Green-Loaded Nanocarrier for Spinal Metastasis: A Preliminary Animal Study

Funayama¹,

Sakane²,

Abe³

et al. 2012

TOBEJ

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Abstract:Marginal resection during resection of a spinal metastasis is frequently difficult because of the presence of important tissues such as the aorta, vena cava, and dura mater, including the spinal cord adjacent to the vertebral body. Thus, there is an urgent need for novel intraoperative imaging modalities with the ability to clearly identify bone metastasis. We have proposed a novel nanocarrier loaded with indocyanine green (ICG) (ICG-lactosome) with tumor selectivity attributable to its enhanced permeation and retention (EPR) effect. We studied its feasibility in intraoperative near-infrared (NIR) fluorescence diagnosis with ICG-lactosome for imaging spinal metastasis. A rat model of subcutaneous mammary tumor and a rat model of spinal metastasis of breast cancer were used. Fluorescence emitted by the subcutaneous tumors and the spinal metastasis were clearly detected for at least 24 h. Moreover, imaging of the dissected spine revealed clear fluorescence emitted by the metastatic lesion in the L6 vertebra while the normal bone lacked fluorescence. This study was the first report on NIR fluorescence imaging of spinal metastasis in vivo. NIR fluorescence imaging with ICG-lactosome could be an effective intraoperative imaging modality for detecting spinal metastasis.

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“…8a. Recently, ICG fluorescence imaging has been attracting attention, and it is expected to be a novel tool to detect SNs [17,18]. Tajima et al [19,20] reported on intraoperative ICG fluorescence imaging using a charge-coupled device camera with a light-emitting diode (Hamamatsu Photonics, Hamamatsu, Japan).…”

Section: Resultsmentioning

confidence: 99%

Clinical significance of the anterosuperior lymph nodes along the common hepatic artery identified by sentinel node mapping in patients with gastric cancer

et al. 2015

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Background The sentinel node (SN) concept is safely applied and validated in early gastric cancer. Gastric lymph nodes are divided into five basins with the main gastric arteries, and the anterosuperior lymph nodes with the common hepatic artery (No. 8a) Methods Four hundred and twenty-nine patients with cT1N0 or cT2N0 gastric cancer underwent SN mapping. We used technetium-99 tin colloid solution and blue dye as a tracer. Results We detected SN No. 8a in 35 (8.2 %) patients. In these patients, we detected SN No. 8a with SNs that belonged to the left gastric artery (l-GA) basin (66 %), right gastroepiploic artery (r-GEA) basin (54 %), and right gastric artery (r-GA) basin (46 %). In addition, celiac artery lymph nodes were detected as SNs significantly more frequently. Function-preserving surgery was performed significantly less often in patients with SN No. 8a (p =0.018). Conclusions We found that SN No. 8a seemed to have lymphatic flow not only from the r-GA basin, but also from the l-GA basin or r-GEA basin. When SN No. 8a are detected, we should be careful to perform function-preserving surgery, even in SN-negative cases.

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The clinical use of indocyanine green as a near‐infrared fluorescent contrast agent for image‐guided oncologic surgery

Cited by 711 publications

References 114 publications

A Receptor-targeted Fluorescent Radiopharmaceutical for Multireporter Sentinel Lymph Node Imaging

A Receptor-targeted Fluorescent Radiopharmaceutical for Multireporter Sentinel Lymph Node Imaging

Intraoperative Near-infrared Fluorescence Imaging with Novel Indocyanine Green-Loaded Nanocarrier for Spinal Metastasis: A Preliminary Animal Study

Clinical significance of the anterosuperior lymph nodes along the common hepatic artery identified by sentinel node mapping in patients with gastric cancer

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