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      1. Author :
        Valdivia, Y. Alvarado M.; Wong, K.; Cheng He, T.; Xue, Z.; Wong, S. T.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        J Vasc Interv Radiol
      6. Products :
      7. Volume :
        22
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IntegriSense, Animals; Cell Line, Tumor; Fiber Optic Technology/*methods; Fluorescent Dyes/*administration & dosage/*diagnostic use; Humans; Injections, Intralesional; Lung Neoplasms/*pathology; Microscopy, Fluorescence/*methods; Molecular Imaging/*methods; Rabbits; Surgery, Computer-Assisted/*methods; Tomography, X-Ray Computed/methods
      12. Abstract :
        PURPOSE: To show the feasibility of computed tomography (CT) image-guided fiberoptic confocal fluorescence molecular imaging in a rabbit lung tumor model. MATERIALS AND METHODS: Eight lung tumor models were created by injection of a VX2 cell suspension. The fluorescent imaging agent IntegriSense 680 was given to the animals 3.5-4 hours before the procedure. CT images were obtained and transferred to the minimally invasive multimodality image-guided (MIMIG) system as a guidance map. A real-time electromagnetically tracked needle was inserted under the visual guidance of the MIMIG system. A second CT image was obtained to confirm the location of the needle tip. Next, fiberoptic fluorescence imaging was acquired along the needle track. Finally, tumor samples were obtained for histopathologic confirmation. RESULTS: All cases were performed during breath-hold. Tumor size was 12.5 mm +/- 1.6; the distance from the chest wall was 2.1 mm +/- 0.5. The needle tip reached the tumor in all cases with an accuracy of 3.3 mm +/- 1.6. Only one skin entry point was necessary, and no needle adjustments were required. No pneumothorax was observed. At least two-fold alpha(v)beta(3) integrin image contrast was detected in the tumor compared with normal lung tissue. Tumor samples were confirmed to have viable VX2 cells and contrast uptake. CONCLUSIONS: The MIMIG system enables effective in situ fluorescence molecular imaging in a needle biopsy lung procedure. In situ alpha(v)beta(3) integrin molecular imaging allows molecular characterization of lung tumors at multiple regions and can be used to guide biopsy procedures.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22019854
      14. Call Number :
        PKI @ kd.modi @ 14
      15. Serial :
        10383
      1. Author :
        Hutteman, M.; Mieog, J. S.; van der Vorst, J. R.; Dijkstra, J.; Kuppen, P. J.; van der Laan, A. M.; Tanke, H. J.; Kaijzel, E. L.; Que, I.; van de Velde, C. J.; Lowik, C. W.; Vahrmeijer, A. L.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Eur J Surg Oncol
      6. Products :
      7. Volume :
        37
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IntegriSense, Animals; Colorectal Neoplasms/*metabolism/*secondary; Disease Models, Animal; Image Processing, Computer-Assisted; Integrin alphaVbeta3/*metabolism; Intraoperative Period; Liver Neoplasms/*pathology; Male; Neoplasm Transplantation; Rats; Spectroscopy, Near-Infrared/*methods; Tumor Cells, Cultured
      12. Abstract :
        AIM: Near-infrared (NIR) fluorescence optical imaging is a promising technique to assess the extent of colorectal metastases during curative-intended surgery. However, NIR fluorescence imaging of liver metastases is highly challenging due to hepatic uptake and clearance of many fluorescent dyes. In the current study, the biodistribution and the ability to demarcate liver and peritoneal metastases were assessed during surgery in a syngeneic rat model of colorectal cancer using an integrin alpha(v)beta(3)-directed NIR fluorescence probe. METHODS: Liver tumors and peritoneal metastases were induced in 7 male WAG/Rij rats by subcapsular inoculation of 0.5 x 10(6) CC531 colorectal cancer rat cells into three distinct liver lobes. Intraoperative and ex vivo fluorescence measurements were performed 24 (N = 3 rats, 7 tumors) and 48 h (N = 4 rats, 9 tumors) after intravenous administration of the integrin alpha(v)beta(3)-directed NIR fluorescence probe. RESULTS: Colorectal metastases had a minimal two-fold higher NIR fluorescence signal than healthy liver tissue and other abdominal organs (p < 0.001). The tumor-to-background ratio was independent of time of imaging (24 h vs. 48 h post-injection; p = 0.31), which facilitates flexible operation planning in future clinical applications. Total fluorescence intensity was significantly correlated with the size of metastases (R(2) = 0.92 for the 24 h group, R(2) = 0.96 for the 48 h group). CONCLUSION: These results demonstrate that colorectal intra-abdominal metastases can be clearly demarcated during surgery using an integrin alpha(v)beta(3) targeting NIR fluorescence probe. Translating these findings to the clinic will have an excellent potential to substantially improve the quality of cancer surgery.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21215590
      14. Call Number :
        PKI @ kd.modi @ 23
      15. Serial :
        10366
      1. Author :
        Nahrendorf, M.; Keliher, E.; Marinelli, B.; Waterman, P.; Feruglio, P. F.; Fexon, L.; Pivovarov, M.; Swirski, F. K.; Pittet, M. J.; Vinegoni, C.; Weissleder, R.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Proc Natl Acad Sci U S A
      6. Products :
      7. Volume :
        107
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IntegriSense, Animals; Flow Cytometry; Fluorescent Dyes/*diagnostic use; Image Processing, Computer-Assisted/methods; Mice; Mice, Inbred C57BL; Nanoparticles/*diagnostic use; Neoplasms/*diagnosis; Positron-Emission Tomography/*methods; Tomography, X-Ray Computed/*methods
      12. Abstract :
        Fusion imaging of radionuclide-based molecular (PET) and structural data [x-ray computed tomography (CT)] has been firmly established. Here we show that optical measurements [fluorescence-mediated tomography (FMT)] show exquisite congruence to radionuclide measurements and that information can be seamlessly integrated and visualized. Using biocompatible nanoparticles as a generic platform (containing a (18)F isotope and a far red fluorochrome), we show good correlations between FMT and PET in probe concentration (r(2) > 0.99) and spatial signal distribution (r(2) > 0.85). Using a mouse model of cancer and different imaging probes to measure tumoral proteases, macrophage content and integrin expression simultaneously, we demonstrate the distinct tumoral locations of probes in multiple channels in vivo. The findings also suggest that FMT can serve as a surrogate modality for the screening and development of radionuclide-based imaging agents.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20385821
      14. Call Number :
        PKI @ kd.modi @ 21
      15. Serial :
        10375
      1. Author :
        Snoeks, T. J.; Lowik, C. W.; Kaijzel, E. L.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Angiogenesis
      6. Products :
      7. Volume :
        13
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IntegriSense,, Animals; Diagnostic Imaging/*methods; Fluorescent Dyes/metabolism; Genes, Reporter; Neovascularization, Pathologic/*diagnosis; *Optical Phenomena
      12. Abstract :
        In recent years, molecular imaging gained significant importance in biomedical research. Optical imaging developed into a modality which enables the visualization and quantification of all kinds of cellular processes and cancerous cell growth in small animals. Novel gene reporter mice and cell lines and the development of targeted and cleavable fluorescent “smart” probes form a powerful imaging toolbox. The development of systems collecting tomographic bioluminescence and fluorescence data enabled even more spatial accuracy and more quantitative measurements. Here we describe various bioluminescent and fluorescent gene reporter models and probes that can be used to specifically image and quantify neovascularization or the angiogenic process itself.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20449766
      14. Call Number :
        PKI @ kd.modi @ 10
      15. Serial :
        10379
      1. Author :
        Keereweer, S.; Kerrebijn, J. D.; van Driel, P. B.; Xie, B.; Kaijzel, E. L.; Snoeks, T. J.; Que, I.; Hutteman, M.; van der Vorst, J. R.; Mieog, J. S.; Vahrmeijer, A. L.; van de Velde, C. J.; Baatenburg de Jong, R. J.; Lowik, C. W.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Mol Imaging Biol
      6. Products :
      7. Volume :
        13
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IntegriSense,Animals; Fluorescent Dyes/metabolism; Humans; Nanoparticles/diagnostic use; Optics and Photonics/*methods; Surgery, Computer-Assisted/*methods
      12. Abstract :
        In cancer surgery, intra-operative assessment of the tumor-free margin, which is critical for the prognosis of the patient, relies on the visual appearance and palpation of the tumor. Optical imaging techniques provide real-time visualization of the tumor, warranting intra-operative image-guided surgery. Within this field, imaging in the near-infrared light spectrum offers two essential advantages: increased tissue penetration of light and an increased signal-to-background-ratio of contrast agents. In this article, we review the various techniques, contrast agents, and camera systems that are currently used for image-guided surgery. Furthermore, we provide an overview of the wide range of molecular contrast agents targeting specific hallmarks of cancer and we describe perspectives on its future use in cancer surgery.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20617389
      14. Call Number :
        PKI @ kd.modi @ 4
      15. Serial :
        10367
      1. Author :
        Strasky, Zbynek; Zemankova, Lenka; Nemeckova, Ivana; Rathouska, Jana; Wong, Ronald J; Muchova, Lucie; Subhanova, Iva; Vanikova, Jana; Vanova, Katerina; Vitek, Libor
      2. Title :
        Spirulina platensis and phycocyanobilin activate atheroprotective heme oxygenase-1: A possible implication for atherogenesis
      3. Type :
        Journal Article
      4. Year :
        2013
      5. Publication :
        Food Funct.
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS Imaging
      12. Abstract :
        Spirulina platensis, a water blue-green alga, has been associated with potent biological effects, which might have important relevance in atheroprotection. We investigated whether S. platensis or phycocyanobilin (PCB), its tetrapyrrolic chromophore, can activate atheroprotective heme oxygenase-1 (Hmox1), a key enzyme in the heme catabolic pathway responsible for generation of a potent antioxidant bilirubin, in endothelial cells and in a mouse model of atherosclerosis. In vitro experiments were performed on EA.hy926 endothelial cells exposed to extracts of S. platensis or PCB. In vivo studies were performed on ApoE-deficient mice fed a cholesterol diet and S. platensis. The effect of these treatments on Hmox1, as well as other markers of oxidative stress and endothelial dysfunction, was then investigated. Both S. platensis and PCB markedly upregulated Hmox1 in vitro, and a substantial overexpression of Hmox1 was found in aortic atherosclerotic lesions of ApoE-deficient mice fed S. platensis. In addition, S. platensis treatment led to a significant increase in Hmox1 promoter activity in the spleens of Hmox-luc transgenic mice. Furthermore, both S. platensis and PCB were able to modulate important markers of oxidative stress and endothelial dysfunction, such as eNOS, p22 NADPH oxidase subunit, and/or VCAM-1. Both S. platensis and PCB activate atheroprotective HMOX1 in endothelial cells and S. platensis increased the expression of Hmox1 in aortic atherosclerotic lesions in ApoE-deficient mice, and also in Hmox-luc transgenic mice beyond the lipid lowering effect. Therefore, activation of HMOX1 and the heme catabolic pathway may represent an important mechanism of this food supplement for the reduction of atherosclerotic disease.
      13. URL :
        N/A
      14. Call Number :
        PKI @ catherine.lautenschlager @ 6049
      15. Serial :
        14630
      1. Author :
        Zhou, H.; Roy, S.; Cochran, E.; Zouaoui, R.; Chu, C. L.; Duffner, J.; Zhao, G.; Smith, S.; Galcheva-Gargova, Z.; Karlgren, J.; Dussault, N.; Kwan, R. Y.; Moy, E.; Barnes, M.; Long, A.; Honan, C.; Qi, Y. W.; Shriver, Z.; Ganguly, T.; Schultes, B.; Venkataraman, G.; Kishimoto, T. K.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        PLoS One
      6. Products :
      7. Volume :
        6
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, 4T1-luc2
      12. Abstract :
        Heparan sulfate proteoglycans (HSPGs) play a key role in shaping the tumor microenvironment by presenting growth factors, cytokines, and other soluble factors that are critical for host cell recruitment and activation, as well as promoting tumor progression, metastasis, and survival. M402 is a rationally engineered, non-cytotoxic heparan sulfate (HS) mimetic, designed to inhibit multiple factors implicated in tumor-host cell interactions, including VEGF, FGF2, SDF-1alpha, P-selectin, and heparanase. A single s.c. dose of M402 effectively inhibited seeding of B16F10 murine melanoma cells to the lung in an experimental metastasis model. Fluorescent-labeled M402 demonstrated selective accumulation in the primary tumor. Immunohistological analyses of the primary tumor revealed a decrease in microvessel density in M402 treated animals, suggesting anti-angiogenesis to be one of the mechanisms involved in-vivo. M402 treatment also normalized circulating levels of myeloid derived suppressor cells in tumor bearing mice. Chronic administration of M402, alone or in combination with cisplatin or docetaxel, inhibited spontaneous metastasis and prolonged survival in an orthotopic 4T1 murine mammary carcinoma model. These data demonstrate that modulating HSPG biology represents a novel approach to target multiple factors involved in tumor progression and metastasis.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21698156
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10362
      1. Author :
        Carlisle, R.; Seymour, L. W.; Coussios, C. C.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Pharm Res
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, B16-F10-luc-G5, B16F10-luc-G5, B16-F10-luc, B16F10-luc
      12. Abstract :
        PURPOSE: To improve the delivery of liposomes to tumors using P-selectin glycoprotein ligand 1 (PSGL1) mediated binding to selectin molecules, which are upregulated on tumorassociated endothelium. METHODS: PSGL1 was orientated and presented on the surface of liposomes to achieve optimal selectin binding using a novel streptavidin-protein G linker molecule. Loading of PSGL1 liposomes with luciferin allowed their binding to e-selectin and activated HUVEC to be quantified in vitro and their stability, pharmacokinetics and tumor accumulation to be tested in vivo using murine models. RESULTS: PSGL1 liposomes showed 5-fold (p < 0.05) greater selectin binding than identically formulated control liposomes modified with ligand that did not contain the selectin binding domain. When added to HUVEC, PSGL1 liposomes showed >7-fold (p < 0.001) greater attachment than control liposomes. In in vivo studies PSGL1 liposomes showed similar stability and circulation to control liposomes but demonstrated a >3-fold enhancement in the level of delivery to tumors (p < 0.05). CONCLUSIONS: The technologies and strategies described here may contribute to clinical improvements in the selectivity and efficacy of liposomal drug delivery agents.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22992830
      14. Call Number :
        PKI @ kd.modi @ 19
      15. Serial :
        10529
      1. Author :
        Lemarie, F.; Chang, C. W.; Blatchford, D. R.; Amor, R.; Norris, G.; Tetley, L.; McConnell, G.; Dufes, C.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Nanomedicine (Lond)
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, B16-F10-luc-G5, B16F10-luc-G5, B16-F10-luc, B16F10-luc
      12. Abstract :
        Aim: The therapeutic potential of epigallocatechin-3-gallate (EGCG), a green tea polyphenol with anticancer properties, is limited by its inability to specifically reach tumors following intravenous administration. The purpose of this study was to determine whether a tumor-targeted vesicular formulation of EGCG would suppress the growth of A431 epidermoid carcinoma and B16-F10 melanoma in vitro and in vivo. Materials & methods: Transferrin-bearing vesicles encapsulating EGCG were administered intravenously to mice bearing subcutaneous A431 and B16-F10 tumors. Results: The intravenous administration of EGCG encapsulated in transferrin-bearing vesicles resulted in tumor suppression in 40% of A431 and B16-F10 tumors. Animal survival was improved by more than 20 days compared with controls. Conclusion: Encapsulation of EGCG in transferrin-bearing vesicles is a promising therapeutic strategy. Original submitted 28 November 2011; Revised submitted 11 May 2012.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22891867
      14. Call Number :
        PKI @ kd.modi @ 14
      15. Serial :
        10532