Application value of indocyanine green fluorescence imaging in guiding sentinel lymph node biopsy diagnosis of gastric cancer: Meta-analysis.

BACKGROUND: Gastric cancer is a common malignant tumor of the digestive system worldwide, and its early diagnosis is crucial to improve the survival rate of patients. Indocyanine green fluorescence imaging (ICG-FI), as a new imaging technology, has shown potential application prospects in oncology surgery. The meta-analysis to study the application value of ICG-FI in the diagnosis of gastric cancer sentinel lymph node biopsy is helpful to comprehensively evaluate the clinical effect of this technology and provide more reliable guidance for clinical practice. AIM: To assess the diagnostic efficacy of optical imaging in conjunction with indocyanine green (ICG)-guided sentinel lymph node (SLN) biopsy for gastric cancer. METHODS: Electronic databases such as PubMed, Embase, Medline, Web of Science, and the Cochrane Library were searched for prospective diagnostic tests of optical imaging combined with ICG-guided SLN biopsy. Stata 12.0 software was used for analysis by combining the "bivariable mixed effect model" with the "midas" command. The true positive value, false positive value, false negative value, true negative value, and other information from the included literature were extracted. A literature quality assessment map was drawn to describe the overall quality of the included literature. A forest plot was used for heterogeneity analysis, and P < 0.01 was considered to indicate statistical significance. A funnel plot was used to assess publication bias, and P < 0.1 was considered to indicate statistical significance. The summary receiver operating characteristic (SROC) curve was used to calculate the area under the curve (AUC) to determine the diagnostic accuracy. If there was interstudy heterogeneity (I 2 > 50%), meta-regression analysis and subgroup analysis were performed. RESULTS: Optical imaging involves two methods: Near-infrared (NIR) imaging and fluorescence imaging. A combination of optical imaging and ICG-guided SLN biopsy was useful for diagnosis. The positive likelihood ratio was 30.39 (95%CI: 0.92-1.00), the sensitivity was 0.95 (95%CI: 0.82-0.99), and the specificity was 1.00 (95%CI: 0.92-1.00). The negative likelihood ratio was 0.05 (95%CI: 0.01-0.20), the diagnostic odds ratio was 225.54 (95%CI: 88.81-572.77), and the SROC AUC was 1.00 (95%CI: The crucial values were sensitivity = 0.95 (95%CI: 0.82-0.99) and specificity = 1.00 (95%CI: 0.92-1.00). The Deeks method revealed that the "diagnostic odds ratio" funnel plot of SLN biopsy for gastric cancer was significantly asymmetrical (P = 0.01), suggesting significant publication bias. Further meta-subgroup analysis revealed that, compared with fluorescence imaging, NIR imaging had greater sensitivity (0.98 vs 0.73). Compared with optical imaging immediately after ICG injection, optical imaging after 20 minutes obtained greater sensitivity (0.98 vs 0.70). Compared with that of patients with an average SLN detection number < 4, the sensitivity of patients with a SLN detection number ≥ 4 was greater (0.96 vs 0.68). Compared with hematoxylin-eosin (HE) staining, immunohistochemical (+ HE) staining showed greater sensitivity (0.99 vs 0.84). Compared with subserous injection of ICG, submucosal injection achieved greater sensitivity (0.98 vs 0.40). Compared with 5 g/L ICG, 0.5 and 0.05 g/L ICG had greater sensitivity (0.98 vs 0.83), and cT1 stage had greater sensitivity (0.96 vs 0.72) than cT2 to cT3 clinical stage. Compared with that of patients ≤ 26, the sensitivity of patients > 26 was greater (0.96 vs 0.65). Compared with the literature published before 2010, the sensitivity of the literature published after 2010 was greater (0.97 vs 0.81), and the differences were statistically significant (all P < 0.05). CONCLUSION: For the diagnosis of stomach cancer, optical imaging in conjunction with ICG-guided SLN biopsy is a therapeutically viable approach, especially for early gastric cancer. The concentration of ICG used in the SLN biopsy of gastric cancer may be too high. Moreover, NIR imaging is better than fluorescence imaging and may obtain higher sensitivity.

Revisiting the standards of cancer detection and therapy alongside their comparison to modern methods.

In accordance with the World Health Organization data, cancer remains at the forefront of fatal diseases. An upward trend in cancer incidence and mortality has been observed globally, emphasizing that efforts in developing detection and treatment methods should continue. The diagnostic path typically begins with learning the medical history of a patient; this is followed by basic blood tests and imaging tests to indicate where cancer may be located to schedule a needle biopsy. Prompt initiation of diagnosis is crucial since delayed cancer detection entails higher costs of treatment and hospitalization. Thus, there is a need for novel cancer detection methods such as liquid biopsy, elastography, synthetic biosensors, fluorescence imaging, and reflectance confocal microscopy. Conventional therapeutic methods, although still common in clinical practice, pose many limitations and are unsatisfactory. Nowadays, there is a dynamic advancement of clinical research and the development of more precise and effective methods such as oncolytic virotherapy, exosome-based therapy, nanotechnology, dendritic cells, chimeric antigen receptors, immune checkpoint inhibitors, natural product-based therapy, tumor-treating fields, and photodynamic therapy. The present paper compares available data on conventional and modern methods of cancer detection and therapy to facilitate an understanding of this rapidly advancing field and its future directions. As evidenced, modern methods are not without drawbacks; there is still a need to develop new detection strategies and therapeutic approaches to improve sensitivity, specificity, safety, and efficacy. Nevertheless, an appropriate route has been taken, as confirmed by the approval of some modern methods by the Food and Drug Administration.

Porphyrin-Based Organic Nanoparticles with NIR-IIa Fluorescence for Orthotopic Glioblastoma Theranostics.

The development of efficient theranostic nanoagents for the precise diagnosis and targeted therapy of glioblastoma (GBM) remains a big challenge. Herein, we designed and developed porphyrin-based organic nanoparticles (PNP NPs) with strong emission in the near-infrared IIa window (NIR-IIa) for orthotopic GBM theranostics. PNP NPs possess favorable photoacoustic and photothermal properties, high photostability, and low toxicity. After modification with the RGD peptide, the obtained PNPD NPs exhibited enhanced blood-brain barrier (BBB) penetration capability and GBM targeting ability. NIR-IIa imaging was employed to monitor the in vivo biodistribution and accumulation of the nanoparticles, revealing a significant enhancement in penetration depth and signal-to-noise ratio. Both in vitro and in vivo results demonstrated that PNPD NPs effectively inhibited the proliferation of tumor cells and induced negligible side effects in normal brain tissues. In general, the work presented a kind of brain-targeted porphyrin-based NPs with NIR-IIa fluorescence for orthotopic glioblastoma theranostics, showing promising prospects for clinical translation.

Predicting in vivo therapeutic efficacy of CelTrac1000-labeled hair follicle epidermal neural crest stem cells in models of repairing rat facial nerve defects via second near-infrared fluorescence imaging.

AIMS: To detect the therapeutic efficacy of CelTrac1000-labeled hair follicle epidermal neural crest stem cells (EPI-NCSCs) on repairing facial nerve defects by second near-infrared (NIR-II) fluorescence imaging. MATERIALS AND METHODS: Firstly, CelTrac1000-labeled EPI-NCSCs were microinjected into the acellular nerve allografts (ANAs) to bridge a 10-mm-long gap in the buccal branch of facial nerve in adult rats. Then, Celtrac1000-labeled EPI-NCSCs were detected by NIR-II fluorescence imaging system to visualize the behavior of the transplanted cells in vivo. Additionally, the effect of the transplanted EPI-NCSCs on repairing facial nerve defect was examined. KEY FINDINGS: Through 14 weeks of dynamic observation, the transplanted EPI-NCSCs survived in the ANAs in vivo after surgery. Meanwhile, the region of the NIR-II fluorescence signals was gradually limited to be consistent with the direction of the regenerative nerve segment. Furthermore, the results of functional and morphological analysis showed that the transplanted EPI-NCSCs could promote the recovery of facial paralysis and neural regeneration after injury. SIGNIFICANCE: Our research provides a novel way to track the transplanted cells in preclinical studies of cell therapy for facial paralysis, and demonstrates the therapeutic potential of EPI-NCSCs combined with ANAs in bridging rat facial nerve defects.

The role of ureteric indocyanine green fluorescence in colorectal surgery: a retrospective cohort study.

BACKGROUND: Ureteric injury (UI) is an infrequent but serious complication of colorectal surgery. Prophylactic ureteric stenting is employed to avoid UI, yet its efficacy remains debated. Intraoperative indocyanine green fluorescence imaging (ICG-FI) has been used to facilitate ureter detection. This study aimed to investigate the role of ICG-FI in identification of ureters during colorectal surgery and its impact on the incidence of UI. METHODS: A retrospective cohort study involving 556 consecutive patients who underwent colorectal surgery between 2018 and 2023 assessed the utility of routine prophylactic ureteric stenting with adjunctive ICG-FI. Patients with ICG-FI were compared to those without ICG-FI. Demographic data, operative details, and postoperative morbidity were analyzed. Statistical analysis included univariable regression. RESULTS: Ureteric ICG-FI was used in 312 (56.1%) patients, whereas 43.9% were controls. Both groups were comparable in terms of demographics except for a higher prevalence of prior abdominal surgeries in the ICG-FI group. Although intraoperative visualization was significantly higher in the ICG-FI group (95.3% vs 89.1%; p = 0.011), the incidence of UI was similar between groups (0.3% vs 0.8%; p = 0.585). Postoperative complications were similar between the two groups. Median stent insertion time was longer in the ICG-FI group (32 vs 25 min; p = 0.001). CONCLUSION: Ureteric ICG-FI improved intraoperative visualization of the ureters but was not associated with a reduced UI rate. Median stent insertion time increased with use of ureteric ICG-FI, but total operative time did not. Despite its limitations, this study is the largest of its kind suggesting that ureteric ICG-FI may be a valuable adjunct to facilitate  ureteric visualization during colorectal surgery.

Fluorescence in neurosurgery: its therapeutic and diagnostic significance - a comprehensive review.

This review provides a comprehensive overview of the therapeutic and diagnostic implications of fluorescence imaging in neurosurgery. Fluorescence imaging has become a valuable intraoperative visualization and guidance tool, facilitating precise surgical interventions. The therapeutic role of fluorescence is examined, including its application in photodynamic therapy and tumor-targeted therapy. It also explores its diagnostic capabilities in tumor detection, margin assessment, and blood-brain barrier evaluation. Drawing from clinical and preclinical studies, the review underscores the growing evidence supporting the efficacy of fluorescence imaging in neurosurgical practice. Furthermore, it discusses current limitations and future directions, emphasizing the potential for emerging technologies to enhance the utility and accessibility of fluorescence imaging, ultimately improving patient outcomes in neurosurgery.

Devices and Methods for Dosimetry of Personalized Photodynamic Therapy of Tumors: A Review on Recent Trends.

Significance: Despite the widespread use of photodynamic therapy in clinical practice, there is a lack of personalized methods for assessing the sufficiency of photodynamic exposure on tumors, depending on tissue parameters that change during light irradiation. This can lead to different treatment results. Aim: The objective of this article was to conduct a comprehensive review of devices and methods employed for the implicit dosimetric monitoring of personalized photodynamic therapy for tumors. Methods: The review included 88 peer-reviewed research articles published between January 2010 and April 2024 that employed implicit monitoring methods, such as fluorescence imaging and diffuse reflectance spectroscopy. Additionally, it encompassed computer modeling methods that are most often and successfully used in preclinical and clinical practice to predict treatment outcomes. The Internet search engine Google Scholar and the Scopus database were used to search the literature for relevant articles. Results: The review analyzed and compared the results of 88 peer-reviewed research articles presenting various methods of implicit dosimetry during photodynamic therapy. The most prominent wavelengths for PDT are in the visible and near-infrared spectral range such as 405, 630, 660, and 690 nm. Conclusions: The problem of developing an accurate, reliable, and easily implemented dosimetry method for photodynamic therapy remains a current problem, since determining the effective light dose for a specific tumor is a decisive factor in achieving a positive treatment outcome.

Noninvasive Diagnostic Method to Objectively Measure Olfaction and Diagnose Smell Disorders by a Molecularly Targeted Fluorescence Imaging Agent.

Despite the recent advances in understanding the mechanisms of olfaction, no tools are currently available to noninvasively identify loss of smell. Because of the substantial increase in patients presenting with coronavirus disease 2019-related loss of smell, the pandemic has highlighted the urgent need to develop quantitative methods. Methods: Our group investigated the use of a novel fluorescent probe named Tsp1a-IR800P as a tool to diagnose loss of smell. Tsp1a-IR800P targets sodium channel 1.7, which plays a critical role in olfaction by aiding the signal propagation to the olfactory bulb. Results: Intuitively, we have identified that conditions leading to loss of smell, including chronic inflammation and coronavirus disease 2019, correlate with the downregulation of sodium channel 1.7 expression in the olfactory epithelium, both at the transcript and at the protein levels. We demonstrated that lower Tsp1a-IR800P fluorescence emissions significantly correlate with loss of smell in live animals-thus representing a potential tool for its semiquantitative assessment. Currently available methods rely on delayed subjective behavioral studies. Conclusion: This method could aid in significantly improving preclinical and clinical studies by providing a way to objectively diagnose loss of smell and therefore aid the development of therapeutic interventions.

A Wireless, Multicolor Fluorescence Image Sensor Implant for Real-Time Monitoring in Cancer Therapy.

Real-time monitoring of dynamic biological processes in the body is critical to understanding disease progression and treatment response. This data, for instance, can help address the lower than 50% response rates to cancer immunotherapy. However, current clinical imaging modalities lack the molecular contrast, resolution, and chronic usability for rapid and accurate response assessments. Here, we present a fully wireless image sensor featuring a 2.5×5 mm2 CMOS integrated circuit for multicolor fluorescence imaging deep in tissue. The sensor operates wirelessly via ultrasound (US) at 5 cm depth in oil, harvesting energy with 221 mW/cm2 incident US power density (31% of FDA limits) and backscattering data at 13 kbps with a bit error rate <10-6. In-situ fluorescence excitation is provided by micro-laser diodes controlled with a programmable on-chip driver. An optical frontend combining a multi-bandpass interference filter and a fiber optic plate provides >6 OD excitation blocking and enables three-color imaging for detecting multiple cell types. A 36×40-pixel array captures images with <125 µm resolution. We demonstrate wireless, dual-color fluorescence imaging of both effector and suppressor immune cells in ex vivo mouse tumor samples with and without immunotherapy. These results show promise for providing rapid insight into therapeutic response and resistance, guiding personalized medicine.

Development of a Highly Specific Fluorescent Probe based on Thiol-ene Click Nucleophilic Cascade Reactions for Delving into the Action Mechanism of Serotonin in Depression.

The intrinsic correlation between depression and serotonin (5-HT) is a highly debated topic, with significant implications for the diagnosis, treatment, and advancement of drugs targeting neurological disorders. To address this important question, it is of utmost priority to understand the action mechanism of serotonin in depression through fluorescence imaging studies. However, the development of efficient molecular probes for serotonin is hindered by the lack of responsive sites with high selectivity for serotonin at the present time. Herein, we developed the first highly selective serotonin responsive site, 3-mercaptopropionate, utilizing thiol-ene click cascade nucleophilic reactions. The novel responsive site was then employed to construct the powerful molecular probe SJ-5-HT for imaging the serotonin level changes in the depression cells and brain tissues. Importantly, the imaging studies reveal that the level of serotonin in patients with depression may not be the primary factor, while the ability of neurons in patients with depression to release serotonin appears to be more critical. Additionally, this serotonin release capability correlates strongly with the levels of mTOR (intracellular mammalian target of rapamycin). These discoveries could offer valuable insights into the molecular mechanisms underpinning depression and furnish mTOR as a novel direction for the advancement of antidepressant therapies.

A 3D Pancreatic Cancer Model with Integrated Optical Sensors for Noninvasive Metabolism Monitoring and Drug Screening.

A distinct feature of pancreatic ductal adenocarcinoma (PDAC) is a prominent tumor microenvironment (TME) with remarkable cellular and spatial heterogeneity that meaningfully impacts disease biology and treatment resistance. The dynamic crosstalk between cancer cells and the dense stromal compartment leads to spatially and temporally heterogeneous metabolic alterations, such as acidic pH that contributes to drug resistance in PDAC. Thus, monitoring the extracellular pH metabolic fluctuations within the TME is crucial to predict and to quantify anticancer drug efficacy. Here, a simple and reliable alginate-based 3D PDAC model embedding ratiometric optical pH sensors and cocultures of tumor (AsPC-1) and stromal cells for simultaneously monitoring metabolic pH variations and quantify drug response is presented. By means of time-lapse confocal laser scanning microscopy (CLSM) coupled with a fully automated computational analysis, the extracellular pH metabolic variations are monitored and quantified over time during drug testing with gemcitabine, folfirinox, and paclitaxel, commonly used in PDAC therapy. In particular, the extracellular acidification is more pronounced after drugs treatment, resulting in increased antitumor effect correlated with apoptotic cell death. These findings highlight the importance of studying the influence of cellular metabolic mechanisms on tumor response to therapy in 3D tumor models, this being crucial for the development of personalized medicine approaches.

Investigation of the substituent effect of indocyanine green derivatives for lymph imaging.

Fluorescence lymph imaging with indocyanine green (ICG) is widely utilized as diagnostic tool for lymphatic diseases. While this technique offers numerous advantages, the kinetics of ICG at the injection site can pose challenges for a detailed diagnosis. In this study, we synthesized various ICG derivatives possessing cationic, anionic, or uncharged substituents and examined their photochemical properties, binding affinity to human serum albumin, as well as their correlation to pharmacokinetics in mice. The introduction of different substituents not only affected certain physiochemical properties, but also impacted the pharmacokinetics within the lymph nodes. Immunofluorescence imaging suggested that the extent of uptake of the ICG derivatives by phagocytic cells may affect the retention of the contrast ratios in the lymph nodes. These findings can provide new insights in the pharmacokinetics in lymphatic tissues, which could be useful for the development of novel fluorescent agents for lymph imaging.

Targeting of 3D oral cancer spheroids by αVß6 integrin using near-infrared peptide-conjugated IRDye 680.

BACKGROUND: In the treatment of oral cavity cancer, margin status is one of the most critical prognostic factors. Positive margins are associated with higher local recurrence and lower survival rates. Therefore, the universal goal of oral surgical oncology is to achieve microscopically clear margins. Near-infrared fluorescence guided surgery (FGS) could improve surgical resection using fluorescent probes. αVß6 integrin has shown great potential for cancer targeting due to its overexpression in oral cancers. Red fluorescent contrast agent IRDye 680 coupled with anti-αVß6 peptide (IRDye-A20) represents an asset to improve FGS of oral cancer. This study investigates the potential of IRDye-A20 as a selective imaging agent in 3D three-dimensional tongue cancer cells. METHODS: αVß6 integrin expression was evaluated by RT-qPCR and Western Blotting in 2D HSC-3 human tongue cancer cells and MRC-5 human fibroblasts. Targeting ability of IRDye-A20 was studied in both cell lines by flow cytometry technique. 3D tumor spheroid models, homotypic (HSC-3) and stroma-enriched heterotypic (HSC-3/MRC-5) spheroids were produced by liquid overlay procedure and further characterized using (immuno)histological and fluorescence-based techniques. IRDye-A20 selectivity was evaluated in each type of spheroids and each cell population. RESULTS: αVß6 integrin was overexpressed in 2D HSC-3 cancer cells but not in MRC-5 fibroblasts and consistently, only HSC-3 were labelled with IRDye-A20. Round shaped spheroids with an average diameter of 400 µm were produced with a final ratio of 55%/45% between HSC-3 and MRC-5 cells, respectively. Immunofluorescence experiments demonstrated an uniform expression of αVß6 integrin in homotypic spheroid, while its expression was restricted to cancer cells only in heterotypic spheroid. In stroma-enriched 3D model, Cytokeratin 19 and E-cadherin were expressed only by cancer cells while vimentin and fibronectin were expressed by fibroblasts. Using flow cytometry, we demonstrated that IRDye-A20 labeled the whole homotypic spheroid, while in the heterotypic model all cancer cells were highly fluorescent, with a negligible fluorescence in fibroblasts. CONCLUSIONS: The present study demonstrated an efficient selective targeting of A20FMDV2-conjugated IRDye 680 in 3D tongue cancer cells stroma-enriched spheroids. Thus, IRDye-A20 could be a promising candidate for the future development of the fluorescence-guided surgery of oral cancers.

Polypeptide nanoparticles conjugated with an NIR-II organic dye for TRPV1 channel blockade enhance mild phototheranostics.

Photothermal therapy (PTT) has attracted attention as a highly effective non-invasive treatment method. However, the high localized temperatures (>50 °C) required for its treatment will inevitably cause damage to the surrounding normal tissues. Therefore, it is important to develop novel and effective strategies to achieve mild photothermal therapy (mPTT). The overexpression of heat shock proteins (HSPs), a widespread heat stress protein, leads to the generation of heat resistance in cancer cells, which seriously affects the therapeutic effect. Thus, inhibiting the expression of HSPs to reduce the heat resistance of tumor cells is expected to enhance the therapeutic effect of mPTT. Here, we successfully synthesized a fluorescent probe bonded with an amphiphilic polypeptide to a cyanine dye and achieved physical encapsulation of the blocker SB705498 through a self-assembly process. SB705498 promotes transient receptor potential vanilloid member 1 (TRPV1) channel blockade that can inhibit the translocation of the heat shock transcription factor 1 (HSF 1) by blocking the influx of calcium and thus affecting the expression of HSPs, which has the potential to enhance the thermotherapy of cancer under mild conditions. In addition, the nanoparticles enabled NIR-II fluorescence imaging with good stability and high photothermal conversion efficiency (48.10 %). Therefore, this study provides a new strategy for realizing precise mPTT(<45 °C) guided by NIR-II imaging. STATEMENT OF SIGNIFICANCE: Inhibition of overexpression of heat shock proteins (HSPs) in cancer photothermal therapy (PTT) is expected to enhance the therapeutic effect of mild photothermal therapy (mPTT). In this study, we synthesized a fluorescent probe bonded to cyanine dyes with amphiphilic polypeptides and physically wrapped the blocker SB705498 through a self-assembly process. As a transient receptor potential vanillin 1 (TRPV1) channel blocker, SB705498 inhibits heat shock transcription factor 1 (HSF1) translocation by blocking calcium ion influx, thereby improving mPTT efficacy by inhibiting the expression of HSPs. The nanoparticles also enable NIR-II fluorescence imaging with good stability and high photothermal conversion efficiency (48.10 %). Thus, this study provides a new strategy for NIR-II mPTT.

Visualizing alpha-synuclein and iron deposition in M83 mouse model of Parkinson's disease in vivo.

Abnormal alpha-synuclein (αSyn) and iron accumulation in the brain play an important role in Parkinson's disease (PD). Herein, we aim to visualize αSyn inclusions and iron deposition in the brains of M83 (A53T) mouse models of PD in vivo. The fluorescent pyrimidoindole derivative THK-565 probe was characterized by means of recombinant fibrils and brains from 10- to 11-month-old M83 mice. Concurrent wide-field fluorescence and volumetric multispectral optoacoustic tomography (vMSOT) imaging were subsequently performed in vivo. Structural and susceptibility weighted imaging (SWI) magnetic resonance imaging (MRI) at 9.4 T as well as scanning transmission x-ray microscopy (STXM) were performed to characterize the iron deposits in the perfused brains. Immunofluorescence and Prussian blue staining were further performed on brain slices to validate the detection of αSyn inclusions and iron deposition. THK-565 showed increased fluorescence upon binding to recombinant αSyn fibrils and αSyn inclusions in post-mortem brain slices from patients with PD and M83 mice. Administration of THK-565 in M83 mice showed higher cerebral retention at 20 and 40 min post-intravenous injection by wide-field fluorescence compared to nontransgenic littermate mice, in congruence with the vMSOT findings. SWI/phase images and Prussian blue indicated the accumulation of iron deposits in the brains of M83 mice, presumably in the Fe3+ form, as evinced by the STXM results. In conclusion, we demonstrated in vivo mapping of αSyn by means of noninvasive epifluorescence and vMSOT imaging and validated the results by targeting the THK-565 label and SWI/STXM identification of iron deposits in M83 mouse brains ex vivo.

A novel AIE fluorescent probe for the detection and imaging of hydrogen peroxide in living tumor cells and in vivo.

Hydrogen peroxide (H2O2), a key reactive oxygen species (ROS), plays crucial roles in redox signaling pathways and immune responses associated with cell proliferation, differentiation, migration, and disease progression. The selective monitoring of overproduced H2O2 is important for understanding the diagnosis and pathogenesis of diseases such as cardiovascular disease, cancers, diabetes, Parkinson's disease, Alzheimer's disease, and inflammation. In this paper, an AIE fluorescent probe BQM-H2O2 was developed by connecting phenyl borate with the fluorophore BQM-PNH for selective detection of H2O2. In the presence of H2O2 at fw = 99% (pH = 7.4, 1% DMSO), the probe BQM-H2O2 could generate strong fluorescent signals due to the oxidation of the borate ester. The probe exhibited high selectivity and a low detection limit toward H2O2 with the calculated LOD of 112.6 nM. Importantly, it was employed in the detection of exogenous and endogenous hydrogen peroxide in 4T1 cells with low cytotoxicity. This probe has also been successfully applied to imaging of H2O2 in Blab/c mice bearing 4T1 graft tumors.

Near-infrared fluorescence imaging technology guided margin design in oral squamous cell carcinoma: a single-centre retrospective study.

Objective: The margin status of oral squamous cell carcinoma patients is considered to be predictive of recurrence and long-term survival. Therefore, precise intraoperative margin assessment is crucial. This study investigated the feasibility of using near-infrared fluorescence imaging technology to guide margin design in oral squamous cell carcinoma patients. Methods: In this retrospective study, indocyanine green solution was intravenously injected preoperatively into patients. Intraoperatively, the surgical area was illuminated using a near-infrared fluorescence imaging system, which caused the lesion to fluoresce in the surgical area. Surgery was performed with the assistance of fluorescence imaging. The fluorescence intensity of the lesion area and surrounding normal tissue was recorded during surgery. Intraoperative margins were sent for rapid pathology, and postoperative margin pathology results were documented. Results: Sixteen patients were included in this study (7 males, 9 females), with an average age of 65.65 ± 12.37 years. Preoperative biopsy and postoperative pathology confirmed oral squamous cell carcinoma in all patients. No cancer cells were found in the margin pathology results. The average fluorescence intensity of the lesion area was 214 ± 4.70, and that of the surrounding normal tissue was 104.63 ± 3.14. There was no significant difference in the fluorescence intensity values of the lesion areas among all patients (F=0.38, P>0.05). There was a significant difference in fluorescence intensity between the lesion area and surrounding normal tissue (t=33.76, P<0.05). Conclusion: Near-infrared fluorescence imaging technology can aid in real-time imaging differentiation of lesion areas based on differences in fluorescence intensity during surgery. The use of this technology can assist surgeons in assessing the safety margin and reliably guide surgery.

TMVP1448, a novel peptide improves detection of primary tumors and metastases by specifically targeting VEGFR-3.

Lymphangiogenesis at primary tumor and draining lymph nodes plays a pivotal role in tumor metastasis, which has been demonstrated to be regulated by the vascular endothelial growth factor receptor 3 (VEGFR-3) pathway. However, the effect of molecular imaging peptides, which specifically bind VEGFR-3, in tracing tumors remains unclear. We prepared a novel peptide, TMVP1448, with high-affinity to VEGFR-3. The dissociation constant (KD) of TMVP1448 with VEGFR-3 was 7.07 ×10-7 M. In vitro cellular assay showed that TMVP1448 could bind specifically with VEGFR-3. Near infrared imaging results showed that Cy7-TMVP1448 was able to accurately trace primary and metastatic cancers, and PET/CT results showed that [68Ga]Ga-DOTA-TMVP1448 was superior to commonly used radiotracers 18F-FDG. Additionally, no significant negative effect of TMVP1448 was found in mice. Our results suggested that TMVP1448 had great potential for future clinical applications in fluorescence imaging and nuclear imaging of tumors.

The delayed kinetics of Myddosome formation explains why amyloid-beta aggregates trigger Toll-like receptor 4 less efficiently than lipopolysaccharide.

The Myddosome is a key innate immune signalling platform. It forms at the cell surface and contains MyD88 and IRAK proteins which ultimately coordinate the production of pro-inflammatory cytokines. Toll-like receptor 4 (TLR4) signals via the Myddosome when triggered by lipopolysaccharide (LPS) or amyloid-beta (Aß) aggregates but the magnitude and time duration of the response are very different for reasons that are unclear. Here, we followed the formation of Myddosomes in live macrophages using local delivery of TLR4 agonist to the cell surface and visualisation with 3D rapid light sheet imaging. This was complemented by super-resolution imaging of Myddosomes in fixed macrophages to determine the size of the signalling complex at different times after triggering. Myddosomes formed more rapidly after LPS than in response to sonicated Aß 1-42 fibrils (80 vs 372 s). The mean lifetimes of the Myddosomes were also shorter when triggered by LPS compared to sonicated Aß fibrils (170 and 220 s), respectively. In both cases, a range of Myddosome of different sizes (50-500 nm) were formed. In particular, small round Myddosomes around 100 nm in size formed at early time points, then reduced in proportion over time. Collectively, our data suggest that compared to LPS the multivalency of Aß fibrils leads to the formation of larger Myddosomes which form more slowly and, due to their size, take longer to disassemble. This explains why sonicated Aß fibrils results in less efficient triggering of TLR4 signalling and may be a general property of protein aggregates.

Impact of Indocyanine Green Angiography on Postoperative Parathyroid Function: A Propensity Score Matching Study.

Background: Thyroidectomy constitutes an important portion of endocrine surgery procedures and is associated with various complications such as bleeding, recurrent laryngeal nerve injury, and postoperative hypoparathyroidsm. Effective parathyroid preservation during thyroid surgery is crucial for patient well-being, with current strategies heavily reliant on surgeon experience. Among various methods, Indocyanine Green Angiography (ICGA) offers a promising method for intraoperative assessment of parathyroid gland perfusion. Methods: In a retrospective study, patients undergoing bilateral thyroidectomy from January 2021 to January 2023 were analyzed, excluding those with previous thyroidectomy, parathyroid disease, or chronic kidney disease. The study compared a control group (n = 175) with an ICGA group (n = 120), using propensity score matching for statistical analysis. Matched cohorts included 120 patients in each group. The primary outcome of this study was identified as temporary postoperative hypoparathyroidism, with secondary outcomes including the rate of parathyroid reimplantation and the incidence of permanent postoperative hypoparathyroidism. Results: The ICGA group showed significantly more parathyroid autotransplantations (p < 0.01). While not statistically significant, the control group had a higher incidence of temporary postoperative hypoparathyroidism (p < 0.09). Rates of hypocalcemia on postoperative day 1 and permanent hypocalcemia were similar. Subgroup analysis indicated more postoperative day 1 hypoparathyroidism in the control group during central neck dissections (p < 0.049). Conclusions: Intraoperative ICGA use correlated with higher parathyroid autotransplantation and suggested reduced postoperative hypoparathyroidism. Changes in fluorescence intensity following a second ICG injection may provide an objective method to assess parathyroid perfusion. Further large-scale studies are needed to fully understand ICGA's impact on parathyroid preservation.