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Significance: ALA-PpIX and second-window indocyanine green (ICG) have been studied widely for guiding the resection of high-grade gliomas. These agents have different mechanisms of action and uptake characteristics, which can affect their performance as surgical guidance agents. Elucidating these differences in animal models that approach the size and anatomy of the human brain would help guide the use of these agents. Herein, we report on the use of a new pig glioma model and fluorescence cryotomography to evaluate the 3D distributions of both agents throughout the whole brain. Aim: We aim to assess and compare the 3D spatial distributions of ALA-PpIX and second-window ICG in a glioma-bearing pig brain using fluorescence cryotomography. Approach: A glioma was induced in the brain of a transgenic Oncopig via adeno-associated virus delivery of Cre-recombinase plasmids. After tumor induction, the pro-drug 5-ALA and ICG were administered to the animal 3 and 24 h prior to brain harvest, respectively. The harvested brain was imaged using fluorescence cryotomography. The fluorescence distributions of both agents were evaluated in 3D in the whole brain using various spatial distribution and contrast performance metrics. Results: Significant differences in the spatial distributions of both agents were observed. Indocyanine green accumulated within the tumor core, whereas ALA-PpIX appeared more toward the tumor periphery. Both ALA-PpIX and second-window ICG provided elevated tumor-to-background contrast (13 and 23, respectively). Conclusions: This study is the first to demonstrate the use of a new glioma model and large-specimen fluorescence cryotomography to evaluate and compare imaging agent distribution at high resolution in 3D.
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Neoplasias Encefálicas , Glioma , Imagenología Tridimensional , Verde de Indocianina , Animales , Verde de Indocianina/farmacocinética , Verde de Indocianina/química , Porcinos , Neoplasias Encefálicas/diagnóstico por imagen , Glioma/diagnóstico por imagen , Glioma/patología , Imagenología Tridimensional/métodos , Ácido Aminolevulínico/farmacocinética , Encéfalo/diagnóstico por imagen , Imagen Óptica/métodos , Modelos Animales de EnfermedadRESUMEN
Significance: The arterial input function (AIF) plays a crucial role in correcting the time-dependent concentration of the contrast agent within the arterial system, accounting for variations in agent injection parameters (speed, timing, etc.) across patients. Understanding the significance of the AIF can enhance the accuracy of tissue vascular perfusion assessment through indocyanine green-based dynamic contrast-enhanced fluorescence imaging (DCE-FI). Aim: We evaluate the impact of the AIF on perfusion assessment through DCE-FI. Approach: A total of 144 AIFs were acquired from 110 patients using a pulse dye densitometer. Simulation and patient intraoperative imaging were conducted to validate the significance of AIF for perfusion assessment based on kinetic parameters extracted from fluorescence images before and after AIF correction. The kinetic model accuracy was evaluated by assessing the variability of kinetic parameters using individual AIF versus population-based AIF. Results: Individual AIF can reduce the variability in kinetic parameters, and population-based AIF can potentially replace individual AIF for estimating wash-out rate ( k ep ), maximum intensity ( I max ), ingress slope with lower differences compared with those in estimating blood flow, volume transfer constant ( K trans ), and time to peak. Conclusions: Individual AIF can provide the most accurate perfusion assessment compared with assessment without AIF or based on population-based AIF correction.
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Verde de Indocianina , Imagen Óptica , Humanos , Imagen Óptica/métodos , Verde de Indocianina/química , Verde de Indocianina/farmacocinética , Femenino , Persona de Mediana Edad , Anciano , Masculino , Medios de Contraste/química , Adulto , Arterias/diagnóstico por imagen , Imagen de Perfusión/métodos , Simulación por ComputadorRESUMEN
INTRODUCTION: To date, radical surgery remains the best curative option in patients with early-stage lung cancer. In patients with small lung lesions, video-assisted thoracic surgery (VATS) should be increasingly chosen as a fundamental alternative to thoracotomy as it is associated with less postoperative pain and better quality of life. This scenario necessarily increases the need for thoracic surgeons to implement new localization techniques. The conventional near-infrared (NIR) indocyanine green (ICG) method demonstrated a significant limitation in deep cancer recognition, principally due to its intrinsic low-depth tissue penetration. Similarly, the lymph-node sentinel approach conducted by the ICG method was demonstrated to be inefficient, mainly due to the non-specificity of the tracker and the irregular pathway of pulmonary lymph node drainage. Our study aims to evaluate the effectiveness of Cetuximab- IRDye800CW in marking lung nodules and mediastinal lymph nodes. METHODS AND ANALYSIS: This study is defined as an open-label, single-arm, single-stage phase II trial evaluating the effectiveness of Cetuximab-IRDye800CW in detecting tumors and lymph-node metastases in patients with lung cancer who are undergoing video-assisted thoracic surgery (VATS). Cetuximab is a monoclonal antibody that binds, inhibits, and degrade the EGFR. The IRDye® 800CW, an indocyanine-type NIR fluorophore, demonstrated enhanced tissue penetration compared to other NIR dyes. The combination with the clinical approved monoclonal antibody anti-epidermal growth factor EGFR Cetuximab (Cetuximab-IRDye800) has shown promising results as a specific tracker in different cancer types (i.e., brain, pancreas, head, and neck). The study's primary outcome is focused on the proportion of patients with lung nodules detected during surgery using an NIR camera. The secondary outcomes include a broad spectrum of items, including the proportion of patients with detection of unexpected cancer localization during surgery by NIR camera and the proportion of patients with negative surgical margins, the evaluation of the time spawns between the insertion of the NIR camera and the visualization of the nodule and the possible morbidity of the drug assessed during and after the drug infusion. ETHICS AND DISSEMINATION: This trial has been approved by the Ethical Committee of Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino (Torino, Italy) and by the Italian Medicines Agency (AIFA). Findings will be written as methodology papers for conference presentations and published in peer-reviewed journals. The Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino, the University of Torino, and the AIRC Public Engagement Divisions will help identify how best to publicize the findings.Trial registration EudraCT 202,100,645,430. CLINICALTRIALS: gov NCT06101394 (October 23, 2023).
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Neoplasias Pulmonares , Imagen Molecular , Cirugía Torácica Asistida por Video , Humanos , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/diagnóstico por imagen , Cirugía Torácica Asistida por Video/métodos , Imagen Molecular/métodos , Espectroscopía Infrarroja Corta/métodos , Cetuximab/uso terapéutico , Cetuximab/administración & dosificación , Verde de Indocianina/administración & dosificación , Metástasis Linfática , Femenino , Masculino , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Ganglios Linfáticos/patología , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/cirugíaRESUMEN
Accurate lymph node (LN) retrieval during colorectal carcinoma resection is pivotal for precise N-staging and the determination of adjuvant therapy. Current guidelines recommend the examination of at least 12 mesocolic or mesorectal lymph nodes for accurate staging. Traditional histological processing techniques, reliant on visual inspection and palpation, are time-consuming and heavily dependent on the examiner's expertise and availability. Various methods have been documented to enhance LN retrieval from colorectal specimens, including intra-arterial ex vivo methylene blue injection. Recent studies have explored the utility of indocyanine green (ICG) fluorescence imaging for visualizing pericolic lymph nodes and identifying sentinel lymph nodes in colorectal malignancies. This study included 10 patients who underwent colon resection for malignant tumors. During surgery, intravenous ICG dye and an endoscopic camera were employed to assess intestinal perfusion. Post-resection, ex vivo intra-arterial administration of ICG dye was performed on the specimens, followed by routine histological processing and an ICG-assisted lymph node dissection. The objective was to evaluate whether ICG imaging could identify additional lymph nodes compared to routine manual dissection and to assess the clinical relevance of these findings. For each patient, a minimum of 12 lymph nodes (median = 25.5, interquartile range = 12.25, maximum = 33) were examined. ICG imaging facilitated the detection of a median of three additional lymph nodes not identified during routine processing. Metastatic lymph nodes were found in four patients however no additional metastatic nodes were detected with ICG assistance. Our findings suggest that ex vivo intra-arterial administration of indocyanine green dye can augment lymph node dissection, particularly in cases where the number of lymph nodes retrieved is below the recommended threshold of 12.
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Neoplasias Colorrectales , Estudios de Factibilidad , Verde de Indocianina , Escisión del Ganglio Linfático , Ganglios Linfáticos , Humanos , Verde de Indocianina/administración & dosificación , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/diagnóstico por imagen , Neoplasias Colorrectales/cirugía , Proyectos Piloto , Femenino , Masculino , Anciano , Ganglios Linfáticos/patología , Ganglios Linfáticos/diagnóstico por imagen , Persona de Mediana Edad , Escisión del Ganglio Linfático/métodos , Metástasis Linfática/patología , Metástasis Linfática/diagnóstico por imagen , Colorantes , Fluorescencia , Imagen Óptica/métodos , Anciano de 80 o más Años , Colorantes Fluorescentes/administración & dosificaciónRESUMEN
Purpose: We evaluated the features predicting visual acuity (VA) after one year in neovascular age-related macular degeneration (nAMD) patients. Methods: A total of 527 eyes of 506 patients were included. Machine learning (ML) models were trained to predict VA deterioration beyond a logarithm of the minimum angle of resolution of 1.0 after 1 year based on the sequential addition of multimodal data. BaseM models used clinical data (age, sex, treatment regimen, and VA), SegM models included fluid volumes from optical coherence tomography (OCT) images, and RawM models used probabilities of visual deterioration (hereafter probability) from deep learning classifiers trained on baseline OCT (OCT0) and OCT after three loading doses (OCT3), fluorescein angiography, and indocyanine green angiography. We applied SHapley Additive exPlanations (SHAP) for machine learning model interpretation. Results: The RawM model based on the probability of OCT0 outperformed the SegM model (area under the receiver operating characteristic curve of 0.95 vs. 0.91). Adding probabilities from OCT3, fluorescein angiography, and indocyanine green angiography to RawM showed minimal performance improvement, highlighting the practicality of using raw OCT0 data for predicting visual outcomes. Applied SHapley Additive exPlanations analysis identified VA after 3 months and OCT3 probability values as the most influential features over quantified fluid segments. Conclusions: Integrating multimodal data to create a visual predictive model yielded accurate, interpretable predictions. This approach allowed the identification of crucial factors for predicting VA in patients with nAMD. Translational Relevance: Interpreting a predictive model for 1-year VA in patients with nAMD from multimodal data allowed us to identify crucial factors for predicting VA.
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Angiografía con Fluoresceína , Aprendizaje Automático , Tomografía de Coherencia Óptica , Agudeza Visual , Humanos , Agudeza Visual/fisiología , Femenino , Masculino , Anciano , Tomografía de Coherencia Óptica/métodos , Angiografía con Fluoresceína/métodos , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/uso terapéutico , Inhibidores de la Angiogénesis/administración & dosificación , Degeneración Macular Húmeda/tratamiento farmacológico , Degeneración Macular Húmeda/fisiopatología , Degeneración Macular Húmeda/diagnóstico por imagen , Degeneración Macular Húmeda/diagnóstico , Verde de Indocianina/administración & dosificación , Inyecciones Intravítreas , Curva ROC , Estudios Retrospectivos , Ranibizumab/uso terapéutico , Ranibizumab/administración & dosificación , Persona de Mediana EdadRESUMEN
BACKGROUND: Pancreaticoduodenectomy is associated with an incidence of postoperative complications of approximately 41%. One of the most severe complications is a postoperative pancreatic fistula. The exact cause of postoperative fistula development is still unknown, but it appears to be multifactorial. Proper perfusion of pancreatic remnant is essential for the healing of pancreaticojejunostomy. To date, there is no method to reliably evaluate the vascular supply of the remnant. One of the methods for the assessment of organ perfusion is the indocyanine green fluorescence. This study aims to determine if indocyanine green fluorescence is a reliable method to measure the perfusion of the post-resection pancreatic remnant. The secondary outcome is to determine if intraoperative evaluation of the vascular supply of the post-resection remnant may predict the increased risk of postoperative pancreatic fistula development. METHODS: This study is designed as a prospective, observational study. All consecutive patients undergoing open or robotic pancreaticoduodenectomies at our department during the 1st May 2024-31st December 2026 period will be enrolled. The exclusion criteria are an allergy to indocyanine green and refusal by the patient. The adequacy of the vascular supply of the post-resection pancreatic remnant will be intraoperatively evaluated using a fluorescence detector. Patients will be divided into two groups: Those with high risk of pancreatic fistula development and those with low risk. The incidence of pancreatic fistulas in both groups is to be compared. Postoperative data including morbidity, mortality, hospital stay, intensive care unit stay and postoperative fistula development will be collected. DISCUSSION: If an intraoperative assessment of the perfusion of post-resection pancreatic remnant using indocyanine green is proven to be a suitable method to estimate the increased risk of the pancreatic fistula, the list of the existing known risk factors could be expanded. In the most high-risk patients the modification of the surgical procedure could be considered. TRIAL REGISTRATION: Number: NCT06198400 ClinicalTrials.Gov. Date 08.01.2024.
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Verde de Indocianina , Fístula Pancreática , Pancreaticoduodenectomía , Complicaciones Posoperatorias , Humanos , Pancreaticoduodenectomía/efectos adversos , Pancreaticoduodenectomía/métodos , Estudios Prospectivos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/diagnóstico , Fístula Pancreática/etiología , Fístula Pancreática/epidemiología , Páncreas/irrigación sanguínea , Páncreas/cirugía , Masculino , Femenino , FluorescenciaRESUMEN
BACKGROUND: T cell-based immunotherapies are facing great challenges in the recruitment and activation of tumor-specific T cells against solid tumors. Among which, utilizing nanobody (Nb) or nanobodies (Nbs) to construct T cell engager has emerged as a more practical potential for enhancing the anti-tumor effectiveness of T cells. Here, we designed a new Nb-guided multifunctional T cell engager (Nb-MuTE) that not only recruited effector T cells into the tumor tissues, but also efficiently activated T cells anti-tumor immunity when synergies with photothermal effect. RESULTS: The Nb-MuTE, which was constructed based on an indocyanine green (ICG)-containing liposome with surface conjugation of CD105 and CD3 Nbs, and showed excellent targetability to both tumor and T cells, following enhancement of activation, proliferation and cytokine secretion of tumor-specific T cells. Notably, the immunological anti-tumor functions of Nb-MuTE-mediated T cells were further enhanced by the ICG-induced photothermal effect in vitro and in vivo. CONCLUSIONS: Such a new platform Nb-MuTE provides a practical and "all-in-one" strategy to potentiate T cell responses for the treatment of solid tumor in clinic.
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Inmunoterapia , Verde de Indocianina , Anticuerpos de Dominio Único , Linfocitos T , Animales , Anticuerpos de Dominio Único/química , Anticuerpos de Dominio Único/inmunología , Ratones , Linfocitos T/inmunología , Verde de Indocianina/química , Inmunoterapia/métodos , Línea Celular Tumoral , Humanos , Neoplasias/terapia , Neoplasias/inmunología , Femenino , Ratones Endogámicos BALB C , Terapia Fototérmica/métodos , Liposomas/química , Activación de Linfocitos , Ratones Endogámicos C57BL , Complejo CD3/inmunologíaRESUMEN
Phototherapy is a promising antitumor modality, which consists of photothermal therapy (PTT) and photodynamic therapy (PDT). However, the efficacy of phototherapy is dramatically hampered by local hypoxia in tumors, overexpression of indoleamine 2,3-dioxygenase (IDO) and programmed cell death ligand-1 (PD-L1) on tumor cells. To address these issues, self-assembled multifunctional polymeric micelles (RIMNA) were developed to co-deliver photosensitizer indocyanine green (ICG), oxygenator MnO2, IDO inhibitor NLG919, and toll-like receptor 4 agonist monophosphoryl lipid A (MPLA). It is worth noting that RIMNA polymeric micelles had good stability, uniform morphology, superior biocompatibility, and intensified PTT/PDT effect. What's more, RIMNA-mediated IDO inhibition combined with programmed death receptor-1 (PD-1)/PD-L1 blockade considerably improved immunosuppression and promoted immune activation. RIMNA-based photoimmunotherapy synergized with PD-1 antibody could remarkably inhibit primary tumor proliferation, as well as stimulate the immunity to greatly suppress lung metastasis and distant tumor growth. This study offers an efficient method to reinforce the efficacy of phototherapy and alleviate immunosuppression, thereby bringing clinical benefits to cancer treatment.
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Neoplasias del Colon , Inmunoterapia , Micelas , Fototerapia , Polímeros , Receptor de Muerte Celular Programada 1 , Animales , Neoplasias del Colon/terapia , Neoplasias del Colon/inmunología , Neoplasias del Colon/tratamiento farmacológico , Ratones , Inmunoterapia/métodos , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Polímeros/química , Línea Celular Tumoral , Fototerapia/métodos , Verde de Indocianina/química , Verde de Indocianina/uso terapéutico , Verde de Indocianina/farmacología , Ratones Endogámicos BALB C , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Fotoquimioterapia/métodos , Femenino , Humanos , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/metabolismo , Lípido A/análogos & derivadosRESUMEN
INTRODUCTION: Robotic-assisted surgery has become increasingly popular because of its potential benefits. Anatomical liver resection (ALR) is a valuable strategy in hepatocellular carcinoma (HCC) management. ALR with indocyanine green (ICG) fluorescence navigation was reported as an effective solution for segment identification. We reported a simple and convenient "preoperative positive staining technique" for laparoscopic ALR to overcome some limitations. To our knowledge, this is the first report of robotic-assisted surgery in which ALR was performed using this technique. MATERIALS AND SURGICAL TECHNIQUE: A 69-year-old man presented with a 12-mm HCC in segment 8. Preoperative three-dimensional simulation images showed that the fourth-order branch of the portal vein was a tumor-bearing portal pedicle. After anesthesia induction, 1 mL of 0.025 mg/mL ICG was injected percutaneously into this branch under B-mode ultrasound guidance before pneumoperitoneum. A robotic laparoscope was inserted. The preoperative positive staining area was clearly stained on the liver surface with the Firefly mode on the da Vinci Xi system. Based on the demarcation line, the liver parenchymal resection was started. The ICG fluorescence staining area was checked frequently on the resected side of the liver transection plane. Subsequently, the fourth-order portal branch was identified with the ICG fluorescence technique and ligated. Finally, the specimen was resected. The operation took 352 min, with 10 mL of blood loss, and was completed without any operative problems. DISCUSSION: Although many cases are required, the proposed preoperative positive staining technique appears useful for accurate and precise surgery given the increasing application of robotic-assisted hepatectomy.
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Carcinoma Hepatocelular , Hepatectomía , Verde de Indocianina , Neoplasias Hepáticas , Procedimientos Quirúrgicos Robotizados , Humanos , Anciano , Masculino , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Procedimientos Quirúrgicos Robotizados/métodos , Hepatectomía/métodos , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/patología , Ultrasonografía Intervencional , Colorantes , Laparoscopía/métodos , Cuidados Preoperatorios/métodosRESUMEN
Breast cancer therapy has significantly advanced by targeting the programmed cell death-ligand 1/programmed cell death-1 (PD-L1/PD-1) pathway. BMS-202 (a smallmolecule PD-L1 inhibitor) induces PD-L1 dimerization to block PD-1/PD-L1 interactions, allowing the T-cell-mediated immune response to kill tumor cells. However, immunotherapy alone has limited effects. Clinically approved photodynamic therapy (PDT) activates immunity and selectively targets malignant cells. However, PDT aggravates hypoxia, which may compromise its therapeutic efficacy and promote tumor metastasis. We designed a tumor-specific delivery nanoplatform of liposomes that encapsulate the hypoxia-sensitive antitumor drug tirapazamine (TPZ) and the small-molecule immunosuppressant BMS. New indocyanine green (IR820)-loaded polyethylenimine-folic acid (PEI-FA) was complexed with TPZ and BMS-loaded liposomes via electrostatic interactions to form lipid nanocomposites. This nanoplatform can be triggered by near-infrared irradiation to induce PDT, resulting in a hypoxic tumor environment and activation of the prodrug TPZ to achieve efficient chemotherapy. The in vitro and in vivo studies demonstrated excellent combined PDT, chemotherapy, and immunotherapy effects on the regression of distant tumors and lung metastases, providing a reference method for the preparation of targeted agents for treating breast cancer.
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Neoplasias de la Mama , Inmunoterapia , Liposomas , Liposomas/química , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/terapia , Inmunoterapia/métodos , Animales , Ratones , Humanos , Línea Celular Tumoral , Fotoquimioterapia/métodos , Verde de Indocianina/química , Verde de Indocianina/uso terapéutico , Verde de Indocianina/análogos & derivados , Ratones Endogámicos BALB C , Tirapazamina/química , Tirapazamina/farmacología , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Fototerapia/métodosRESUMEN
As a novel therapeutic approach, photothermal therapy (PTT) combined with chemotherapy can synergistically produce antitumor effects. Herein, dithiodipropionic acid (DTDP) was used as a donor of disulfide bonds sensitive to the tumor microenvironment for establishing chemical bonding between the photosensitizer indocyanine green amino (ICG-NH2) and acidified single-walled carbon nanotubes (CNTs). The CNT surface was then coated with conjugates (HD) formed by the targeted modifier hyaluronic acid (HA) and 1,2-tetragacylphosphatidyl ethanolamine (DMPE). After doxorubicin hydrochloride (DOX), used as the model drug, was loaded by CNT carriers, functional nano-delivery systems (HD/CNTs-SS-ICG@DOX) were developed. Nanosystems can effectively induce tumor cell (MCF-7) death in vitro by accelerating cell apoptosis, affecting cell cycle distribution and reactive oxygen species (ROS) production. The in vivo antitumor activity results in tumor-bearing model mice, further verifying that HD/CNTs-SS-ICG@DOX inhibited tumor growth most significantly by mediating a synergistic effect between chemotherapy and PTT, while various functional nanosystems have shown good biological tissue safety. In conclusion, the composite CNT delivery systems developed in this study possess the features of high biocompatibility, targeted delivery, and responsive drug release, and can achieve the efficient coordination of chemotherapy and PTT, with broad application prospects in cancer treatment.
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Doxorrubicina , Nanotubos de Carbono , Terapia Fototérmica , Microambiente Tumoral , Nanotubos de Carbono/química , Animales , Humanos , Microambiente Tumoral/efectos de los fármacos , Terapia Fototérmica/métodos , Ratones , Doxorrubicina/farmacología , Doxorrubicina/química , Doxorrubicina/administración & dosificación , Doxorrubicina/uso terapéutico , Verde de Indocianina/química , Células MCF-7 , Especies Reactivas de Oxígeno/metabolismo , Apoptosis/efectos de los fármacos , Sistemas de Liberación de Medicamentos/métodos , Femenino , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Ensayos Antitumor por Modelo de Xenoinjerto , Ratones Endogámicos BALB C , Terapia Combinada/métodos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Antineoplásicos/administración & dosificación , Ácido Hialurónico/químicaRESUMEN
BACKGROUND: Breast cancer is a global health problem, and sentinel lymph node biopsy (SLNB) is the standard procedure for early-stage breast cancer. Technetium-99 (TC-99), alone or combined with blue dye (BD) are conventional tracers for SLNB, but they have safety, availability, and cost limitations. Indocyanine green (ICG) is an alternative tracer that has been gaining acceptance among healthcare professionals. This study aimed at assessing the clinical and economic value of ICG in hospital settings, using the health technology assessment (HTA) framework. METHODS: We conducted a comprehensive evaluation of ICG for SLNB, based on literature sources and data collected from two Italian hospitals that switched from TC-99 to ICG. We analyzed ICG's technical attributes through technology documentation and relevant databases. We performed a systematic literature review of 36 studies to assess the clinical effectiveness and safety of ICG. We obtained organizational insights from clinicians and the clinical engineer involved in the study. We applied Time-Driven Activity-Based Costing (TDABC) and Budget Impact Analysis (BIA) to estimate the economic impact of ICG. The ethical, legal, and social implications of ICG were considered through clinicians' inputs and technology documentation. RESULTS: Our results showed that ICG had equivalent or superior clinical effectiveness compared to TC-99 and BD, with minimal adverse events. ICG simplified the surgical pathways, by streamlining procedures, reducing waiting times, and increasing flexibility in scheduling surgeries. Moreover, the TDABC analysis showed significant cost reductions by avoiding the need for pre-operative lymphoscintigraphy and hospitalization, with average savings per single care pathway of around 18% for ICG compared to TC-99. Finally, ICG improved patient experience, and proved regulatory compliance. CONCLUSIONS: This study provided strong evidence for ICG's clinical and economic value for SLNB in breast cancer. It ascertained ICG as a valuable alternative to conventional tracers, ensuring clinical effectiveness along with economic and organizational benefits.
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Neoplasias de la Mama , Verde de Indocianina , Biopsia del Ganglio Linfático Centinela , Humanos , Neoplasias de la Mama/patología , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/economía , Femenino , Biopsia del Ganglio Linfático Centinela/métodos , Biopsia del Ganglio Linfático Centinela/economía , Análisis Costo-Beneficio , Tecnecio , ColorantesRESUMEN
Gene transfection, defined by the delivery of nucleic acids into cellular compartments, stands as a crucial procedure in gene therapy. While branched polyethylenimine (PEI) is widely regarded as the "gold standard" for nonviral vectors, its cationic nature presents several issues, including nonspecific protein adsorption and notable cytotoxicity. Additionally, it often fails to achieve high transfection efficiency, particularly with hard-to-transfect cell types. To overcome these challenges associated with PEI as a vector for plasmid DNA (pDNA), the photothermal agent indocyanine green (ICG) is integrated with PEI and pDNA to form the PEI/ICG/pDNA (PI/pDNA) complex for more efficient and safer gene transfection. The negatively charged ICG serves a dual purpose: neutralizing PEI's excessive positive charges to reduce cytotoxicity and, under near-infrared irradiation, inducing local heating that enhances cell membrane permeability, thus facilitating the uptake of PI/pDNA complexes to boost transfection efficiency. Using pDNA encoding vascular endothelial growth factor as a model, our system shows enhanced transfection efficiency in vitro for hard-to-transfect endothelial cells, leading to improved cell proliferation and migration. Furthermore, in vivo studies reveal the therapeutic potential of this system in accelerating the healing of infected wounds by promoting angiogenesis and reducing inflammation. This approach offers a straightforward and effective method for gene transfection, showing potentials for tissue engineering and cell-based therapies.
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Verde de Indocianina , Plásmidos , Polietileneimina , Transfección , Verde de Indocianina/química , Verde de Indocianina/farmacología , Polietileneimina/química , Humanos , Transfección/métodos , Animales , Plásmidos/genética , Plásmidos/metabolismo , Plásmidos/química , Ratones , ADN/química , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Células Endoteliales de la Vena Umbilical Humana , Proliferación Celular/efectos de los fármacosRESUMEN
BACKGROUND: The role of intraoperative near-infrared fluorescence angiography with indocyanine green in reducing anastomotic leakage (AL) has been demonstrated in colorectal surgery, however, its perfusion assessment mode, and efficacy in reducing anastomotic leakage after laparoscopic intersphincteric resection (LsISR) need to be further elucidated. AIM: Aim was to study near-infrared fluorescent angiography to help identify bowel ischemia to reduce AL after LsISR. MATERIAL AND METHODS: A retrospective case-matched study was conducted in one referral center. A total of 556 consecutive patients with ultra-low rectal cancer including 140 patients with fluorescence angiography of epiploic appendages (FAEA)were enrolled. Perfusion assessment by FAEA in the monochrome fluorescence mode. Patients were divided into two groups based on perfusion assessment by FAEA. The primary endpoint was the AL rate within 6 months, and the secondary endpoint was the structural sequelae of anastomotic leakage (SSAL). RESULTS: After matching, the study group (n = 109) and control group (n = 190) were well-balanced. The AL rate in the FAEA group was lower before (3.6% vs. 10.1%, P = 0.026) and after matching (3.7% vs. 10.5%, P = 0.036). Propensity scores matching analysis (OR 0.275, 95% CI 0.035-0.937, P 0.039), inverse probability of treatment weighting (OR 0.814, 95% CI 0.765-0.921, P 0.002), and regression analysis (OR 0.298, 95% CI 0.112-0.790, P = 0.015), showed that FAEA was an independent protector factor for AL. This technique can significantly shorten postoperative hospital stay [9 (6-13) vs. 10 (8-13), P = 0.024] and reduce the risk of SSAL (1.4% vs. 6.0%, P = 0.029). CONCLUSIONS: Perfusion assessment by FAEA can achieve better visualization in LsISR and reduce the incidence of AL, subsequently avoiding SSAL after LsISR.
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Fuga Anastomótica , Angiografía con Fluoresceína , Laparoscopía , Neoplasias del Recto , Humanos , Fuga Anastomótica/prevención & control , Fuga Anastomótica/etiología , Masculino , Femenino , Persona de Mediana Edad , Laparoscopía/métodos , Estudios Retrospectivos , Neoplasias del Recto/cirugía , Angiografía con Fluoresceína/métodos , Anciano , Verde de Indocianina , Estudios de Casos y Controles , Canal Anal/cirugía , Canal Anal/irrigación sanguínea , Anastomosis Quirúrgica/métodos , Anastomosis Quirúrgica/efectos adversosRESUMEN
BACKGROUND: Anastomotic leakage is a severe postoperative complication in colorectal surgery and compromised bowel perfusion is considered a major contributing factor. Conventional methods to assess bowel perfusion have a low predictive value for anastomotic leakage. We therefore aimed to evaluate the efficacy of real-time assessment with near-infrared (NIR) fluorescence imaging with indocyanine green (ICG) in the prevention of anastomotic leakage. METHODS: This multicentre, randomised, controlled, phase 3 trial was done in eight hospitals in the Netherlands. We included adults (aged >18 years) who were scheduled for laparoscopic or robotic colorectal surgery (with planned primary anastomosis) for benign and malignant diseases. Preoperatively, patients were randomly assigned (1:1) to fluorescence-guided bowel anastomosis (FGBA) or conventional bowel anastomosis (CBA) by variable block randomisation (block sizes 4, 6, and 8) and stratified by site. The operating surgeon and investigators analysing the data were not masked to group assignment. Patients were unmasked after the surgical procedure or after study end. In the FGBA group, surgeons marked anastomosis levels per conventional perfusion assessment and then administered 5 mg of ICG by 2 mL intravenous bolus. They assessed bowel perfusion using NIR fluorescence imaging and adjusted (or kept) transection lines accordingly. Only conventional methods for bowel perfusion assessment were used in the CBA group. The primary outcome was the difference in the rate of clinically relevant anastomotic leakage (ie, requiring active therapeutic intervention but manageable without reoperation [grade B] or requiring reoperation [grade C], per the International Study Group of Rectal Cancer) between the FGBA group and the CBA group within 90 days post-surgery. The primary outcome and safety were assessed in the intention-to-treat population. This study was registered with ToetsingOnline.nl (NL7502) and ClinicalTrials.gov (NCT04712032) and is complete. FINDINGS: Between July 2, 2020, and Feb 21, 2023, 982 patients were enrolled, of whom 490 were assigned to FGBA and 492 were assigned to CBA. After excluding 51 patients, the intention-to-treat population comprised 931 (463 assigned FGBA and 468 assigned CBA). Patients had a median age of 68·0 years (IQR 59·0-75·0) and 485 (52%) were male and 446 (48%) were female. Ethnicity data were not available. The overall 90-day rate of clinically relevant anastomotic leakage was not significantly different between the FGBA group (32 [7%] of 463 patients) and the CBA group (42 [9%] of 468 patients; relative risk 0·77 [95% CI 0·50-1·20]; p=0·24). No adverse events related to ICG use were observed. 313 serious adverse events in 229 (25%) patients were at 90-day follow-up (159 serious adverse events in 113 [24%] patients in the FGBA group and 154 serious adverse events in 116 [25%] patients in the CBA group). 18 (2%) people died by 90 days (ten in the FGBA group and eight in the CBA group). INTERPRETATION: ICG NIR fluorescence imaging did not reduce 90-day anastomotic leakage rates in this trial across all types of colorectal surgeries. Further research should be done in subgroups, such as rectosigmoid resections, for which evidence suggests ICG NIR might be beneficial. FUNDING: Olympus Medical, Diagnostic Green, and Intuitive Foundation.
Asunto(s)
Anastomosis Quirúrgica , Fuga Anastomótica , Verde de Indocianina , Humanos , Verde de Indocianina/administración & dosificación , Fuga Anastomótica/prevención & control , Fuga Anastomótica/etiología , Femenino , Masculino , Persona de Mediana Edad , Anciano , Anastomosis Quirúrgica/efectos adversos , Anastomosis Quirúrgica/métodos , Colorantes/administración & dosificación , Imagen Óptica/métodos , Laparoscopía/métodos , Laparoscopía/efectos adversos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Procedimientos Quirúrgicos Robotizados/métodos , Imagen de Perfusión/métodos , Cirugía Colorrectal/efectos adversos , Cirugía Colorrectal/métodos , Países Bajos/epidemiologíaRESUMEN
Although targeted therapy has revolutionized oncotherapy, engineering a versatile oncotherapy nanoplatform integrating both diagnostics and therapeutics has always been an intractable challenge to overcome the limitations of monotherapy. Herein, a theranostics platform based on DI/MP-MB has successfully realized the fluorescence detection of disease marker miR-21 and the gene/photothermal/chemo triple synergetic cancer therapy, which can trace the tumor through photothermal and fluorescence dual-mode imaging and overcome the limitations of monotherapy to improve the treatment efficiency of tumors. DI/MP-MB was prepared by magnetic mesoporous silicon nanoparticles (M-MSNs) loaded with doxorubicin (Dox) and new indocyanine green (IR820), and subsequently coating polydopamine as a "gatekeeper", followed by the surface adsorbed with molecular beacons capable of targeting miR-21 for responsive imaging. Under the action of enhanced permeability retention and external magnetic field, DI/MP-MB were targeted and selectively accumulated in the tumor. MiR-21 MB hybridized with miR-21 to form a double strand, which led to the desorption of miR-21 MB from the polydopamine surface and the fluorescence recovery to realize gene silencing and fluorescence imaging for tracking the treatment process. Meanwhile, with the response to the near-infrared irradiation and the tumor's microacid environment, the outer layer polydopamine will decompose, releasing Dox and IR820 to realize chemotherapy and photothermal therapy. Finally, the ability of DI/MP-MB to efficiently suppress tumor growth was comprehensively assessed and validated both in vitro and in vivo. Noteworthily, the excellent anticancer efficiency by the synergistic effect of gene/photothermal/chemo triple therapy of DI/MP-MB makes it an ideal nanoplatform for tumor therapy and imaging.
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Doxorrubicina , Indoles , MicroARNs , Imagen Multimodal , Polímeros , Silicio , Nanomedicina Teranóstica , Indoles/química , Polímeros/química , Silicio/química , Humanos , Animales , Doxorrubicina/química , Doxorrubicina/farmacología , Ratones , Porosidad , Verde de Indocianina/química , Ratones Desnudos , Ratones Endogámicos BALB C , Nanopartículas/química , Línea Celular Tumoral , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Imagen Óptica , Propiedades de SuperficieRESUMEN
BACKGROUND: The extent of perfusion of a deep inferior epigastric artery perforator (DIEP) flap is a primary concern for surgeons. This study aimed to determine whether the flap area or volume can be estimated using perforator and flap characteristics. METHODS: Intraoperative flap perfusion was assessed using indocyanine green angiography in patients who underwent DIEP flap breast reconstruction between November 2018 and February 2023. The area perfused by a single dominant perforator was delineated on the surface of the flap and measured using the ImageJ software. Multiple linear regression analysis was conducted to estimate the 'perfusion ratio,' defined as the perfused area divided by the total flap area. Potential predictor variables included flap size (cm2), flap thickness (mm), perforator diameter (mm), perforator rows (medial/lateral), vertical location of perforator (at or above/below the umbilicus), and perforator eccentricity (vertical distance from upper flap margin to perforator, cm). RESULTS: In total, 101 patients were included in this analysis. The mean 'perfusion ratio' was 67.8% ± 11.5%, predicted by perforator diameter (p = 0.022) and vertical location below umbilicus (p < 0.001) with positive correlations and negatively correlated with flap thickness (p = 0.003) in the multivariable analysis. Both perfusion area and weight were predicted by perforator diameter, vertical location of perforator, flap size, and flap thickness (p < 0.001). The coefficient of determination (adjusted R2) for prediction of perfusion weight was higher than that for the perfusion area (75.5% vs. 69.4%). CONCLUSIONS: Flap volume, rather than area, is determined by a perforator of a given diameter and location.
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Arterias Epigástricas , Mamoplastia , Colgajo Perforante , Humanos , Colgajo Perforante/irrigación sanguínea , Femenino , Arterias Epigástricas/trasplante , Mamoplastia/métodos , Persona de Mediana Edad , Adulto , Verde de Indocianina , Angiografía/métodos , Estudios RetrospectivosRESUMEN
Antibody therapy of anti-HER2 monoclonal antibody (mAb) has been an important strategy in treating HER2-positive cancers. However, the efficacy is restricted by many factors, including the level of HER2 expressed by tumor cells and antibody resistance. To overcome these and boost the efficacy, a novel nanoparticle (NP) was constructed in this study for combined antibody therapy of antibody and photothermal therapy (PTT). This novel NP was assembled from 1-pyrenecarboxylic acid (PCA) functionalized anti-HER2 mAb and indocyanine green (ICG), a photothermal transduction agents (PTA), by non-covalent interactions, which was named as Anti-HER2 mAb-pyrene-indocyanine green (H-P-I). Notably, the constructed H-P-I NP not only maintained the affinity and cytotoxicity of anti-HER2 mAb, but also exhibited high photothermal conversion efficiency mediated by ICG. Both in vitro and in vivo assessments confirmed that compared with monotherapy of antibody or ICG, H-P-I demonstrated preferable efficacy in treating HER2-positive cancers. Further biochemistry analysis and pathological analysis ensured the biosafety of H-P-I administration. Taked together, this study proposes a feasible method for constructing tumor-targeted nano PTA based on anti-HER2 mAb through supramolecular self-assembly strategy, achieving synergistic antibody photothermal anticancer treatment, which has the potential to be a promising candidate for combination therapy of HER2-positive cancers.
Asunto(s)
Inmunoconjugados , Terapia Fototérmica , Receptor ErbB-2 , Receptor ErbB-2/metabolismo , Receptor ErbB-2/inmunología , Receptor ErbB-2/antagonistas & inhibidores , Humanos , Terapia Fototérmica/métodos , Animales , Inmunoconjugados/farmacología , Inmunoconjugados/química , Inmunoconjugados/uso terapéutico , Ratones , Línea Celular Tumoral , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/química , Nanopartículas/química , Verde de Indocianina/química , Verde de Indocianina/farmacología , Verde de Indocianina/uso terapéutico , Femenino , Neoplasias/terapia , Neoplasias/inmunologíaRESUMEN
Subcutaneous (SC) administration of chemotherapeutics combined with near-infrared (NIR) light activation can effectively target skin tumors by triggering localized drug release and enhancing cytotoxic effects. In this study, we developed NIR-responsive indocyanine green (ICG) and the chemotherapeutic agent doxorubicin (Dox) loaded into gelatin nanoparticles (NPs) for SC delivery in a skin tumor-bearing mouse model. Histological examination (hematoxylin and eosin staining) confirmed the successful delivery and swelling behavior of the Dox/ICG-loaded gelatin NPs at the SC site. In vitro and in vivo experiments demonstrated that NIR activation of the Dox/ICG-loaded gelatin NPs generated significant photothermal heat (48 and 46 °C), leading to targeted drug release and a substantial reduction in skin tumor size (from 15 to 3 mm3). Our findings suggest that this dual-modality approach of SC chemotherapeutic administration and NIR-triggered photothermal therapy can concentrate cytotoxic drugs at the tumor site, offering a promising strategy for improving skin cancer treatment.