Dataset Information

Intraoperative Identification of Liver Cancer Microfoci Using a Targeted Near-Infrared Fluorescent Probe for Imaging-Guided Surgery.

ABSTRACT: Difficulties in the highly sensitive detection of tumour microfoci represent a critical obstacle toward improved surgical intervention in liver cancer. Conventional preoperative imaging methods and surgeons' subjective experience are limited by their inability to effectively detect tumour lesions measuring less than 2?mm; however, intraoperative fluorescence molecular imaging may overcome this limitation. Here, we synthesised an arginine-glycine-aspartic acid (RGD)-conjugated mesoporous silica nanoparticle (MSN) highly loaded with indocyanine green (ICG) dye that could accurately delineate liver cancer margins and provide excellent tumour-to-normal tissue contrast intraoperatively. The increased ICG loading capacity and tumour specificity enabled the identification of residual microtumours and satellite lesions measuring less than 1?mm in living mice. Histological analysis validated the sensitivity and accuracy of this approach. We believe this technique utilising a new fluorescent nanoprobe with intraoperative optical imaging may offer a more sensitive and accurate method for liver cancer resection guidance, resulting in better surgical outcomes.

SUBMITTER: Zeng C

PROVIDER: S-EPMC4770417 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Intraoperative Identification of Liver Cancer Microfoci Using a Targeted Near-Infrared Fluorescent Probe for Imaging-Guided Surgery.

Zeng Chaoting C Shang Wenting W Wang Kun K Chi Chongwei C Jia Xiaohua X Fang Cheng C Yang Du D Ye Jinzuo J Fang Chihua C Tian Jie J

Scientific reports 20160229

Difficulties in the highly sensitive detection of tumour microfoci represent a critical obstacle toward improved surgical intervention in liver cancer. Conventional preoperative imaging methods and surgeons' subjective experience are limited by their inability to effectively detect tumour lesions measuring less than 2 mm; however, intraoperative fluorescence molecular imaging may overcome this limitation. Here, we synthesised an arginine-glycine-aspartic acid (RGD)-conjugated mesoporous silica n ...[more]

PMID: 26923919

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Project description:BACKGROUND:To meet clinical needs, fluorescence-guided surgery has emerged as a new technique that guides surgeons in the resection of cancerous tissue by highlighting tumour lesions during surgery. We aimed to evaluate the novel ovarian cancer-specific antibody fluorescent probe COC183B2-800 (COC183B2 conjugated with IRDye800CW) in tumour-specific imaging to determine if it can help surgeons remove malignant lesions under fluorescence guidance. METHODS:The expression of OC183B2 antigen in epithelial ovarian cancer (EOC) tissues and cell lines was determined using immunohistochemistry (IHC). Western blotting was used to verify the expression of OC183B2 in SKOV3-Luc tumours. Antibodies against OC183B2 and mouse immunoglobulin G1 (IgG1) were conjugated with IRDye800CW to develop the antibody fluorescent probes COC183B2-800 and IgG-800 (immunoglobulin G1 conjugated with IRDye800CW). A subcutaneous mouse tumour model of SKOV3-Luc cells was constructed. Bioluminescent imaging (BLI) was conducted to detect the tumour location. Near-infrared fluorescence (NIRF) imaging was performed after the mice were injected with imaging agents. The mice were sacrificed 96?h postinjection, and the biodistribution assays were performed using NIRF imaging. RESULTS:In 69 EOC patients, the total positive rate of OC183B2 in EOC tissues was 89.9% (62/69). Expression of the OC183B2 antigen was positive in SKOV3-Luc, 3AO, ES2 and A2780 cells. The OC183B2 antigen could be detected in SKOV3-Luc tumours. NIRF imaging of the COC183B2-800 probe at different doses showed a high fluorescent signal at the tumour location that was in line with the site detected by bioluminescent imaging. The tumour background ratio (TBR) was significantly higher in the COC183B2-800 group than in the IgG-800, IRDye800CW and PBS groups. The fluorescent probe COC183B2-800 is metabolized mainly through the liver and does not accumulate in other organs. CONCLUSIONS:COC183B2-800 shows effective tumour-specific targeting of EOC and is a promising diagnostic and therapeutic tool for fluorescence-guided surgery.

Project description:BACKGROUND:Although real-time localization of gliomas has improved with intraoperative image guidance systems, these tools are limited by brain shift, surgical cavity deformation, and expense. OBJECTIVE:To propose a novel method to perform near-infrared (NIR) imaging during glioma resections based on preclinical and clinical investigations, in order to localize tumors and to potentially identify residual disease. METHODS:Fifteen patients were identified and administered a Food and Drug Administration-approved, NIR contrast agent (Second Window indocyanine green [ICG], 5 mg/kg) before surgical resection. An NIR camera was utilized to localize the tumor before resection and to visualize surgical margins following resection. Neuropathology and magnetic resonance imaging data were used to assess the accuracy and precision of NIR fluorescence in identifying tumor tissue. RESULTS:NIR visualization of 15 gliomas (10 glioblastoma multiforme, 1 anaplastic astrocytoma, 2 low-grade astrocytoma, 1 juvenile pilocytic astrocytoma, and 1 ganglioglioma) was performed 22.7 hours (mean) after intravenous injection of ICG. During surgery, 12 of 15 tumors were visualized with the NIR camera. The mean signal-to-background ratio was 9.5 ± 0.8 and fluorescence was noted through the dura to a maximum parenchymal depth of 13 mm. The best predictor of positive fluorescence was enhancement on T1-weighted imaging; this correlated with signal-to-background ratio (P = .03). Nonenhancing tumors did not demonstrate NIR fluorescence. Using pathology as the gold standard, the technique demonstrated a sensitivity of 98% and specificity of 45% to identify tumor in gadolinium-enhancing specimens (n = 71). CONCLUSION:With the use of Second Window ICG, gadolinium-enhancing tumors can be localized through brain parenchyma intraoperatively. Its utility for margin detection is promising but limited by lower specificity. ABBREVIATIONS:5-ALA, 5-aminolevulinic acidEPR, enhanced permeability and retentionFDA, Food and Drug AdministrationGBM, glioblastomaICG, indocyanine greenNIR, near-infraredNPV, negative predictive valuePPV, positive predictive valueROC, receiver operating characteristicROI, region of interestSBR, signal-to-background ratioWHO, World Health Organization.

Dataset Information

Intraoperative Identification of Liver Cancer Microfoci Using a Targeted Near-Infrared Fluorescent Probe for Imaging-Guided Surgery.

Publications

Intraoperative Identification of Liver Cancer Microfoci Using a Targeted Near-Infrared Fluorescent Probe for Imaging-Guided Surgery.

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