Extracellular vesicles-based pre-targeting strategy enables multi-modal imaging of orthotopic colon cancer and image-guided surgery

Abstract Backgroud Colon cancer contributes to high mortality rates as the result of incomplete resection in tumor surgery. Multimodal imaging can provide preoperative evaluation and intraoperative image-guiding. As biocompatible nanocarriers, extracellular vesicles hold great promise for multimodal imaging. In this study, we aim to synthesized an extracellular vesicles-based nanoprobe to visualize colon cancer with positron-emission tomography/computed tomography (PET/CT) and near-infrared fluorescence (NIRF) imaging, and investigated its utility in image-guided surgery of colon cancer in animal models. Results Extracellular vesicles were successfully isolated from adipose-derived stem cells (ADSCs), and their membrane vesicles were observed under TEM. DLS detected that the hydrodynamic diameters of the extracellular vesicles were approximately 140 nm and the zeta potential was − 7.93 ± 0.24 mV. Confocal microscopy showed that extracellular vesicles had a strong binding ability to tumor cells. A click chemistry-based pre-targeting strategy was used to achieve PET imaging in vivo. PET images and the biodistribution results showed that the best pre-targeting time was 20 h, and the best imaging time was 2 h after the injection of 68 Ga-L-NETA-DBCO. The NIRF images showed that the tumor had clear images at all time points after administration of nanoparticles and the Tumor/Muscle ratio peaked at 20 h after injection. Our data also showed that both PET/CT and NIRF imaging clearly visualized the orthotopic colon cancer models, providing preoperative evaluation. Under real-time NIRF imaging, the tumor location and tumor boundary could be clearly observed. Conclusions In brief, this novel nanoprobe may be useful for multi-modal imaging of colon cancer and NIRF image-guided surgery. More importantly, this study provides a new possibility for clinical application of extracellular vesicles as nanocarriers. Graphic Abstract

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Extracellular Vesicles-based Pre-Targeting Strategy Enables Multi-Modal Imaging of Orthotopic Colon Cancer and Image-Guided Surgery

10.21203/rs.3.rs-324394/v1 ◽

2021 ◽

Author(s):

Rui An ◽

Boping Jing ◽

Ruijie Qian ◽

Dawei Jiang ◽

Yongkang Gai ◽

...

Keyword(s):

Colon Cancer ◽

Extracellular Vesicles ◽

Multimodal Imaging ◽

Preoperative Evaluation ◽

Image Guided Surgery ◽

Guided Surgery ◽

Image Guided ◽

Nirf Imaging ◽

Pet Ct ◽

Targeting Strategy

Abstract BackgroudColon cancer contributes to high mortality rates as the result of incomplete resection in tumor surgery. Multimodal imaging can provide preoperative evaluation and intraoperative image-guiding. As biocompatible nanocarriers, extracellular vesicles hold great promise for multimodal imaging. In this study, we aim to synthesized an extracellular vesicles-based nanoprobe to visualize colon cancer with positron-emission tomography/computed tomography (PET/CT) and near-infrared fluorescence (NIRF) imaging, and investigated its utility in image-guided surgery of colon cancer in animal models. ResultsExtracellular vesicles were successfully isolated from adipose-derived stem cells (ADSCs), and their membrane vesicles were observed under TEM. DLS detected that the hydrodynamic diameters of the extracellular vesicles were approximately 140 nm and the zeta potential was −7.93 ± 0.24 mV. Confocal microscopy showed that extracellular vesicles had a strong binding ability to tumor cells. A click chemistry-based pre-targeting strategy was used to achieve PET imaging in vivo. PET images and the biodistribution results showed that the best pre-targeting time was 20 h, and the best imaging time was 2 h after the injection of 68Ga-L-NETA-DBCO. The NIRF images showed that the tumor had clear images at all time points after administration of nanoparticles and the Tumor/Muscle ratio peaked at 20 h after injection. Our data also showed that both PET/CT and NIRF imaging clearly visualized the orthotopic colon cancer models, providing preoperative evaluation. Under real-time NIRF imaging, the tumor location and tumor boundary could be clearly observed. ConclusionsIn brief, this novel nanoprobe may be useful for multi-modal imaging of colon cancer and NIRF image-guided surgery. More importantly, this study provides a new possibility for clinical application of extracellular vesicles as nanocarriers.

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Hyperspectral imaging for colon cancer classification in surgical specimens: towards optical biopsy during image-guided surgery

2020 42nd Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC) ◽

10.1109/embc44109.2020.9176543 ◽

2020 ◽

Author(s):

Francesca Manni ◽

Roger Fonolla ◽

Fons van der Sommen ◽

Svetlana Zinger ◽

Caifeng Shan ◽

...

Keyword(s):

Colon Cancer ◽

Hyperspectral Imaging ◽

Cancer Classification ◽

Optical Biopsy ◽

Image Guided Surgery ◽

Guided Surgery ◽

Image Guided

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Comparison of histopathology and preoperative 18F-FDG-PET/CT of osteomyelitis aiming for image guided surgery: A preliminary trial

Injury ◽

10.1016/j.injury.2020.02.062 ◽

2020 ◽

Vol 51 (4) ◽

pp. 871-877

Author(s):

Motoyuki Takaki ◽

Nobuyuki Takenaka ◽

Keisuke Mori ◽

Shota Harada ◽

Tomohiko Asahara ◽

...

Keyword(s):

Fdg Pet ◽

Image Guided Surgery ◽

Preliminary Trial ◽

Guided Surgery ◽

Image Guided ◽

Pet Ct ◽

18F Fdg ◽

Fdg Pet Ct

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Radioimmunoguided surgery (RIGS), PET/CT image-guided surgery, and fluorescence image-guided surgery: Past, present, and future

Journal of Surgical Oncology ◽

10.1002/jso.20869 ◽

2007 ◽

Vol 96 (4) ◽

pp. 297-308 ◽

Cited By ~ 27

Author(s):

Duxin Sun ◽

Mark Bloomston ◽

George Hinkle ◽

Osama Habib Al-Saif ◽

Nathan C. Hall ◽

...

Keyword(s):

Image Guided Surgery ◽

Ct Image ◽

Radioimmunoguided Surgery ◽

Fluorescence Image ◽

Guided Surgery ◽

Image Guided ◽

Pet Ct

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Multimodal imaging platform for image-guided surgery: application to blood perfusion assessment

Multimodal Biomedical Imaging XVI ◽

10.1117/12.2578461 ◽

2021 ◽

Author(s):

Silvère Ségaud ◽

Enagnon Aguénounon ◽

Joseph Angelo ◽

Sara Gravelyn ◽

Henrique Waxin ◽

...

Keyword(s):

Multimodal Imaging ◽

Blood Perfusion ◽

Image Guided Surgery ◽

Guided Surgery ◽

Image Guided ◽

Perfusion Assessment

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Differentiation of healthy and malignant tissue in colon cancer patients using optical spectroscopy: A tool for image-guided surgery

Lasers in Surgery and Medicine ◽

10.1002/lsm.22388 ◽

2015 ◽

Vol 47 (7) ◽

pp. 559-565 ◽

Cited By ~ 12

Author(s):

G.C. Langhout ◽

J.W. Spliethoff ◽

S.J. Schmitz ◽

A.G.J. Aalbers ◽

M.-L.F. van Velthuysen ◽

...

Keyword(s):

Colon Cancer ◽

Cancer Patients ◽

Optical Spectroscopy ◽

Image Guided Surgery ◽

Malignant Tissue ◽

Guided Surgery ◽

Image Guided

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Three-Dimensional Localization: From Image-Guided Surgery to Information-Guided Therapy

Methods ◽

10.1006/meth.2001.1234 ◽

2001 ◽

Vol 25 (2) ◽

pp. 186-200 ◽

Cited By ~ 20

Author(s):

Richard D. Bucholz ◽

Kurt R. Smith ◽

Keith A. Laycock ◽

Leslie L. McDurmont

Keyword(s):

Three Dimensional ◽

Image Guided Surgery ◽

Guided Surgery ◽

Image Guided ◽

Guided Therapy

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Radiopharmaceutical and Eu3+ doped gadolinium oxide nanoparticles mediated triple-excited fluorescence imaging and image-guided surgery

Journal of Nanobiotechnology ◽

10.1186/s12951-021-00920-6 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Xiaojing Shi ◽

Caiguang Cao ◽

Zeyu Zhang ◽

Jie Tian ◽

Zhenhua Hu

Keyword(s):

Fluorescent Probes ◽

Signal Intensity ◽

Tumor Imaging ◽

Tumor Resection ◽

Optical Signal ◽

Gadolinium Oxide ◽

Image Guided Surgery ◽

Guided Surgery ◽

Image Guided ◽

The Impact

AbstractCerenkov luminescence imaging (CLI) is a novel optical imaging technique that has been applied in clinic using various radionuclides and radiopharmaceuticals. However, clinical application of CLI has been limited by weak optical signal and restricted tissue penetration depth. Various fluorescent probes have been combined with radiopharmaceuticals for improved imaging performances. However, as most of these probes only interact with Cerenkov luminescence (CL), the low photon fluence of CL greatly restricted it’s interaction with fluorescent probes for in vivo imaging. Therefore, it is important to develop probes that can effectively convert energy beyond CL such as β and γ to the low energy optical signals. In this study, a Eu3+ doped gadolinium oxide (Gd2O3:Eu) was synthesized and combined with radiopharmaceuticals to achieve a red-shifted optical spectrum with less tissue scattering and enhanced optical signal intensity in this study. The interaction between Gd2O3:Eu and radiopharmaceutical were investigated using 18F-fluorodeoxyglucose (18F-FDG). The ex vivo optical signal intensity of the mixture of Gd2O3:Eu and 18F-FDG reached 369 times as high as that of CLI using 18F-FDG alone. To achieve improved biocompatibility, the Gd2O3:Eu nanoparticles were then modified with polyvinyl alcohol (PVA), and the resulted nanoprobe PVA modified Gd2O3:Eu (Gd2O3:Eu@PVA) was applied in intraoperative tumor imaging. Compared with 18F-FDG alone, intraoperative administration of Gd2O3:Eu@PVA and 18F-FDG combination achieved a much higher tumor-to-normal tissue ratio (TNR, 10.24 ± 2.24 vs. 1.87 ± 0.73, P = 0.0030). The use of Gd2O3:Eu@PVA and 18F-FDG also assisted intraoperative detection of tumors that were omitted by preoperative positron emission tomography (PET) imaging. Further experiment of image-guided surgery demonstrated feasibility of image-guided tumor resection using Gd2O3:Eu@PVA and 18F-FDG. In summary, Gd2O3:Eu can achieve significantly optimized imaging property when combined with 18F-FDG in intraoperative tumor imaging and image-guided tumor resection surgery. It is expected that the development of the Gd2O3:Eu nanoparticle will promote investigation and application of novel nanoparticles that can interact with radiopharmaceuticals for improved imaging properties. This work highlighted the impact of the nanoprobe that can be excited by radiopharmaceuticals emitting CL, β, and γ radiation for precisely imaging of tumor and intraoperatively guide tumor resection.

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