Identification Of Tumor Margins Research Articles

Intraoperative evaluation of tumor margins using a TROP2 near-infrared imaging probe to enable human breast-conserving surgery.

Intraoperative surgical margin assessment remains a challenge during breast-conserving surgery. Here, we report a combined strategy of immuno-positron emission tomography (PET) for preoperative detection of breast cancer and guided assessment of margins in breast-conserving surgery through second near-infrared (NIR-II) fluorescence imaging of trophoblastic cell surface antigen 2 (TROP2). We demonstrated that the intensity of PET signals in the tumors was nearly five times higher than in normal breast tissue with a zirconium-89 tracer conjugated to sacituzumab govitecan (SG) in a mouse spontaneous breast cancer model, enabling the identification of tumors. We further generated a NIR-II probe of indocyanine green conjugated to SG (ICG-SG) and developed a rapid incubation imaging method for intraoperative margin assessment in a relevant time window for the operation workflow. The ICG-SG NIR-II fluorescence image guidance was first verified to remove tumors completely and accurately in mouse breast cancer models. Moreover, the rapid incubation imaging method was applied to distinguish benign and malignant breast lesions in samples from 26 patients with breast cancer. Therefore, we have developed both nuclide and optical probes targeting TROP2 for rapid and precise identification of tumor margins during breast-conserving surgery in humans.

A ratiometric SERS strategy for the prediction of cancer cell proportion and guidance of glioma surgical resection

Rapid and accurate identification of tumor boundaries is critical for the cure of glioma, but it is difficult due to the invasive nature of glioma cells. This paper aimed to explore a rapid diagnostic strategy based on a label-free surface-enhanced Raman scattering (SERS) technique for the quantitative detection of glioma cell proportion intraoperatively. With silver nanoparticles as substrate, an in-depth SERS analysis was performed on simulated clinical samples containing normal brain tissue and different concentrations of patient-derived glioma cells. The results revealed two universal characteristic peaks of 655 and 717 cm−1, which strongly correlated with glioma cell proportion regardless of individual differences. Based on the intensity ratio of the two peaks, a ratiometric SERS strategy for the quantification of glioma cells was established by employing an artificial neuron network model and a polynomial regression model. Such a strategy accurately estimated the proportion of glioma cells in simulated clinical samples (R2 = 0.98) and frozen samples (R2 = 0.85). More importantly, it accurately facilitated the delineation of tumor margins in freshly obtained samples. Taken together, this SERS-based method ensured a rapid and more detailed identification of tumor margins during surgical resection, which could be beneficial for intraoperative decision-making and pathological evaluation.

Rapid evaporative ionization mass spectrometry: A survey through 15 years of applications.

Rapid evaporative ionization mass spectrometry (REIMS) is a relatively recent MS technique explored in many application fields, demonstrating high versatility in the detection of a wide range of chemicals, from small molecules (phenols, amino acids, di- and tripeptides, organic acids, and sugars) to larger biomolecules, that is, phospholipids and triacylglycerols. Different sampling devices were used depending on the analyzed matrix (liquid or solid), resulting in distinct performances in terms of automation, reproducibility, and sensitivity. The absence of laborious and time-consuming sample preparation procedures and chromatographic separations was highlighted as a major advantage compared to chromatographic methods. REIMS was successfully used to achieve a comprehensive sample profiling according to a metabolomics untargeted analysis. Moreover, when a multitude of samples were available, the combination with chemometrics allowed rapid sample differentiation and the identification of discriminant features. The present review aims to provide a survey of literature reports based on the use of such analytical technology, highlighting its mode of operation in different application areas, ranging from clinical research, mostly focused on cancer diagnosis for the accurate identification of tumor margins, to the agri-food sector aiming at the safeguard of food quality and security.

Miniature, multi-dichroic instrument for measuring the concentration of multiple fluorophores.

Identification of tumour margins during resection of the brain is critical for improving the post-operative outcomes. Due to the highly infiltrative nature of glioblastoma multiforme (GBM) and limited intraoperative visualization of the tumour margin, incomplete surgical resection has been observed to occur in up to 80 % of GBM cases, leading to nearly universal tumour recurrence and overall poor prognosis of 14.6 months median survival. This research presents a miniaturized, SiPMT-based optical system for simultaneous measurement of powerful DRS and weak auto-fluorescence for brain tumour detection. The miniaturisation of the optical elements confined the spatial separation of eight select wavelengths into footprint measuring 1.5 × 2 × 16 mm. The small footprint enables this technology to be integrated with existing surgical guidance instruments in the operating room. It's dynamic ability to subtract any background illumination and measure signal intensities across a broad range from pW to mWs make this design much more suitable for clinical environments as compared to spectrometer-based systems with limited dynamic ranges and high integration times. Measurements using optical tissue phantoms containing mixed fluorophores demonstrate correlation coefficients between the fitted response and actual concentration using PLS regression being 0.95, 0.87 and 0.97 for NADH, FAD and PpIX , respectively. These promising results indicate that our proposed miniaturized instrument could serve as an effective alternative in operating rooms, assisting surgeons in identifying brain tumours to achieving positive surgical outcomes for patients.

Molecularly targeted protease-activated probes for visualization of glioblastoma: a comparison with 5-ALA.

The highly infiltrative growth of glioblastoma (GBM) makes distinction between the tumor and normal brain tissue challenging. Therefore, fluorescence-guided surgery is often used to improve visual identification of radiological tumor margins. The aim of this study was to evaluate the ability of recently developed molecularly targeted near-infrared (NIR) protease-activated probes to visualize GBM tissue and to compare the most promising candidate with the gold standard, 5-aminolevulinic acid (5-ALA). Single-substrate probes 6QC-ICG and 6QC-Cy5 (cysteine cathepsin cleavable), double-substrate probes AG2-FNIR and AG2-Cy5 (cysteine cathepsin and caspase 3 cleavable), and 5-ALA were administered intravenously to mice with orthotopic tumors. Activation of the probes was also evaluated in cell cultures in vitro and in biopsy material from patients with GBM ex vivo. The tumor to normal brain tissue fluorescence ratio (TNR) was quantified in brain sections using preclinical and clinical visualization platforms, and in tissue homogenates and cell suspensions using spectrofluorimetry. Subcellular localization of the fluorophores was visualized by confocal microscopy. In vitro, the single-substrate probe 6QC-ICG was cleaved in glioma cells and macrophages, and the resulting fluorophore accumulated intracellularly. In experimental GBMs, both single- and double-substrate probes visualized tumor tissue, while in healthy brain tissue the signal was minimal. TNR was highest for 6QC-ICG and AG2-FNIR, but the signal intensity was higher for 6QC-ICG. Using xenograft and syngeneic mouse models, as well as human GBM biopsy material ex vivo, the authors confirmed the ability of 6QC-ICG to specifically visualize the glioma tissue using preclinical and clinical visualization platforms. Finally, a comparison with 5-ALA in animals coadministered with both compounds revealed a higher TNR for 6QC-ICG in experimental GBMs. The cysteine cathepsin-cleavable probe 6QC-ICG is activated by glioma cells and tumor-associated macrophages, leading to a high contrast between tumor and nontumorous brain tissue that is superior to that of the current standard, 5-ALA. In addition to a well-defined mechanism of action, protease-activated probes that use NIR fluorophores (e.g., indocyanine green) have the advantage of low absorption and scattering of the NIR light and lower tissue autofluorescence. These results suggest that 6QC-ICG has the potential to become the targeted agent in intraoperative detection of GBM tissue using fluorescence imaging.

Сравнение липидных изменений в астроцитомах по мере роста их злокачественности

The use of ambient ionization mass spectrometry methods is one of the promising approaches to the impovement of glial tumor resection completeness by using an additional method to improve the tumor margin identification accuracy during the neurosurgical intervention itself. The amounts of data accumulated when testing such techniques can be also used in fundamental research to identify metabolic alterations associated with the tumor growth. The study was aimed to assess changes in the cell membrane lipid composition of diffuse and anaplastic astrocytomas based on the data acquired by ambient ionization mass spectrometry profiling of the tissues excised during the elective neurosurgical intervention. The lipid profiles obtained when assessing the tumor tissue samples (n = 43) by flow microextraction in a cartridge were subjected to shrinkage linear discriminant analysis enabling extraction of a number of lipids, the levels of which changed with increasing tumor grade. The lipid diversity decreased with increasing grade. Thus, the levels of 13 phospholipids belonging to six different subclasses turned out to be decreased in anaplastic tumors compared to diffuse ones. Both average size of the polar lipid fatty acid residues and their degree of unsaturation decrease with increasing tumor grade. The findings agree well with the data of the earlier study of high-grade glial tumors and confirm the biochemical view of metabolic reprogramming associated with malignant transformation of neuroglia.

Precise and safe pulmonary segmentectomy enabled by visualizing cancer margins with dual-channel near-infrared fluorescence.

Segmentectomy is a type of limited resection surgery indicated for patients with very early-stage lung cancer or compromised function because it can improve quality of life with minimal removal of normal tissue. For segmentectomy, an accurate detection of the tumor with simultaneous identification of the lung intersegment plane is critical. However, it is not easy to identify both during surgery. Here, the authors report dual-channel image-guided lung cancer surgery using renally clearable and physiochemically stable targeted fluorophores to visualize the tumor and intersegmental plane distinctly with different colors; cRGD-ZW800 (800nm channel) targets tumors specifically, and ZW700 (700nm channel) simultaneously helps discriminate segmental planes. The near-infrared (NIR) fluorophores with 700nm and with 800nm channels were developed and evaluated the feasibility of dual-channel fluorescence imaging of lung tumors and intersegmental lines simultaneously in mouse, rabbit, and canine animal models. Expression levels of integrin αvβ3, which is targeted by cRGD-ZW800-PEG, were retrospectively studied in the lung tissue of 61 patients who underwent lung cancer surgery. cRGD-ZW800-PEG has clinically useful optical properties and outperforms the FDA-approved NIR fluorophore indocyanine green and serum unstable cRGD-ZW800-1 in multiple animal models of lung cancer. Combined with the blood-pooling agent ZW700-1C, cRGD-ZW800-PEG permits dual-channel NIR fluorescence imaging for intraoperative identification of lung segment lines and tumor margins with different colors simultaneously and accurately. This dual-channel image-guided surgery enables complete tumor resection with adequate negative margins that can reduce the recurrence rate and increase the survival rate of lung cancer patients.

Dual Tumor-Selective β-Carboline-Based Fluorescent Probe for High-Contrast/Rapid Diagnosis of Clinical Tumor Tissues.

Given that precise/rapid intraoperative tumor margin identification is still challenging, novel fluorescent probes HY and HYM, based on acidic tumor microenvironment (TME) activation and organic anion transporting polypeptide (OATPs)-mediated selective uptake, were constructed and synthesized. Both of them possessed acidic pH-activatable and reversible fluorescence as well as large Stokes shift. Compared with HY, HYM had a higher (over 9-fold) enhancement in fluorescence with pH ranging from 7.6 to 4.0, and the fluorescence quantum yield of HYM (ΦF = 0.49) at pH = 4.0 was 8-fold stronger than that (ΦF = 0.06) at pH = 7.4. Mechanism research demonstrated that acidic TME-induced protonation of the pyridine N atom on β-carbolines accounted for the pH-sensitive fluorescence by influencing the intramolecular charge transfer (ICT) effect. Furthermore, HYM selectively lit up cancer cells and tumor tissues not only by "off-on" fluorescence but also by OATPs (overexpressed on cancer cells)-mediated cancer cellular internalization, offering dual tumor selectivity for precise visualization of tumor mass and intraoperative guidance upon in situ spraying. Most importantly, HYM enabled rapid and high-contrast (tumor-to-normal tissue ratios > 6) human tumor margin identification in clinical tumor tissues by simple spraying within 6 min, being promising for aiding in clinical surgical resection.

High-contrast tumor imaging via a de novo designed aminopeptidase N targeted fluorogenic probe

Cancer, a leading cause of death worldwide, still needs surgery as essential curation in over 80% population. However, complete resection of cancerous tissues remains a great challenge due to the difficulty in tumor margin identification. Fluorescent probe based imaged-guided surgery (IGS) for in-situ local disease focus imaging is thought to be an ideal method for intraoperation tumor identification due to its high spatiotemporal resolution and real-time manner. By targeting tumor microenvironments (TME) or tumor-associated biomolecules, fluorescent probes could “light-up” tumor tissues and navigate surgical operation. Among which, biosensors targeting aminopeptidase N (APN) have attracted intense attention due to its high relevance with progression of tumor. However, most of the probes adopting its natural substrate (L-Alaine) as the recognition unit may be vulnerable toward other widely distributed aminopeptidase such as leukotriene A4 hydrolase (LTA4H) and leucine aminopeptidase (LAP). In order to acquire high specific APN targeted probe for accurate detection of APN activity in biological samples and fulfill high contrast tumor imaging, herein a non-natural amino acid (P-Chloro-L-Phenylalanine, PCPA) based fluorescent probe was firstly reported for APN targeted bioimaging. The acquired named as TMN-PCPA showed high affinity (Km = 3.27 ± 0.23 μM) and dramatically improved selectivity toward APN than previously reported APN probe. TMN-PCPA was successfully applicated into discrimination tumor bio-samples from normal bio-samples in both cellular and ex vivo level with significantly increased tumor to normal (T/N) ratio, thus showed great potential in intraoperation application such imaged-guided surgery and providing structural basis to high specific APN targeted biosensor construction.

The Multifaceted Role of Confocal Laser Endomicroscopy in Head and Neck Surgery: Oncologic and Functional Insights.

(1) Background: Confocal laser endomicroscopy (CLE) has emerged as a transformative tool in head and neck surgery, with applications spanning oncologic insights and functional evaluations. This study delves into CLE's potential in these domains. (2) Methods: We performed CLE in head and neck oncologic surgery, focusing on tumor margin identification and precise resection. We also employed CLE for functional assessment in allergic rhinitis, observing real-time mucosal changes during nasal provocation testing. (3) Results: In oncologic surgery, CLE enabled real-time visualization of tumor margins and cellular patterns, aiding resection decisions. In allergic rhinitis assessment, CLE captured dynamic morphological alterations upon allergen exposure, enhancing understanding of mucosal reactions. (4) Conclusions: The integration of CLE with evolving technologies such as deep learning and AI holds promise for enhanced diagnostic accuracy. This study underscores CLE's expansive potential, highlighting its role in guiding surgical choices and illuminating inflammatory processes in the head and neck.

Deep learning for tumor margin identification in electromagnetic imaging

In this work, a novel method for tumor margin identification in electromagnetic imaging is proposed to optimize the tumor removal surgery. This capability will enable the visualization of the border of the cancerous tissue for the surgeon prior or during the excision surgery. To this end, the border between the normal and tumor parts needs to be identified. Therefore, the images need to be segmented into tumor and normal areas. We propose a deep learning technique which divides the electromagnetic images into two regions: tumor and normal, with high accuracy. We formulate deep learning from a perspective relevant to electromagnetic image reconstruction. A recurrent auto-encoder network architecture (termed here DeepTMI) is presented. The effectiveness of the algorithm is demonstrated by segmenting the reconstructed images of an experimental tissue-mimicking phantom. The structure similarity measure (SSIM) and mean-square-error (MSE) average of normalized reconstructed results by the DeepTMI method are about 0.94 and 0.04 respectively, while that average obtained from the conventional backpropagation (BP) method can hardly overcome 0.35 and 0.41 respectively.

Precise tumor delineation in clinical tissues using a novel acidic tumor microenvironment activatable near-infrared fluorescent contrast agent

Tumor selective near-infrared (NIR) fluorescent contrast agents has the potential to greatly enhance the efficiency and precision of tumor surgery by enabling real-time tumor margin identification for tumor resection guided by imaging. However, the development of these agents is still challenging. In this study, based on the acidic tumor microenvironment (TME), we designed and synthesized a novel pH-sensitive NIR fluorescent contrast agent OBD from β-carboline. The fluorescence quantum yield of OBD exhibited a notable increase at pH 3.6, approximately 12-fold higher compared to its value at pH 7.4. After cellular uptake, OBD lighted up the cancer cells with high specificity and accumulated in the mitochondria. Spraying OBD emitted selective fluorescence in xenograft tumor tissues with tumor-to-normal tissue ratios (TNR) as high as 11.18, implying successful image-guided surgery. Furthermore, OBD was also shown to track metastasis in spray mode. After simple topical spray, OBD rapidly and precisely visualized the tumor margins of clinical colon and liver tissues with TNR over 4.2. Therefore, the small-molecule fluorescent contrast agent OBD has promising clinical applications in tumor identification during surgery.

Three-Dimensional Histological Electrophoresis for High-Throughput Cancer Margin Detection in Multiple Types of Tumor Specimens.

Accurate identification of tumor margins during cancer surgeries relies on a rapid detection technique that can perform high-throughput detection of multiple suspected tumor lesions at the same time. Unfortunately, the conventional histopathological analysis of frozen tissue sections, which is considered the gold standard, often demonstrates considerable variability, especially in many regions without adequate access to trained pathologists. Therefore, there is a clinical need for a multitumor-suitable complementary tool that can accurately and high-throughput assess tumor margins in every direction within the surgically resected tissue. We herein describe a high-throughput three-dimensional (3D) histological electrophoresis device that uses tumor-specific proteins to identify and contour tumor margins intraoperatively. Testing on seven cell-line xenograft models and human cervical cancer models (representing five types of tissues) demonstrated the high-throughput detection utility of this approach. We anticipate that the 3D histological electrophoresis device will improve the accuracy and efficiency of diagnosing a wide range of cancers.

Robot-Guided Ultrasonography in Surgical Interventions.

The introduction of robotic-guided procedures in surgical techniques has brought an increase in the accuracy and control of resections. Surgery has evolved as a technique since the development of laparoscopy, which has added to the visualisation of the peritoneal cavity from a different perspective. Multi-armed robot associated with real-time intraoperative imaging devices brings important manoeuvrability and dexterity improvements in certain surgical fields. The present study is designed to synthesise the development of imaging techniques with a focus on ultrasonography in robotic surgery in the last ten years regarding abdominal surgical interventions. All studies involved abdominal surgery. Out of the seven studies, two were performed in clinical trials. The other five studies were performed on organs or simulators and attempted to develop a hybrid surgical technique using ultrasonography and robotic surgery. Most studies aim to surgically identify both blood vessels and nerve structures through this combined technique (surgery and imaging). Ultrasonography is often used in minimally invasive surgical techniques. This adds to the visualisation of blood vessels, the correct identification of tumour margins, and the location of surgical instruments in the tissue. The development of ultrasound technology from 2D to 3D and 4D has brought improvements in minimally invasive and robotic surgical techniques, and it should be further studied to bring surgery to a higher level.

Intraoperative Imaging in Hepatopancreatobiliary Surgery.

Hepatopancreatobiliary surgery belongs to one of the most complex fields of general surgery. An intricate and vital anatomy is accompanied by difficult distinctions of tumors from fibrosis and inflammation; the identification of precise tumor margins; or small, even disappearing, lesions on currently available imaging. The routine implementation of ultrasound use shifted the possibilities in the operating room, yet more precision is necessary to achieve negative resection margins. Modalities utilizing fluorescent-compatible dyes have proven their role in hepatopancreatobiliary surgery, although this is not yet a routine practice, as there are many limitations. Modalities, such as photoacoustic imaging or 3D holograms, are emerging but are mostly limited to preclinical settings. There is a need to identify and develop an ideal contrast agent capable of differentiating between malignant and benign tissue and to report on the prognostic benefits of implemented intraoperative imaging in order to navigate clinical translation. This review focuses on existing and developing imaging modalities for intraoperative use, tailored to the needs of hepatopancreatobiliary cancers. We will also cover the application of these imaging techniques to theranostics to achieve combined diagnostic and therapeutic potential.

Early results of minimally invasive fluorescent guided pediatric oncology surgery with delivery of indocyanine green during induction of anesthesia

BackgroundIndocyanine green (ICG) fluoresces in the near infra-red (NIR) spectrum. It is widely used in adult oncological surgery for identification of tumor margins and lymph node sampling. However, deliver of ICG in almost all studies is 24 h or more prior to surgery. This is the first study in children to assess its feasibility in minimally invasive surgery (MIS) for oncological disease following ICG injection during induction of anesthesia. MethodsThis was an open label, prospective, single center, feasibility study recruiting consecutive patients eligible for MIS tumor resection or metastectomy. ICG was injected intravenously at induction of anesthesia. Patient demographics, intraoperative appearances, post-operative histopathology, and surgeon Likert ratings were collected. ResultsFourteen patients were included. Five had lung metastases (Wilms, Osteosarcoma (2), Hodgkin's, melanoma) and 9 had other tumors (neuroblastoma, inflammatory myofibroblastic tumor, ganglioneuroma, phaeochromocytoma, adrenal tumor). Lung metastases were easily identifiable, and all had negative margins. Tumors containing viable disease fluoresced and were completely resected, whilst benign and heavily treated tumors were afluorescent. There were no adverse events relating to ICG or issues with background fluorescence. ConclusionBased on this small sample, injection of ICG during induction of anesthesia is safe and effective in showing tumor margins in patients who have had little or no neoadjuvant chemotherapy as well as in metastectomy in Wilms and osteosarcoma. Further studies are needed to confirm these preliminary results.

Acidic tumor microenvironment-activatable fluorescent diagnostic probe for the rapid identification and resection of human tumors via spraying

A fluorescent diagnostic probe for real-time intraoperative image-guided tumor resection can significantly improve the efficiency and quality of oncological therapy, but their development is challenging. Herein, a novel fluorescent diagnostic probe called HLTC based on β-carboline was designed and synthesized. HLTC was found to show a ∼10-fold enhancement of fluorescence quantum field with pH from 7.4 to 4.0, indicating its imaging potential in acid environment which is a typical hallmark of the tumor microenvironment (TME). Following fluorescence microscopy imaging showed HLTC could emit specific signals in cancer cells and sections, by both one-photon excitation and two-photon excitation. Importantly, HLTC enabled the precise and rapid delineation of both transplanted tumor and clinical tumor tissues within several minutes of simple topical spray. The tumor-to-background ratio (TBR) was up to 10.2 ± 1.0 at clinical liver cancer tissues and 9.9 ± 0.3 at clinical colon cancer tissues, allowing precise tumor margin identification and the effective guidance of surgical tumor resection. Furthermore, CCK8 assay, pharmacokinetic evaluation, blood analysis and H&E staining were performed, which verified high biocompatibility and biosafety of HLTC at working concentration. These results reveal the exciting potential of this small-molecule fluorescent diagnostic probe for real-time fluorescence-based navigation during surgical tumor resection.

Towards OCT-Guided Endoscopic Laser Surgery—A Review

Optical Coherence Tomography (OCT) is an optical imaging technology occupying a unique position in the resolution vs. imaging depth spectrum. It is already well established in the field of ophthalmology, and its application in other fields of medicine is growing. This is motivated by the fact that OCT is a real-time sensing technology with high sensitivity to precancerous lesions in epithelial tissues, which can be exploited to provide valuable information to clinicians. In the prospective case of OCT-guided endoscopic laser surgery, these real-time data will be used to assist surgeons in challenging endoscopic procedures in which high-power lasers are used to eradicate diseases. The combination of OCT and laser is expected to enhance the detection of tumors, the identification of tumor margins, and ensure total disease eradication while avoiding damage to healthy tissue and critical anatomical structures. Therefore, OCT-guided endoscopic laser surgery is an important nascent research area. This paper aims to contribute to this field with a comprehensive review of state-of-the-art technologies that may be exploited as the building blocks for achieving such a system. The paper begins with a review of the principles and technical details of endoscopic OCT, highlighting challenges and proposed solutions. Then, once the state of the art of the base imaging technology is outlined, the new OCT-guided endoscopic laser surgery frontier is reviewed. Finally, the paper concludes with a discussion on the constraints, benefits and open challenges associated with this new type of surgical technology.

Novel pH-activatable NIR fluorogenic spray mediated near-instant and precise tumor margins identification in human cancer tissues for surgical resection.

Rationale: Challenges such as developing a universal tumor-specific probe for tumor margin identification in diverse tumors with an easy-operative and fast-imaging pattern still exist. Hence, in the present study, a rapidly "off-on" near-infrared (NIR) fluorescent probe NBD with pH-activatable fluorescence and a large Stokes shift was constructed for spray mediated near-instant and precise clinical tumor margins identification. Methods: NBD was designed and synthesized by introducing both diphenyl amino group and benzo[e]indolium to β-carboline at C-6 and C-3 positions respectively. The optical properties of NBD was characterized by absorption spectra, fluorescence spectra. Subsequently, we investigated its pH-dependent mechanism by 1H NMR and density functional theory (DFT) calculation. NBD was further under deeper investigation into its imaging performance in nude mice models (subcutaneous, orthotopic, metastatic tumor), and clinical tissues from patients with three clinically representative tumors (liver cancer, colon cancer, and lung cancer). Results: It was found that NBD had NIR fluorescence (742 nm), a large Stokes shift (160 nm), and two-photon absorbance (1040 nm). Fluorescence quantum yield (ФF) increased by 5.5-fold when pH decreased from 7.4 to 4.0, to show pH-dependent property. Furthermore, NBD could not only selectively light up all four cancer cell lines, but also delineate xenograft tumor and orthotopic microtumor to guide surgical tumor resection, and track metastatic tissues. Particularly, after simple topical spray (three minutes later), NBD could rapidly and precisely distinguish the boundary ranges of three kinds of clinical cancer specimens including liver, colon, and lung cancers, with high tumor-to-normal tissue signal ratios (6.48~9.80). Conclusions: Therefore, the proposed fluorescent probe NBD may serve as a versatile NIR fluorogenic spray for the near-instant visualization of tumor margins and assisting surgeons in surgerical resection of clinical cancers.

Application of near-infrared fluorescence imaging in theranostics of gastrointestinal tumors.

Gastrointestinal cancers have become an important cause of cancer-related death in humans. Improving the early diagnosis rate of gastrointestinal tumors and improving the effect of surgical treatment can significantly improve the survival rate of patients. The conventional diagnostic method is high-definition white-light endoscopy, which often leads to missed diagnosis. For surgical treatment, intraoperative tumor localization and post-operative anastomotic state evaluation play important roles in the effect of surgical treatment. As a new imaging method, near-infrared fluorescence imaging (NIRFI) has its unique advantages in the diagnosis and auxiliary surgical treatment of gastrointestinal tumors due to its high sensitivity and the ability to image deep tissues. In this review, we focus on the latest advances of NIRFI technology applied in early diagnosis of gastrointestinal tumors, identification of tumor margins, identification of lymph nodes, and assessment of anastomotic leakage. In addition, we summarize the advances of NIRFI systems such as macro imaging and micro imaging systems, and also clearly describe the application process of NIRFI from system to clinical application, and look into the prospect of NIRFI applied in the theranostics of gastrointestinal tumors.