Targeted imaging of αvβ3 expressing sarcoma tumor cells in vivo in pre-operative setting using near infrared: A potential tool to reduce incomplete surgical resection

Bone ◽  
2014 ◽  
Vol 62 ◽  
pp. 71-78 ◽  
Author(s):  
Aurelie Dutour ◽  
Veronique Josserand ◽  
Delphine Jury ◽  
Stephanie Guillermet ◽  
Anne Valerie Decouvelaere ◽  
...  
2011 ◽  
Vol 115 (6) ◽  
pp. 1131-1138 ◽  
Author(s):  
Nikolay L. Martirosyan ◽  
Daniel D. Cavalcanti ◽  
Jennifer M. Eschbacher ◽  
Peter M. Delaney ◽  
Adrienne C. Scheck ◽  
...  

Object Infiltrative tumor resection is based on regional (macroscopic) imaging identification of tumorous tissue and the attempt to delineate invasive tumor margins in macroscopically normal-appearing tissue, while preserving normal brain tissue. The authors tested miniaturized confocal fiberoptic endomicroscopy by using a near-infrared (NIR) imaging system with indocyanine green (ICG) as an in vivo tool to identify infiltrating glioblastoma cells and tumor margins. Methods Thirty mice underwent craniectomy and imaging in vivo 14 days after implantation with GL261-luc cells. A 0.4 mg/kg injection of ICG was administered intravenously. The NIR images of normal brain, obvious tumor, and peritumoral zones were collected using the handheld confocal endomicroscope probe. Histological samples were acquired from matching imaged areas for correlation of tissue images. Results In vivo NIR wavelength confocal endomicroscopy with ICG detects fluorescence of tumor cells. The NIR and ICG macroscopic imaging performed using a surgical microscope correlated generally to tumor and peritumor regions, but NIR confocal endomicroscopy performed using ICG revealed individual tumor cells and satellites within peritumoral tissue; a definitive tumor border; and striking fluorescent microvascular, cellular, and subcellular structures (for example, mitoses, nuclei) in various tumor regions correlating with standard clinical histological features and known tissue architecture. Conclusions Macroscopic fluorescence was effective for gross tumor detection, but NIR confocal endomicroscopy performed using ICG enhanced sensitivity of tumor detection, providing real-time true microscopic histological information precisely related to the site of imaging. This first-time use of such NIR technology to detect cancer suggests that combined macroscopic and microscopic in vivo ICG imaging could allow interactive identification of microscopic tumor cell infiltration into the brain, substantially improving intraoperative decisions.


2013 ◽  
Vol 06 (01) ◽  
pp. 1350003 ◽  
Author(s):  
QINYUAN GUO ◽  
SHENGLIN LUO ◽  
QINGRONG QI ◽  
CHUNMENG SHI

Our research has identified a couple of near-infrared (NIR) heptamethine indocyanine dyes exhibiting preferential tumor accumulation property for in vivo imaging. On the basis of our foregoing work, we describe here a preliminary structure–activity relationship (SAR) study of 11 related heptamethine indocyanine dyes and several essential requirements of these structures for in vivo tumor-targeted imaging.


RSC Advances ◽  
2015 ◽  
Vol 5 (79) ◽  
pp. 64076-64082 ◽  
Author(s):  
Yang Zhao ◽  
Jing Peng ◽  
Yuanjie Niu ◽  
Xuening Zhang ◽  
Ning Jiang ◽  
...  

Intravenous injection of Tf-Au NCs could be applied in the targeted imaging and early diagnosis of prostate cancer in vivo.


2021 ◽  
Vol 9 (11) ◽  
pp. e003036
Author(s):  
Shunichi Taki ◽  
Kohei Matsuoka ◽  
Yuko Nishinaga ◽  
Kazuomi Takahashi ◽  
Hirotoshi Yasui ◽  
...  

BackgroundNear-infrared photoimmunotherapy (NIR-PIT) is a new modality for treating cancer, which uses antibody-photoabsorber (IRDye700DX) conjugates that specifically bind to target tumor cells. This conjugate is then photoactivated by NIR light, inducing rapid necrotic cell death. NIR-PIT needs a highly expressed targeting antigen on the cells because of its reliance on antibodies. However, using antibodies limits this useful technology to only those patients whose tumors express high levels of a specific antigen. Thus, to propose an alternative strategy, we modified this phototechnology to augment the anticancer immune system by targeting the almost low-expressed immune checkpoint molecules on tumor cells.MethodsWe used programmed death-ligand 1 (PD-L1), an immune checkpoint molecule, as the target for NIR-PIT. Although the expression of PD-L1 on tumor cells is usually low, PD-L1 is almost expressed on tumor cells. Intratumoral depletion with PD-L1-targeted NIR-PIT was tested in mouse syngeneic tumor models.ResultsAlthough PD-L1-targeted NIR-PIT showed limited effect on tumor cells in vitro, the therapy induced sufficient antitumor effects in vivo, which were thought to be mediated by the ‘photoimmuno’ effect and antitumor immunity augmentation. Moreover, PD-L1-targeted NIR-PIT induced antitumor effect on non-NIR light-irradiated tumors.ConclusionsLocal PD-L1-targeted NIR-PIT enhanced the antitumor immune reaction through a direct photonecrotic effect, thereby providing an alternative approach to targeted cancer immunotherapy and expanding the scope of cancer therapeutics.


2020 ◽  
Author(s):  
Guanchen Zhu ◽  
Kaikai Wang ◽  
Haixiang Qin ◽  
Xiaozhi Zhao ◽  
Wei Chen ◽  
...  

Abstract Chemotherapy is a standard cancer treatment which uses anti-cancer drugs to destroy or slow the growth of cancer cells. However, chemotherapy has limited therapeutic effects in bladder cancer. One of the reasons of this resistance to chemotherapy is that higher levels of glutathione in invasive bladder cancer cells. We have fabricated nanoparticles that respond to high concentrations of glutathione and near-infrared laser irradiation in order to increase the drug accumulation at the tumor sites and combine chemotherapy with photothermal therapy to overcome the challenges of bladder cancer treatment.Methods:The DOX&IR780@PEG-PCL-SS NPs were prepared by co-precipitation method. We investigated the tumor targeting capability of NPs in vitro and in vivo. The orthotopic bladder cancer model in C57BL/6 mice was established for in vivo study and the photothermal effects and therapeutic efficacy of NPs were evaluated.Results:The DOX&IR780@PEG-PCL-SS NPs were synthesized using internal cross-linking strategy to increase the stability of nanoparticles. Nanoparticles can be ingested by tumor cells in a short time. The DOX&IR780@PEG-PCL-SS NPs have dual sensitivity to high levels of glutathione in bladder cancer cells and near-infrared laser irradiation. Glutathione triggers chemical structural changes of nanoparticles and preliminarily releases drugs, Near-infrared laser irradiation can promote the complete release of the drugs from the nanoparticles and induce a photothermal effect, leading to destroying the tumor cells. Given the excellent tumor-targeting ability and negligible toxicity to normal tissue, DOX&IR780@PEG-PCL-SS NPs can greatly increase the concentration of the anti-cancer drugs in tumor cells. The mice treated with DOX&IR780@PEG-PCL-SS NPs have a significant reduction in tumor volume. The DOX&IR780@PEG-PCL-SS NPs can be tracked by in vivo imaging system and have good tumor targeting ability, to facilitate our assessment during the experiment.Conclusion:A nanoparticle delivery system with dual sensitivity to glutathione and near-infrared laser irradiation was developed for delivering IR780 and DOX. Chemo-photothermal synergistic therapy of both primary bladder cancer and their metastases was achieved using this advanced delivery system.


2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Yingying Zhang ◽  
Yongxue Zhang ◽  
Lianglan Yin ◽  
Xiaotian Xia ◽  
Fan Hu ◽  
...  

Introduction.Radiolabeled gold nanoparticles play an important role in biomedical application. The aim of this study was to prepare iodine-131 (131I)-labeled gold nanorods (GNRs) conjugated with cyclic RGD and evaluate its biological characteristics for targeted imaging of integrinαvβ3-expressing tumors.Methods.HS-PEG(5000)-COOH molecules were applied to replace CTAB covering the surface of bare GNRs for better biocompatibility, and c(RGDfK) peptides were conjugated onto the carboxyl terminal of GNR-PEG-COOH via EDC/NHS coupling reactions. The nanoconjugate was characterized, and131I was directly tagged on the surface of GNRs via AuI bonds for SPECT/CT imaging. We preliminarily studied the characteristics of the probe and its feasibility for tumor-targeting SPECT/CT imaging.Results.The[131I]GNR-PEG-cRGD probe was prepared in a simple and rapid manner and was stable in both PBS and fetal bovine serum. It targeted selectively and could be taken up by tumor cells mainly via integrinαvβ3-receptor-mediated endocytosis. In vivo imaging, biodistribution, and autoradiography results showed evident tumor uptake in integrinαvβ3-expressing tumors.Conclusions.These promising results showed that this smart nanoprobe can be used for angiogenesis-targeted SPECT/CT imaging. Furthermore, the nanoprobe possesses a remarkable capacity for highly efficient photothermal conversion in the near-infrared region, suggesting its potential as a multifunctional theranostic agent.


2020 ◽  
Author(s):  
Guanchen Zhu ◽  
Kaikai Wang ◽  
Haixiang Qin ◽  
Xiaozhi Zhao ◽  
Wei Chen ◽  
...  

Abstract Chemotherapy is an emerging effective treatment for cancer. However, one of the reasons why chemotherapy has a limited therapeutic effect in bladder cancer is that higher levels of glutathione in invasive bladder cancer cells. We have fabricated nanoparticles that sensitive to high concentrations of glutathione and near-infrared laser irradiation, which increases the drug accumulation at the tumor site and combines chemotherapy with photothermal therapy to overcome the challenges of bladder cancer treatment.Methods: The DOX&IR780@PEG-PCL-SS NPs were prepared by co-precipitation method. We investigated the tumor targeting of NPs in vitro and in vivo. The orthotopic bladder cancer model in C57BL/6 mice was established for in vivo study and photothermal effect of NPs were demonstrated. Therapeutic efficacy of NPs for bladder cancer was evaluated.Results: The DOX&IR780@PEG-PCL-SS NPs we synthesized use internal cross-linking strategy to increase the stability of nanoparticles. Nanoparticles can be ingested by tumor cells in a short time. The DOX&IR780@PEG-PCL-SS NPs have dual sensitivity to high levels of glutathione in bladder cancer cells and near-infrared laser irradiation. Glutathione triggers chemical structural changes in nanoparticles and preliminarily releases drugs, Near-infrared laser irradiation can promote the complete release of the drug from the nanoparticles, producing a photothermal effect and further killing the tumor cells. Given the excellent tumor-targeting ability and negligible toxicity, DOX&IR780@PEG-PCL-SS NPs can greatly increase the concentration of drugs in tumor cells. The mice in the experimental group can be found to have a significant reduction in tumor volume. The DOX&IR780@PEG-PCL-SS NPs can be tracked by small animal imaging and have good imaging results, to facilitate our assessment during the experiment.Conclusion: A dual sensitivity to glutathione and near-infrared laser irradiation. Long-circulating nanoparticle was developed for delivering IR780 and DOX, which could achieve NIR laser-controlled drug release and imaging guidance for chemo-photothermal synergistic therapy of both primary bladder cancer and their metastases.


ACS Nano ◽  
2019 ◽  
Vol 13 (3) ◽  
pp. 3125-3131 ◽  
Author(s):  
Thomas Pons ◽  
Sophie Bouccara ◽  
Vincent Loriette ◽  
Nicolas Lequeux ◽  
Sophie Pezet ◽  
...  

2006 ◽  
Vol 2006 ◽  
pp. 1-7 ◽  
Author(s):  
Abu-Bakr Al-Mehdi ◽  
Mita Patel ◽  
Abu Haroon ◽  
Darla Reed ◽  
B. Ohlsson-Wilhelm ◽  
...  

Scattering of shorter-wavelength visible light limits the fluorescence imaging depth of thick specimens such as whole organs. In this study, we report the use of four newly synthesized near-infrared and far-red fluorescence probes (excitation/emission, in nm: 644/670; 683/707; 786/814; 824/834) to image tumor cells in the subpleural vasculature of the intact rat lungs. Transpelural imaging of tumor cells labeled with long-wavelength probes and expressing green fluorescent protein (GFP; excitation/emission 488/507 nm) was done in the intact rat lung after perfusate administration or intravenous injection. Our results show that the average optimum imaging depth for the long-wavelength probes is higher (27.8±0.7 μm) than for GFP (20±0.5 μm;p=0.008;n=50), corresponding to a40%increase in the volume of tissue accessible for high-resolution imaging. The maximum depth of cell visualization was significantly improved with the novel dyes (36.4±1 μm from the pleural surface) compared with GFP (30.1±0.5 μm;p=0.01;n=50). Stable binding of the long-wavelength vital dyes to the plasma membrane also permitted in vivo tracking of injected tumor cells in the pulmonary vasculature. These probes offer a significant improvement in the imaging quality of in situ biological processes in the deeper regions of intact lungs.


2019 ◽  
Vol 25 (13) ◽  
pp. 1477-1489 ◽  
Author(s):  
Valeria De Matteis ◽  
Mariafrancesca Cascione ◽  
Chiara C. Toma ◽  
Rosaria Rinaldi

The current strategies to treat different kinds of cancer are mainly based on chemotherapy, surgery and radiation therapy. Unfortunately, these approaches are not specific and rather invasive as well. In this scenario, metal nano-shells, in particular gold-based nanoshells, offer interesting perspectives in the effort to counteract tumor cells, due to their unique ability to tune Surface Plasmon Resonance in different light-absorbing ranges. In particular, the Visible and Near Infrared Regions of the electromagnetic spectrum are able to penetrate through tissues. In this way, the light absorbed by the gold nanoshell at a specific wavelength is converted into heat, inducing photothermal ablation in treated cancer cells. Furthermore, inert gold shells can be easily functionalized with different types of molecules in order to bind cellular targets in a selective manner. This review summarizes the current state-of-art of nanosystems embodying gold shells, regarding methods of synthesis, bio-conjugations, bio-distribution, imaging and photothermal effects (in vitro and in vivo), providing new insights for the development of multifunctional antitumor drugs.


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