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BACKGROUND:Photothermal therapy is a novel tumor treatment strategy that uses photothermal agents to transform light energy into heat energy to accomplish non-invasive tumor ablation.The rise of photothermal therapy and nanotechnology has provided a new perspective on breast cancer treatment.OBJECTIVE:To prepare a new type of near-infrared biomimetic nanoprobe that has been modified by breast cancer cell membrane,to investigate the effect of near-infrared fluorescence/ultrasound imaging in vitro,and to observe its targeting ability and photothermal therapy effect on homologous tumor cells in vitro.METHODS:Organic small molecule ITIC-4CI with A-D-A structure was used as photothermal agents;polylactic acid/glycolic acid copolymer as nanocarrier;4T1 cell membrane of mouse breast cancer cells as a surface modifier of nanoparticles;perfluorohexane(PFH)was loaded.A novel near-infrared biomimetic nanoprobe(4T1m/ITIC-4CI/PFH)was prepared by the double emulsion evaporation method and sonication method.The basic characterization of the nanoprobe and the homologous targeting ability were detected.The photothermal properties and photothermal stability of the probe were investigated,and the near-infrared fluorescence/ultrasound imaging effect of the probe under laser irradiation was observed.The CCK-8 assay and calcein/propidium iodide staining were used to assess the efficacy of photothermal therapy.RESULTS AND CONCLUSION:(1)The prepared 4T1m/ITIC-4CI/PFH nanoprobes had uniform size,high stability,and an average particle size of(92.7±2.3)nm.The probe's protein composition was identical to that of the 4T1 cell membrane.The nanoprobe's ability to target homologous 4T1 cells was validated by an in vitro cell uptake assay.(2)The nanoprobe had a red-shift absorption spectrum and tail emission extending to the near-infrared-Ⅱ,which emitted a bright near-infrared-Ⅱ fluorescence signal under laser irradiation.(3)After laser irradiation,the nanoprobe 4T1m/ITIC-4CI/PFH could be turned into microbubbles and enhanced ultrasound imaging.The results of CCK-8 assay and calcein/propidium iodide staining showed that the nanoprobe 4T1m/ITIC-4CI/PFH had an obvious photothermal killing effect on 4T1 cells.(4)The results show that the nanoprobe 4T1m/ITIC-4CI/PFH has the ability to target homologous tumors and enhance near-infrared-Ⅱ fluorescence imaging/ultrasound imaging and photothermal therapy effects.
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BACKGROUND:Existing neuroimaging techniques,including magnetic resonance imaging,computed tomography,and high-resolution ultrasound,lack the capability to provide real-time intraoperative positioning images to surgeons.However,the clinical implementation of near-infrared fluorescence imaging technology has made it possible to directly visualize surgical target areas,offering a novel solution for real-time nerve identification during surgery. OBJECTIVE:To provide a summary and overview of the research progress in near-infrared fluorescence imaging technology for intraoperative neuroimaging. METHODS:The first author used the computer to search for the documents published from January 2010 to July 2023 in WanFang,CNKI,and PubMed with the key words of"near-infrared fluorescence imaging,optical imaging,nerve imaging"in Chinese and English.A few classic old documents were also included.Initial screening was performed by reading the titles and abstracts;duplicate,low-quality,and irrelevant content documents were excluded.A total of 69 articles were finally included for review. RESULTS AND CONCLUSION:Near-infrared fluorescence imaging guided by indocyanine green has been clinically used to identify and locate tubular organs such as blood vessels,ureters,and bile ducts,as well as various tumors during surgery.This technique is currently considered a well-established imaging method in precision surgery.In the field of intraoperative neurofluorescence imaging,indocyanine green is currently the only near-infrared fluorescent dye used in clinical research.The ideal neuroimaging agent should possess certain characteristics,including easy administration in the perioperative period,logD between 0.5 and 3 at pH=7.4,molecular mass below 500 Da,excitation and emission wavelengths within the near-infrared window,long-term retention in nerve tissue,high signal-to-background ratio,and high safety.In the future,the development of near-infrared neurofluorescence imaging agents should focus on synthesizing complexes of indocyanine green and neural-specific targets.This technology not only enables intraoperative neurofluorescence imaging,but also holds promising prospects for in-situ monitoring of nerve regeneration and diagnosis of neurological diseases.
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Objective A novel compound based on near-infrared fluorescence (NIRF) probe was prepared to achieve dynamic monitoring of an inflammatory brain edema model in mice and real-time evaluation of therapeutic effects throughin vivo imaging.Methods The NIRF probe IR-783 was chemically linked with clinical brain edema therapeutic drug furosemide (FSM) to obtain the new compound, IR-783-FSM. The ultraviolet fluorescence properties of the compound were evaluated using an ultraviolet spectrophotometer. The uptake of the compound by mouse macrophage cells RAW 264.7 was detected with in vitro cellular experiments. Its cytotoxicity was evaluated through CCK8 assays. A brain edema model was established in BALB/c mice via intraperitoneal injection of lipopolysaccharide (LPS), confirmed by HE staining and dry-wet weight methods for brain tissues. The mice in the brain edema model were divided into control group, IR-783, and IR-783-FSM treatment groups, receiving intraperitoneal injections of PBS, IR-783, and IR-783-FSM, respectively. Real-time in vivo fluorescence imaging was then performed. The mice in each group were euthanized after 10 hours. Ex vivo brain imaging and dry-wet weight measurements were performed to observe the NIRF imaging characteristics and therapeutic effects of IR-783-FSM on brain edema model.Results The newly synthesized compound, IR-783-FSM, retained the excellent near-infrared fluorescence characteristics of IR-783. It could target mouse macrophages with an IC50 of 48.82 µmol/L. A brain edema model could be successfully constructed with intraperitoneal injection of LPS, with significantly higher brain tissue water content compared to the control group (P<0.01). In vivo imaging showed that IR-783-FSM had a significantly stronger fluorescence signal in the brain edema model than IR-783. Compared to the control group, the brain water content was significantly reduced in the 2, 5, and 8 mmol/L IR-783-FSM treatment groups (P<0.01).Conclusion The newly synthesized NIRF probe IR-783-FSM facilitates dynamic monitoring of brain edema and real-time evaluation of therapeutic effects.
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Near-infrared fluorescence imaging (NIRFI) is a new noninvasive detection and diagnosis technology, with the continuous development of NIRFI technology, now widely used in the clinic, characterized by high sensitivity, high penetration, no harmful radiation and simple equipment operation. This article describes the recent applications of NIRFI in the diagnosis and treatment of breast cancer and looks at future developments and perspectives in this field.
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Objective @# To investigate the application of indocyanine green in near-infrared fluorescence imaging to determine the scope of necrotic bone resection in osteoradionecrosis of the jaw and to provide a reference for clinicians@*Methods @#Eight patients with osteoradionecrosis of the jaws were enrolled. Indocyanine green was intravenously injected through the elbow vein 10 minutes before osteotomy. After conservative resection of necrotic bone lesions based on imaging results, the scope of potential dead bone resection in the area of low fluorescence intensity was gradually expanded at an initial distance of 0.3 cm. Near-infrared fluorescence imaging and fluorescence intensity determination of bone cross-section were performed before and after extended resection. Statistical differences were analyzed. All patients with osteonecrosis underwent regular follow-up to evaluate the postoperative efficacy@*Results@#Indocyanine green was injected into all 8 patients with osteoradionecrosis for near-infrared fluorescence imaging and the scans were clear; the fluorescence intensity of fresh bone wounds with an expanded mandibular resection range of (0.95 ± 0.14) cm was (226.2 ± 15.8) au, which was higher than that based on intraoperative macroscopic observation and radiological results (108.8 ± 3.4) au, (t = 20.718, P<0.001). The postoperative follow-up improvement rate of 8 patients was 87.5%.@* Conclusion @#Near-infrared fluorescence imaging with indocyanine green can assist in the successful removal of necrotic bone until fresh bleeding of the jaw wound occurs, which has important clinical value in defining the resection range of osteoradionecrosis of the jaw.
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Indocyanine green (ICG) is the most commonly used near-infrared fluorescent (NIRF) dye in clinical practice, and its mediated near-infrared fluorescence imaging technology is gradually applied in clinical practice. It has shown great potential in invasive surgery (MIS) and is expected to become the standard technology for surgical diagnosis and treatment of diseases. The clinical application of ICG fluorescence laparoscopy is reviewed here.
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Indocyanine Green , Fluorescence , Laparoscopy , Coloring AgentsABSTRACT
Objective:To investigate the feasibility and clinical significance of near-infrared fluorescence positive imaging combined with intraoperative rapid parathyroid hormone (PTH) determination in identification and function protection of the parathyroid gland during thyroidectomy.Methods:According to the inclusion and exclusion criteria, patients in the Affiliated Lihuili Hospital of Ningbo University, who needed bilateral thyroidecto-my and central lymph node dissection due to suspected bilateral thyroid cancer from Mar. 2020 to Oct. 2020 were selected for a prospective clinical study. They were randomly divided into the study group (near-infrared fluorescence positive imaging combined with intraoperative rapid PTH determination) and the control group (intraoperative experience identification) . The number of parathyroid glands found during operation, PTH before and after the operation, blood calcium, blood phosphorus, the presence of parathyroid tissues in routine pathological section examinations, and postoperative symptoms were collected. SPSS 25.0 statistical software was used for analysis, the measurement data were expressed by mean±standard deviation ( ± s) , t test was used for comparison between groups, and χ2 test was used for counting date. Results:In the study group of 33 cases, 135 suspicious parathyroid glands were exhibited during operation, with an average of (4.09±0.52) ; Hand and foot numbness occurred in 1 case (3.03%) ; On the 1st after the operation, PTH was (23.68±9.48) ng/L. In the control group of 31 cases, 109 parathyroid glands were identified by naked eyes, with an average of (3.52±0.63) ; Hand and foot numbness occurred in 6 cases (19.35%) ; On the 1st after the operation, PTH was (17.93±11.58) ng/L. The differences were statistically significant ( P<0.05) . But no statistical significance was found in operation duration (79.45±30.18) min, postoperative hospitalization days (5.85±2.27) days, PTH (27.10±9.80, 33.08±10.21) ng/L, blood calcium (2.11±0.10,2.25±0.09) mmol/L, and blood phosphorus (1.20±0.20,1.15±0.12) mmol/L on the 3rd day and the 6th month after the operation. Conclusion:Near-infrared fluorescence positive imaging combined with intraoperative rapid PTH determination can improve the recognition rate of the parathyroid gland and reduce postoperative complications, which is a safe, effective and rapid method for intraoperative parathyroid gland recognition.
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Objective: Local recurrence is the main cause of treatment failure in patients with oral squamous cell carcinoma (OSCC). This study was proposed to investigate the feasibility of near infrared fluorescence (NIF) via indocyanine green (ICG) for monitoring surgical marginal in operation for OSCC patients. Methods: In 35 patients with OSCC treated surgically in the Department of Oral and Maxillofacial Surgery, Nanjing University School of Medicine, from January 2019 to June 2020, ICG (0.75 mg/kg) was administered intravenously via elbow vein at (12±1) hours before surgery, and NIF was performed intraoperatively on the surgical field and the cut edge of the surgically excised specimen, and fluorescence intensity was measured for OSCC tissue and normal oral mucosa, abnormal fluorescence signals were taken and subjected to rapid cryopathological examination. Correlation between NIF tumor boundary grading and pathological tumor boundary grading was analyzed by Spearman correlation analysis. Results: Clear ICG NIF was obtained for tumor lesions in all 35 patients, with a positive rate of 100%. The fluorescence intensity of OSCC tissue was (412.73±146.56) au, which was higher than that of normal oral mucosa tissue [(279.38±82.56) au, P<0.01]. Abnormal fluorescence signals were detected at the tumor bed and the cut edge of the surgical resection specimen in 4 patients, of which 2 cases were pathologically confirmed as cancer cell residue and 2 cases as inflammatory cell infiltration. The rate of positive detection of cut margins using ICG NIF technique in OSCC was 5.7% (2/35). Twenty of the 35 OSCC patients had grade 1, 11 of grade 2, and 4 of grade 3 tumor borders revealed by NIF of surgical resection specimens, which was positively correlated with pathological tumor border (r=0.809, P<0.001). Conclusions: ICG NIF technique can effectively detect the residual cancer cells at the incision margin, which is of great clinical value in reducing local recurrence of OSCC after surgery due to intraoperative cancer residue.
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Humans , Carcinoma, Squamous Cell/surgery , Head and Neck Neoplasms , Indocyanine Green , Margins of Excision , Mouth Neoplasms/surgery , Neoplasm, Residual , Optical Imaging/methods , Squamous Cell Carcinoma of Head and Neck/surgeryABSTRACT
The glymphatic system is a fluid dynamics network that is important for maintaining homeostasis of the brain, and it is also a new target for the treatment of various central nervous system diseases. The crucial point regarding research into the glymphatic system is the microhydrodynamics of the cerebrospinal fluid tracer. This review summarizes the emerging technologies, such as magnetic resonance technology, two photon microscopic imaging technology, near infrared fluorescence imaging technology, and transcranial macroscopic imaging, and summarizes its research applications and technical advantages to provide methodological strategies for basic and clinical research on glymphatic system function.
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The preliminary screening of oral cancer mostly depends on the experience of clinicians, The surgical margin of tumor is mostly based on physical examination and preoperative imaging examination. It lacks real-time and objective intraoperative evaluation methods. Indocyanine green (ICG), as a safe and pollution-free organic fluorescent pigments, combined with near-infrared fluorescence imaging can be applied in the screening of early oral cancer, the determination of tumor resection margins, sentinel lymph node biopsy, cervical lymph node dissection, targeted chemotherapy, and other aspects. Near-infrared fluorescence imaging may become a key link in the early diagnosis and accurate treatment for oral cancer in the future.
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Humans , Indocyanine Green , Lymph Nodes , Mouth Neoplasms/therapy , Optical Imaging , Sentinel Lymph Node BiopsyABSTRACT
Fluorescence imaging has been widely used in the fields of biomedicine and clinical diagnosis. Compared with traditional fluorescence imaging in the visible spectral region (400-760 nm), near-infrared (NIR, 700-1 700 nm) fluorescence imaging is more helpful to improve the signal-to-noise ratio and the sensitivity of imaging. Highly-sensitive fluorescent probes are required for high-quality fluorescence imaging, and the rapid development of nanotechnology has led to the emergence of organic dyes with excellent fluorescent properties. Among them, organic fluorescent probes with the advantages of high safety, good biocompatibility, and high optical stability, are more favorable than inorganic fluorescent probes. Therefore, NIR fluorescence imaging assisted with organic fluorescent probes can provide more structural and dynamic information of biological samples to the researchers, which becomes a hot spot in the interdisciplinary research field of optics, chemistry and biomedicine. This review summarizes the application of NIR organic fluorescent probes in cervical cancer imaging. Several typical organic fluorescent probes (such as indocyanine green, heptamethine cyanine dye, rhodamine and polymer fluorescent nanoparticles) assisted NIR fluorescence imaging and their applications in cervical cancer diagnosis were introduced, and the future development and application of these techniques were discussed.
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Female , Humans , Fluorescent Dyes , Nanoparticles , Optical Imaging , Polymers , Uterine Cervical Neoplasms/diagnostic imagingABSTRACT
OBJECTIVE@#To evaluate the clinical application of indocyanine green (ICG) visualization by near infrared fluorescence laparoscopy (NIFL) in complex upper urinary tract reconstructions surgery.@*METHODS@#This was a retrospective study of 7 patients who underwent complex surgeries of ureteral reconstruction between May 2019 and October 2019. There were 6 males and 1 female with the age ranging from 24 to 57 years (median age was 47 years). There were 5 cases of right ureteral strictures, of which 3 were proximal ureteral strictures and 2 were multiple and long ureteral strictures caused by radiotherapy. There were 2 cases of left ureteral strictures, of which 1 was ureteropelvic junction stricture and 1 was proximal ureteral stricture. There were 4 cases of secondary repair operations and 3 cases of primary operations. All the patients underwent laparoscopic surgery via the abdominal approach. ICG was injected into the ureter via nephrostomy tube during the operations, and the diseased ureter was identified by NIFL. Among the patients, 2 cases underwent IUPU (Institute of Urology, Peking University) modified ileal ureter replacement, 2 cases underwent ureteroureterostomy, 2 cases underwent appendiceal onlay flap ureteroplasty, and 1 case underwent lingual mucosa onlay flap ureteroplasty.@*RESULTS@#All the operations were successfully completed without open conversion. The localization and separation of ureteral lesions were completed under NIFL. The mean operative time was 187 (135-300) min. The duration of ureteral separation was 15-27 min, and the mean time was 18 min. The estimated blood loss was 15-200 mL, the mean estimated blood loss was 50 mL. There was one patient with ileal ureter replacement who had fever after surgery and responded well to antibiotics. The mean (range) length of postoperative hospital stay was 7 (6-10) days and no postoperative complications of a high grade (Clavien-Dindo Ⅲ and Ⅳ) occurred. Up to now, the mean follow-up duration was 9 (6-11) months, and no indocyanine green toxicity occurred. All D-J stents and nephrostomy were removed successfully 2 months after the operation. Ultrasound showed no obvious hydronephrosis, and CTU (computed tomography urography) showed that the urinary tract was unobstructed and the kidney function was normal.@*CONCLUSION@#The application of ICG in the complex upper urinary tract reconstructive surgery is a safe and easy method to help surgeon to identify the ureter which may reduce the risk of iatrogenic damage and protect the ureteral blood supply.
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Adult , Female , Humans , Male , Middle Aged , Young Adult , Indocyanine Green , Laparoscopy , Retrospective Studies , Ureter/surgery , Ureteral Obstruction , Urologic Surgical ProceduresABSTRACT
Near-infrared fluorescence (NIRF) imaging is an emerging technology that aids in real-time intraoperative navigation. NIRF uses fluorescent dyes and probes to obtain real-time anatomical and functional information of blood and lymphatic vasculature and specific tissues during surgery. It can identify small cancerous growths and tumor margins that cannot be normally detected by traditional methods, thus providing the surgeons with a perioperative, anatomical guidance and identification modality to make correct intraoperative decisions. NIRF is promising owing to the following aspects: real-time, sensitive, safe, non-invasive, relatively cheap, and non-ionizing; it has the potential to bring a revolution in the existing surgical techniques. This article comprehensively reviews the basic principles of NIRF imaging technology, the clinical progress in real-time guided tumor resection, sentinel lymph node mapping for cancer staging, and protection of critical anatomical structures during surgery. Furthermore, this review discusses the advantages and limitations of NIRF technology and potential future prospects for its application.
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@#Alzheimer′s disease(AD)is a chronic neurodegenerative diseasecommonly seen in the elderlys. Several therapeutic drugs have failed in phase III clinical trials in recent years and there have been no efficient treatment for AD currently. Thus, there has been an urgent need for the effective methods of AD diagnosis at early stage. Developingnear-infrared fluorescentprobes for AD hallmarks detection has been a promising research field. In this review, we summarized a variety of near-infrared fluorescence(NIRF)probes reported in the past decade, which capable of detecting β-amyloid, Tau protein and reactive oxygen species, including their chemical strucutres、optical properties, in vitro and in vivo studies. Furthermore, we alsoraised some new directions for AD diagnosing. We believe that these new directions raised herein will benefit the future development of NIRF probes in the field of AD research.
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BACKGROUND: For the bone-specific imaging, a structure-inherent targeting of bone tissue recently has been reported a new strategy based on incorporation of targeting moieties into the chemical structure of near-infrared (NIR) contrast agents, while conventional methods require covalent conjugation of bone-targeting ligands to NIR contrast agents. This will be a new approach for bone-targeted imaging by using the bifunctional NIR contrast agents. METHODS: The goal of this review is to provide an overview of the recent advances in optical imaging of bone tissue, highlighting the structure-inherent targeting by developing NIR contrast agents without the need for a bone-targeting ligand such as bisphosphonates. RESULTS: A series of iminodiacetated and phosphonated NIR contrast agents for the structure-inherent targeting of bone tissue showed excellent bone-targeting ability in vivo without non-specific binding. Additionally, the phosphonated NIR contrast agents could be useful in the diagnosis of bone metastasis. CONCLUSION: By developing bone-targeted NIR contrast agents, optical imaging of bone tissue makes it very attractive for preclinical studies of bone growth or real-time fluorescence guided surgery resulting in high potential to shift the clinical paradigms.
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Bone and Bones , Bone Development , Contrast Media , Diagnosis , Diphosphonates , Fluorescence , Ligands , Neoplasm Metastasis , Optical Imaging , Surgery, Computer-AssistedABSTRACT
Multi-modal fusion molecular imaging technology integrates the advantages of a variety of molecular imaging techniques,and has become a hotspot and trend in the field of molecular imaging. Heptamethine cyanine dye is a class of novel near-infrared fluorescence(NIRF)dye with tumor targeting properties. With its unique optical properties, the dye has broad application prospects in tumor molecular imaging, targeted therapy and drug delivery system. Nano-materials containing heptamethine cyanine dye can be used for NIRF/MRI dual-modal imaging. NIRF/PET dual-modal imaging can be achieved after labeling with nuclides. Conjugated with chemotherapy drugs,targeted delivery of anti-tumor drugs can also be achieved. Complexes of multiple heptamethine cyanine dyes have been used for multi-modal imaging as a new strategy for photothermal therapy,photodynamic therapy and combined treatment of tumors.
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Objective To establish and evaluate a patient-derived orthotopic xenograft ( PDOX ) model of pancreatic cancer. Methods Tissues of patient-derived pancreatic tumor were transplanted into nude mouse pancreas by surgery. The PDOX models were evaluated by the small animal near infrared fluorescence ( NIRF) optical imaging and PET/CT. The traceability of PDOX models was detected by STR technology, and the pathological changes were observed by H&E staining, immunohistochemistry, and serum level of CA19-9 was detected by ELISA. Results Apparent NIRF were observed to be accumulated in pancreatic site by optical imaging system. The location and size of the xenografts tumor were revealed by fluorescence intensity. The PET/CT images with 18F-FDG molecular probe confirmed the tumor's location and size. Ex vivo NIRF imaging of isolated organ further showed the tumor formation. The traceability of PDOX models was 99. 99% with human origin. H&E staining pathology and immunohistochemistry indicated the pancreatic cancer characteristics. The high serum level of ca19-9 confirmed the mice bearing tumor. Conclusions Pancreatic PDOX models are successfully established in this study, and it can be evaluated comprehensively by NIRF optical imaging and PET/CT, providing an appropriate platform for further research of pancreatic cancer.
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Multimodality optical imaging probes have emerged as powerful tools that improve detection sensitivity and accuracy, important in disease diagnosis and treatment. In this review, we focus on recent developments of optical fluorescence imaging (OFI) probe integration with other imaging modalities such as X-ray computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), single-photon emission computed tomography (SPECT), and photoacoustic imaging (PAI). The imaging technologies are briefly described in order to introduce the strengths and limitations of each techniques and the need for further multimodality optical imaging probe development. The emphasis of this account is placed on how design strategies are currently implemented to afford physicochemically and biologically compatible multimodality optical fluorescence imaging probes. We also present studies that overcame intrinsic disadvantages of each imaging technique by multimodality approach with improved detection sensitivity and accuracy.
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This study investigated the anti-cancer potential of a near-infrared fluorescence (NIRF) molecule conjugated with Cetuximab (Cetuximab-NIRF) in six-week-old female BALB/c athymic (nu+/nu+) nude mice. A431 cells were cultured and injected into the animals to induce solid tumors. Paclitaxel (30 mg/kg body weight (BW)), Cetuximab (1 mg/kg BW), and Cetuximab-NIRF (0.25, 0.5 and 1.0 mg/kg BW) were intraperitoneally injected twice a week into the A431 cell xenografts of the nude mice. Changes in BW, tumor volume and weight, fat and lean mass, and diameter of the peri-tumoral blood vessel were determined after two weeks. Tumor volumes and weights were significantly decreased in the Cetuximab-NIRF (1 mg/kg BW) group compared with the control group (P < 0.001). Lean mass and total body water content were also conspicuously reduced in the Cetuximab-NIRF (1 mg/kg BW) group compared with the vehicle control group. Peri-tumoral blood vessel diameters were very thin in the Cetuximab-NIRF groups compared with those of the paclitaxel group. These results indicate that the conjugation of Cetuximab with NIRF does not affect the anti-cancer potential of Cetuximab and NIRF can be used for molecular imaging in cancer treatments.
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Animals , Female , Humans , Mice , Blood Vessels , Body Water , Body Weight , Cetuximab , Fluorescence , Heterografts , Mice, Nude , Molecular Imaging , Paclitaxel , Tumor Burden , Weights and MeasuresABSTRACT
Objective To study the application of hepatamethine cyanine near-infrared fluorescence (NIRF) dye IR-783 in the mouse models of human liver cancer exenografts, and to analyze the molecular mechanisms of the NIRF dye targeting tumor cells.Methods Luciferase-tagged HepG2 cells were inoculated subcutaneously into the nude mice.We detected the correlation of NIRF intensity and bioluminescence intensity (BIL) in the tumor region.Patient-derived xenograft (PDX) model was established in mouse by subrenal capsular implantation of clinic liver cancer specimen.After injecting the IR-783 dye, the interface between mouse kidney and the xenograft tumors was confirmed by NIRF analysis, and the tumor tissue in kidney was observed by pathology using H&E staining.The expression of CEA, AFP, HIF1α and OATP3A1 in the liver cancer tissue was detected by immunohistochemical staining.The intracellular retention of NIRF dyes was observed under fluorescence microscope after adding Mito Tracker or Lyso Tracker into cultured HepG2 cells.We added IR-783 in a co-culture system of HCCs and normal liver cells to test the specifical identification ability of IR-783 of the liver cancer cells.Results There was a good correlation between NIRF intensity and BIL intensity of the subcutaneous liver cancer xenograft region in nude mice.The margin between the mouse kidney tissue and xenograft tumors was clearly identified by IR-783.Compared with normal kidney tissue, CEA, HIF1α, OATP3A1 and AFP were highly expressed in the tumor region detected by IHC staining.The NIRF dye IR-783 was mainly accumulated in the mitochondria and lysosomes of cancer cells.GFP-tagged HepG2 cells could be recognized directly, whereas red fluorescence was not detected in normal liver cells.Conclusions IR-783 is a novel near-infrared fluorescent dye with tumor targeting and imaging properties.Its targeting ability may be related to the high expression of HIF1α and OATP3A1 in the liver cancer tissue.