A multimodal nano agent for image-guided cancer surgery (original) (raw)
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Journal of Nanobiotechnology
Surgical resection is the cornerstone of solid tumour treatment. Current techniques for evaluating margin statuses, such as frozen section, imprint cytology, and intraoperative ultrasound, are helpful. However, an intraoperative assessment of tumour margins that is accurate and safe is clinically necessary. Positive surgical margins (PSM) have a well-documented negative effect on treatment outcomes and survival. As a result, surgical tumour imaging methods are now a practical method for reducing PSM rates and improving the efficiency of debulking surgery. Because of their unique characteristics, nanoparticles can function as contrast agents in image-guided surgery. While most image-guided surgical applications utilizing nanotechnology are now in the preclinical stage, some are beginning to reach the clinical phase. Here, we list the various imaging techniques used in image-guided surgery, such as optical imaging, ultrasound, computed tomography, magnetic resonance imaging, nuclear m...
Theranostics, 2014
Cancer is a major threat to human health. Diagnosis and treatment using precision medicine is expected to be an effective method for preventing the initiation and progression of cancer. Although anatomical and functional imaging techniques such as radiography, computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) have played an important role for accurate preoperative diagnostics, for the most part these techniques cannot be applied intraoperatively. Optical molecular imaging is a promising technique that provides a high degree of sensitivity and specificity in tumor margin detection. Furthermore, existing clinical applications have proven that optical molecular imaging is a powerful intraoperative tool for guiding surgeons performing precision procedures, thus enabling radical resection and improved survival rates. However, detection depth limitation exists in optical molecular imaging methods and further breakthroughs from optical to mul...
Receptor-Targeted Fluorescence-Guided Surgery With Low Molecular Weight Agents
Frontiers in Oncology, 2021
Cancer surgery remains the primary treatment option for most solid tumors and can be curative if all malignant cells are removed. Surgeons have historically relied on visual and tactile cues to maximize tumor resection, but clinical data suggest that relapse occurs partially due to incomplete cancer removal. As a result, the introduction of technologies that enhance the ability to visualize tumors in the operating room represents a pressing need. Such technologies have the potential to revolutionize the surgical standard-of-care by enabling real-time detection of surgical margins, subclinical residual disease, lymph node metastases and synchronous/metachronous tumors. Fluorescence-guided surgery (FGS) in the near-infrared (NIRF) spectrum has shown tremendous promise as an intraoperative imaging modality. An increasing number of clinical studies have demonstrated that tumor-selective FGS agents can improve the predictive value of fluorescence over non-targeted dyes. Whereas NIRF-labe...
Fluorescence molecular imaging systems for intraoperative image-guided surgery
Applied Spectroscopy Reviews, 2017
Despite advances in diagnostic and therapeutic technology of human diseases, cancer remains among the leading causes of morbidity and mortality worldwide. The development of molecular imaging has made it possible to diagnose and treat cancer at early stages, which increases the likelihood of survival. Nuclear medicine has played a key role in diagnosis and staging of human malignancy. However, most imaging technology can only be used in the preoperative diagnosis stage, and these methods are time consuming and often expose patients to a high amount of radiation. Combined with appropriate contrast agents, fluorescence molecular imaging is an easy-to-use imaging tool that can be
2020
Background: The goal of fluorescence guided surgery (FGS) in oncology is to improve the surgical therapeutic index by enhancing contrast between cancerous and healthy tissue. However, optimal discrimination between these tissues is complicated by the non-specific uptake and retention of molecular targeted agents and the heterogeneity of fluorescence signal. Paired-agent imaging (PAI) employs co-administration of an untargeted imaging agent with a molecular targeted agent, providing a normalization factor to minimize nonspecific and heterogeneous signals. The resulting measured binding potential is quantitative and equivalent to in vivo immunohistochemistry of the target protein. This study demonstrates that PAI improves the accuracy of tumor-to-healthy tissue discrimination compared to single agent imaging for in vivo FGS. Methods: PAI using a fluorescent anti-EGFR affibody molecule (ABY-029, eIND 122681) with untargeted IRDye 700DX carboxylate was compared to ABY-029 alone in an or...
New technologies for fluorescence image-guided surgery
2014
To date, surgery is the most common and successful way to treat cancer. Tumour identification during surgery, however, can be challenging as it relies on the surgeon’s ability to differentiate healthy from diseased tissue, based on visual appearance and palpation. Additional contrast mechanisms are needed to further improve cancer detection during surgery. In this work, I explore the possibility of improving surgical outcomes by using intra-operative fluorescence imaging technologies to identify otherwise invisible lesions. A theoretical model is developed to quantify and characterise the imaging performance of fluorescence image-guided surgery (FIGS) and to guide the development of imaging systems. This model shows excellent potential for performance characterisation of FIGS devices, particularly when small lesions are involved. The design, development and testing of FIGS devices for open and keyhole surgery are described. These devices exploit near infrared (NIR) wavelengths to ac...
Cancer control : journal of the Moffitt Cancer Center
The excision of tumors by wide local excision is challenging because the mass must be removed entirely without ever viewing it directly. Positive margin rates in sarcoma resection remain in the range of 20% to 35% and are associated with increased recurrence and decreased survival. Fluorescence-guided surgery (FGS) may improve surgical accuracy and has been utilized in other surgical specialties. ABY-029, an anti-epidermal growth factor receptor Affibody molecule covalently bound to the near-infrared fluorophore IRDye 800CW, is an excellent candidate for future FGS applications in sarcoma resection; however, conventional methods with direct surface tumor visualization are not immediately applicable. A novel technique involving imaging through a margin of normal tissue is needed. We review the past and present applications of FGS and present a novel concept of indirect FGS for visualizing tumor through a margin of normal tissue and aiding in excising the entire lesion as a single, co...
EpCAM as multi-tumour target for near-infrared fluorescence guided surgery
BMC cancer, 2016
Evaluation of resection margins during cancer surgery can be challenging, often resulting in incomplete tumour removal. Fluorescence-guided surgery (FGS) aims to aid the surgeon to visualize tumours and resection margins during surgery. FGS relies on a clinically applicable imaging system in combination with a specific tumour-targeting contrast agent. In this study EpCAM (epithelial cell adhesion molecule) is evaluated as target for FGS in combination with the novel Artemis imaging system. The NIR fluorophore IRDye800CW was conjugated to the well-established EpCAM specific monoclonal antibody 323/A3 and an isotype IgG1 as control. The anti-EpCAM/800CW conjugate was stable in serum and showed preserved binding capacity as evaluated on EpCAM positive and negative cell lines, using flow cytometry and cell-based plate assays. Four clinically relevant orthotopic tumour models, i.e. colorectal cancer, breast cancer, head and neck cancer, and peritonitis carcinomatosa, were used to evaluat...
Real-Time Fluorescence Image-Guided Oncologic Surgery
Advances in Cancer Research, 2014
Medical imaging plays a critical role in cancer diagnosis and planning. Many of these patients rely on surgical intervention for curative outcomes. This requires a careful identification of the primary and microscopic tumors, and the complete removal of cancer. Although there have been efforts to adapt traditional-imaging modalities for intraoperative image guidance, they suffer from several constraints such as large hardware footprint, high-operation cost, and disruption of the surgical workflow. Because of the ease of image acquisition, relatively low-cost devices and intuitive operation, optical imaging methods have received tremendous interests for use in real-time image-guided surgery. To improve imaging depth under low interference by tissue autofluorescence, many of these applications utilize light in the near-infrared (NIR) wavelengths, which is invisible to human eyes. With the availability of a wide selection of tumor-avid contrast agents, advancements in imaging sensors, electronic and optical designs, surgeons are able to combine different attributes of NIR optical imaging techniques to improve treatment outcomes. The emergence of diverse commercial and experimental image guidance systems, which are in various stages of clinical translation, attests to the potential high impact of intraoperative optical imaging methods to improve speed of oncologic surgery with high accuracy and minimal margin positivity.
Optical image-guided surgery—where do we stand?
2011
In cancer surgery, intra-operative assessment of the tumor-free margin, which is critical for the prognosis of the patient, relies on the visual appearance and palpation of the tumor. Optical imaging techniques provide real-time visualization of the tumor, warranting intra-operative image-guided surgery. Within this field, imaging in the near-infrared light spectrum offers two essential advantages: increased tissue penetration of light and an increased signal-tobackground-ratio of contrast agents. In this article, we review the various techniques, contrast agents, and camera systems that are currently used for image-guided surgery. Furthermore, we provide an overview of the wide range of molecular contrast agents targeting specific hallmarks of cancer and we describe perspectives on its future use in cancer surgery.