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      1. Author :
        Hidemi Hattori, Kaori Higuchi, Yashiro Nogami, Yoshiko Amano, Masayuki Ishihara and Bonpei Takase
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Circulation: Cardiovascular Imaging
      6. Products :
      7. Volume :
        2
      8. Issue :
        3
      9. Page Numbers :
        N/A
      10. Research Area :
        Cardiovascular Research
      11. Keywords :
        In vivo imaging; AngioSense
      12. Abstract :
        Extract:

        With the advent of tissue regeneration and gene therapy for heart disease, evaluation of coronary circulation and cardiac function in vivo, especially in a disease model, is extremely important. Conventional methods such as microcomputed tomography, high-resolution magnetic resonance angiography, and high-resolution ultrasound have become invaluable tools in cardiovascular research. However, the disadvantages and limitations of these approaches sometimes preclude researchers from conducting important and specific studies on coronary circulation and cardiac function. Therefore, we developed and applied a novel real-time, in vivo fluorescent optical imaging system for use in the mouse cardiovascular system. We report the use of this system for repeatedly assessing coronary circulation, cardiovascular structure, and cardiac function in live mice...
      13. URL :
        http://circimaging.ahajournals.org/content/2/3/277.extract
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4648
      1. Author :
        Napp, J.; Mathejczyk, J.E.; Alves, F.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Pediatric Radiology
      6. Products :
      7. Volume :
        41
      8. Issue :
        2
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        AngioSense 680; Cancer; glioblastoma xenograft; mice; tumor vascularization
      12. Abstract :
        To obtain information on the occurrence and location of molecular events as well as to track target-specific probes such as antibodies or peptides, drugs or even cells non-invasively over time, optical imaging (OI) technologies are increasingly applied. Although OI strongly contributes to the advances made in preclinical research, it is so far, with the exception of optical coherence tomography (OCT), only very sparingly applied in clinical settings. Nevertheless, as OI technologies evolve and improve continuously and represent relatively inexpensive and harmful methods, their implementation as clinical tools for the assessment of children disease is increasing. This review focuses on the current preclinical and clinical applications as well as on the future potential of OI in the clinical routine. Herein, we summarize the development of different fluorescence and bioluminescence imaging techniques for microscopic and macroscopic visualization of microstructures and biological processes. In addition, we discuss advantages and limitations of optical probes with distinct mechanisms of target-detection as well as of different bioluminescent reporter systems. Particular attention has been given to the use of near-infrared (NIR) fluorescent probes enabling observation of molecular events in deeper tissue.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21221568
      14. Call Number :
        PKI @ user @ 8559
      15. Serial :
        4796
      1. Author :
        Ackermann, M.; Carvajal, I.M.; Morse, B.A.; Moreta, M.; O'Neil, S.; Kossodo, S.; Peterson, J.D.; Delventhal, V.; Marsh, H.N.; Furfine, E.S.; Konerding, M.A.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        International Journal of Oncology
      6. Products :
      7. Volume :
        38
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        AngioSense 680; anti-angiogenic; anti-tumorigenic; Cancer; FMT1 (VisEn); FMT-Solaris; In vivo imaging (VisEn); intraperitoneal injection; mice
      12. Abstract :
        Antiangiogenesis has become a promising pillar in modern cancer therapy. This study investigates the antiangiogenic effects of the PEGylated Adnectin[TM], CT-322, in a murine Colo-205 xenograft tumor model. CT-322 specifically binds to and blocks vascular endothelial growth factor receptor (VEGFR-2). Adnectins are a novel class of targeted biologics engineered from the 10th domain of human fibronectin. CT-322 treated tumors exhibited a significant reduction in tumor growth of 69%, a 2.8 times lower tumor surface area and fewer necrotic areas. Control tumors showed a 2.36-fold higher microvessel density (MVD) and a 2.42 times higher vessel volume in corrosion casts. The vascular architecture in CT-322-treated tumors was characterized by a strong normalization of vasculature. This was quantified in corrosion casts of CT-322 treated tumors in which the intervascular distance (a reciprocal parameter indicative of vessel density) and the distance between two consecutive branchings were assessed, with these distances being 2.21 times and 2.37 times greater than in controls, respectively. Fluorescence molecular tomography (FMT) equally affirmed the inhibitory effects of CT-322 on tumor vasculature as indicated by a 60% reduction of the vascular probe, AngioSense, accumulating in tumor tissue, as a measurement of vascular permeability. Moreover, AngioSense accumulation was reduced as early as 24 h after starting treatment. The sum of these effects on tumor vasculature illustrates the anti-angiogenic mechanism underlying the antitumor activity of CT-322 and provides support for further evaluation of this Adnectin in combinatorial strategies with standard of care therapies.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21109927
      14. Call Number :
        PKI @ user @ 8449
      15. Serial :
        4804
      1. Author :
        Earley, S.; Vinegoni, C.; Dunham, J.; Gorbatov, R.; Feruglio, P. F.; Weissleder, R.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Cancer Res
      6. Products :
      7. Volume :
        72
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        AngioSense, Annexin Vivo, Annexin-Vivo, Aniline Compounds/*pharmacology; Animals; Antineoplastic Agents/*pharmacology; *Apoptosis; Breast Neoplasms/drug therapy/*physiopathology; Cell Line, Tumor; Female; Green Fluorescent Proteins; Humans; Image Processing, Computer-Assisted; Mice; Mice, Nude; Mitochondrial Membranes/drug effects/*physiology; Mitochondrial Proteins/metabolism; Molecular Imaging/*methods; Pancreatic Neoplasms/drug therapy/*physiopathology; Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors; Recombinant Fusion Proteins/metabolism; Single-Cell Analysis; Sulfonamides/*pharmacology; Tumor Microenvironment
      12. Abstract :
        Observing drug responses in the tumor microenvironment in vivo can be technically challenging. As a result, cellular responses to molecularly targeted cancer drugs are often studied in cell culture, which does not accurately represent the behavior of cancer cells growing in vivo. Using high-resolution microscopy and fluorescently labeled genetic reporters for apoptosis, we developed an approach to visualize drug-induced cell death at single-cell resolution in vivo. Stable expression of the mitochondrial intermembrane protein IMS-RP was established in human breast and pancreatic cancer cells. Image analysis was then used to quantify release of IMS-RP into the cytoplasm upon apoptosis and irreversible mitochondrial permeabilization. Both breast and pancreatic cancer cells showed higher basal apoptotic rates in vivo than in culture. To study drug-induced apoptosis, we exposed tumor cells to navitoclax (ABT-263), an inhibitor of Bcl-2, Bcl-xL, and Bcl-w, both in vitro and in vivo. Although the tumors responded to Bcl-2 inhibition in vivo, inducing apoptosis in around 20% of cancer cells, the observed response was much higher in cell culture. Together, our findings show an imaging technique that can be used to directly visualize cell death within the tumor microenvironment in response to drug treatment.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22505651
      14. Call Number :
        PKI @ kd.modi @ 11
      15. Serial :
        10433
      1. Author :
        Stelter, L.; Tseng, J. C.; Torosjan, A.; Levin, B.; Longo, V. A.; Pillarsetty, N.; Zanzonico, P.; Meruelo, D.; Larson, S. M.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Mol Imaging Biol
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        AngioSense, FMT, IVIS, Biolumninescence
      12. Abstract :
        PURPOSE: Sindbis virus (SINV) infect tumor cells specifically and systemically throughout the body. Sindbis vectors are capable of expressing high levels of transduced suicide genes and thus efficiently produce enzymes for prodrug conversion in infected tumor cells. The ability to monitor suicide gene expression levels and viral load in patients, after administration of the vectors, would significantly enhance this tumor-specific therapeutic option. PROCEDURES: The tumor specificity of SINV is mediated by the 67-kDa laminin receptor (LR). We probed different cancer cell lines for their LR expression and, to determine the specific role of LR-expression in the infection cycle, used different molecular imaging strategies, such as bioluminescence, fluorescence molecular tomography, and positron emission tomography, to evaluate SINV-mediated infection in vitro and in vivo. RESULTS: All cancer cell lines showed a marked expression of LR. The infection rates of the SINV particles, however, differed significantly among the cell lines. CONCLUSION: We used novel molecular imaging techniques to visualize vector delivery to different neoplatic cells. SINV infection rates proofed to be not solely dependent on cellular LR expression. Further studies need to evaluate the herein discussed ways of cellular infection and viral replication.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22847302
      14. Call Number :
        PKI @ kd.modi @ 3
      15. Serial :
        10440
      1. Author :
        Tseng, J. C.; Granot, T.; DiGiacomo, V.; Levin, B.; Meruelo, D.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Cancer Gene Ther
      6. Products :
      7. Volume :
        17
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        AngioSense, IVIS, Alphavirus Infections/pathology/*therapy/virology; Animals; Antineoplastic Agents, Phytogenic/therapeutic use; Blotting, Western; Cell Membrane Permeability; Combined Modality Therapy; Cricetinae; Drug Delivery Systems; Female; *Genetic Vectors; Humans; Mice; Mice, SCID; Neovascularization, Pathologic/*prevention & control; Neuroblastoma/blood supply/therapy/virology; *Oncolytic Virotherapy; Ovarian Neoplasms/*blood supply/*therapy/virology; Paclitaxel/therapeutic use; Sindbis Virus/*physiology; Vascular Endothelial Growth Factor A/metabolism; Xenograft Model Antitumor Assays
      12. Abstract :
        Genetic instability of cancer cells generates resistance after initial responses to chemotherapeutic agents. Several oncolytic viruses have been designed to exploit specific signatures of cancer cells, such as important surface markers or pivotal signaling pathways for selective replication. It is less likely for cancer cells to develop resistance given that mutations in these cancer signatures would negatively impact tumor growth and survival. However, as oncolytic viral vectors are large particles, they suffer from inefficient extravasation from tumor blood vessels. Their ability to reach cancer cells is an important consideration in achieving specific oncolytic targeting and potential vector replication. Our previous studies indicated that the Sindbis viral vectors target tumor cells by the laminin receptor. Here, we present evidence that modulating tumor vascular leakiness, using VEGF and/or metronomic chemotherapy regimens, significantly enhances tumor vascular permeability and directly enhances oncolytic Sindbis vector targeting in tumor models. Because host-derived vascular endothelium cells are genetically stable and less likely to develop resistance to chemotherapeutics, a combined metronomic chemotherapeutics and oncolytic vector regimen should provide a new approach for cancer therapy. This mechanism could explain the synergistic treatment outcomes observed in clinical trials of combined therapies.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19798121
      14. Call Number :
        PKI @ kd.modi @ 2
      15. Serial :
        10442
      1. Author :
        Thomas Reiner, Rainer H. Kohler, Chong Wee Liew, Jonathan Hill, Jason Gaglia, Rohit Kulkarni and Ralph Weissleder
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Bioconjugate Chemistry
      6. Products :
      7. Volume :
        21
      8. Issue :
        7
      9. Page Numbers :
        N/A
      10. Research Area :
        Metabolic Disorders
      11. Keywords :
        Beta-cells; GLP1-R; imaging; targeting; in vivo imaging; VivoTag; AngioSense; Diabetes
      12. Abstract :
        The ability to image and ultimately quantitate beta-cell mass in vivo will likely have far reaching implications in the study of diabetes biology, in the monitoring of disease progression or response to treatment, as well as for drug development. Here, using animal models, we report on the synthesis, characterization of, and intravital microscopic imaging properties of a near infrared fluorescent exendin-4 analogue with specificity for the GLP-1 receptor on beta cells (E4K12-Fl). The agent demonstrated sub-nanomolar EC50 binding concentrations, with high specificity and binding could be inhibited by GLP-1R agonists. Following intravenous administration to mice, pancreatic islets were readily distinguishable from exocrine pancreas, achieving target-to-background ratios within the pancreas of 6:1, as measured by intravital microscopy. Serial imaging revealed rapid accumulation kinetics (with initial signal within the islets detectable within 3 minutes and peak fluorescence within 20 minutes of injection) making this an ideal agent for in vivo imaging.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2912453/?tool=pubmed
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4561