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Currently, surgeons rely mainly on visual (normal white light) and haptic feedback during surgeryImaging methods such as X-rays, PET/CT, or MRI are primarily used for preoperative diagnosis, surgical planning, or mid-term evaluation, but they are difficult to integrate into operating room scenariosDuring surgery, it is possible to damage the surrounding tissue due to excessive excision or to affect the patient's prognosis due to incomplete resectionfluorescence-guided surgery
so it is important to judge the tumor boundaryIn order to crack the technical bottleneck and achieve more precise tumor removal, an intraoperative navigation technique called fluorescence guided surgery (FGS) has gradually become the "favorite" of surgeonsThe technique uses a specific wavelength to stimulate light exposure, which stimulates the tumor's own fluorescence, stranded fluorescent molecules or cell-intake of the external fluorescent substance to emit fluorescence, leading the artist to accurately remove the tumorfluorescence-guided surgery uses near-infrared fluorescence (NIR, 700-900nm), such as ICG, Cy5, and IRDye800CWCompared with visible light, NIR fluorescent tissue penetration (5-10mm), small scattering, low background fluorescence, more suitable for clinical in-body imagingAt present, as the only nIR fluorescence approved for clinical use, indigo green (ICG) has begun to bear fruit in applications such as liver cancer development and outpost lymph node developmentBut since ICG itself is not tumor-targeted, since then, the targeted fluorescent molecular probe has begun to enter people's field of visionthe principle of fluorescent molecular probe imaging in the techniquefigure above: a diagram of the potential application of targeted fluorescent molecular probesthe following image: Fluorescence guidance in open and laparoscopic surgeryIntravenous tracer (within 1 hour before surgery, depending on the tracer), tumors or other target tissues using a professional near-infrared camera to guide the surgeon in real-time removalImmediately after removal, the specimen can be imaged with a fluorescent camera and microscope on the back table (the table used for analysis) in the operating roomAs a result, pathologists can quickly examine fluorescence on the removal edges and provide quick feedback to the surgeon targeted fluorescent molecular probe
probe design
targeted fluorescent probe is usually composed of three parts: identification group (recognition element), reporting group (fluorophore) and connecting body (linker) The identification of the group determines the choice and specificity of the probe, the reporting group determines its sensitivity, and the connecting body adjusts the characteristics of the probe size, pharmacokinetics, biological distribution, and live conditions identification groups are the core part of the probe, and there are two main identification strategies: one is to use receptors that are overexpressed on the surface of cancer cells, such as folic acid receptors and EGFR, and the other is to use enzymes that are overexpressed in tumor tissue, such as tissue proteases (cathepesins) and matrix metalloproteinases (MMPs), which are often associated with tumor diffusion and metastase target fluorescence probe design strategy A: Probe structure B: probe C: enzyme-activated probe probe application fluorescent molecular imaging with molecular probe and fluorescent endoscopy device, the invisible tumor "precise lighting" for wideuse in surgical navigation and early diagnosis surgical navigation
surgical residues and poor prognosis and cancer recurrence are associated, and excessive removal may harm the surrounding normal tissue Therefore, it is very important to judge the tumor boundary Target fluorescent probes can light up cancer cells in real time during surgery, helping doctors determine tumor boundaries and discover metastatic lesions, a concept that is referred to above early diagnosis in China, the incidence and mortality rate of malignant tumors in the digestive tract is much higher than the world average Early digestive tract cancer is not really scary, the prognosis is good, and the survival rate is as high as 90% for 5 years after treatment Endoscopy is the main tool for early cancer diagnosis of the digestive tract, but the existing endoscopic examination technology can not meet the clinical needs of gastrointestinal cancer diagnosis, the early cancer diagnosis rate is less than 20% The main problems existing endoscopy include: endoscopic biopsies rely on the experience of doctors, are prone to early micro-lesions, and white light examination depth is limited and can only detect surface lesions targeted fluorescent probecancans can specifically light diseased cells, helping doctors to detect susceptible lesions and improving the detection rate of early cancer EMI-137 probe can improve the detection rate of colorectal lesions
the status quo of clinical research on the probe
Current, the research of targeted fluorescent molecular probe is significantly ahead of the domestic, including BLZ-100, OTL38, EMI-137 and Beva mono-anti-IRDye800CW and other targeted fluorescent probes have entered clinical research, in which OTL38 clinical trials for ovarian cancer have entered phase III, in addition to a series of clinical research is being developed on Jingguan Medical in China, Suzhou Jingguan Medical is currently the only company to provide customers with targeted fluorescent molecular probe customization services, probe verification services, probe production and clinical transformation services and other overall solutions In just one year, Jingguan Medical has developed nearly ten fluorescent molecular probes for customers and assisted them in developing innovative diagnostic and therapeutic technologies Jingguan aims to "precisely light up tumors" and is committed to being the promoter of fluorescent molecular imagery probe design synthesis and optimization design: screening tumor-specific target groups to accurately mark your target with near-infrared fluorescent dyes synthesis and optimization: the overall optimization of the probe through computer-aided design, amber suppression, and location coupling, and the improvement of pharmacokinetic properties probe verification probe production effective operating procedures and complete equipment facilities
strictly in accordance with GMP standards, can be used in preclinical and clinical studies hot target
hot target fluorescent molecular probe conclusion
at present, the target fluorescent molecular probe research is still in the initial stage of clinical research, but its effectiveness and feasibility has been proved Its emergence is of great significance for the early diagnosis of cancer and the guidance of surgical tumor removal surgery, and brings considerable benefits to doctors and patients There is still a long way to go, but it is certain that the emergence of targeted fluorescent molecular probes will be a milestone on the road to "precision medicine" and will be an indispensable "black technology" in the entire field of molecular imaging original title: Medical "black technology" attack: target fluorescent molecular probe or change the status quo of tumor diagnosis and treatment