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      1. Author :
        Christoph Bremer; Ching-Hsuan Tung; Ralph Weissleder
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2001
      5. Publication :
        Nature Medicine
      6. Products :
      7. Volume :
        7
      8. Issue :
        6
      9. Page Numbers :
        N/A
      10. Research Area :
        Cancer
      11. Keywords :
        near-infrared; near infrared; matrix metalloproteinase; MMP; in vivo imaging; near-infrared fluorescence imaging
      12. Abstract :
        A number of different matrix metalloproteinase (MMP) inhibitors have been developed as cytostatic and anti-angiogenic agents and are currently in clinical testing. One major hurdle in assessing the efficacy of such drugs has been the inability to sense or image anti-proteinase activity directly and non-invasively in vivo. We show here that novel, biocompatible near-infrared fluorogenic MMP substrates can be used as activatable reporter probes to sense MMP activity in intact tumors in nude mice. Moreover, we show for the first time that the effect of MMP inhibition can be directly imaged using this approach within hours after initiation of treatment using the potent MMP inhibitor, prinomastat (AG3340). The developed probes, together with novel near-infrared fluorescence imaging technology will enable the detailed analysis of a number of proteinases critical for advancing the therapeutic use of clinical proteinase inhibitors.
      13. URL :
        http://www.nature.com/nm/journal/v7/n6/abs/nm0601_743.html
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4509
      1. Author :
        N/A
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Molecular Imaging and Biology
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        Cancer
      11. Keywords :
        Optical imaging, Image-guided surgery, Molecular imaging, Near-infrared fluorescence
      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-tobackground-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.springerlink.com/content/78233815221t6563/
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4486
      1. Author :
        Jeffrey D Peterson; Timothy P LaBranche; Kristine O Vasquez; Sylvie Kossodo; Michele Melton; Randall Rader; John T Listello; Mark A Abrams; Thomas P Misko
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Arthritis Research & Therapy
      6. Products :
      7. Volume :
        12
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        optical tomography; in vivo imaging; inflammation; Fluorescence molecular tomographic; FMT
      12. Abstract :
        Introduction: Standard measurements used to assess murine models of rheumatoid arthritis, notably paw thickness and clinical score, do not align well with certain aspects of disease severity as assessed by histopathology. We tested the hypothesis that non-invasive optical tomographic imaging of molecular biomarkers of inflammation and bone turnover would provide a superior quantitative readout and would discriminate between a disease-modifying anti-rheumatic drug (DMARD) and a non-DMARD treatment.

        Methods: Using two protease-activated near-infrared fluorescence imaging agents to detect inflammation-associated cathepsin and matrix metalloprotease activity, and a third agent to detect bone turnover, we quantified fluorescence in paws of mice with collagen antibody-induced arthritis. Fluorescence molecular tomographic (FMT) imaging results, which provided deep tissue detection and quantitative readouts in absolute picomoles of agent fluorescence per paw, were compared with paw swelling, clinical scores, a panel of plasma biomarkers, and histopathology to discriminate between steroid (prednisolone), DMARD (p38 mitogen-activated protein kinase (MAPK) inhibitor) and non-DMARD (celecoxib, cyclooxygenase-2 (COX-2) inhibitor) treatments.

        Results: Paw thickness, clinical score, and plasma biomarkers failed to discriminate well between a p38 MAPK inhibitor and a COX-2 inhibitor. In contrast, FMT quantification using near-infrared agents to detect protease activity or bone resorption yielded a clear discrimination between the different classes of therapeutics. FMT results agreed well with inflammation scores, and both imaging and histopathology provided clearer discrimination between treatments as compared with paw swelling, clinical score, and serum biomarker readouts.

        Conclusions: Non-invasive optical tomographic imaging offers a unique approach to monitoring disease pathogenesis and correlates with histopathology assessment of joint inflammation and bone resorption. The specific use of optical tomography allowed accurate three-dimensional imaging, quantitation in picomoles rather than intensity or relative fluorescence, and, for the first time, showed that non-invasive imaging assessment can predict the pathologist's histology inflammation scoring and discriminate DMARD from non-DMARD activity.
      13. URL :
        http://arthritis-research.com/content/12/3/R105
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4513
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