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      1. Author :
        Kimberly A. Kelly; Nabeel Bardeesy; Rajesh Anbazhagan; Sushma Gurumurthy; Justin Berger; Herlen Alencar; Ronald A. DePinho; Umar Mahmood; Ralph Weissleder
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2008
      5. Publication :
        PLoS Medicine
      6. Products :
      7. Volume :
        15
      8. Issue :
        5
      9. Page Numbers :
        N/A
      10. Research Area :
        Cancer; Biology
      11. Keywords :
        in vivo imaging; cancer
      12. Abstract :
        Background: Pancreatic ductal adenocarcinoma (PDAC) carries an extremely poor prognosis, typically presenting with metastasis at the time of diagnosis and exhibiting profound resistance to existing therapies. The development of molecular markers and imaging probes for incipient PDAC would enable earlier detection and guide the development of interventive therapies. Here we sought to identify novel molecular markers and to test their potential as targeted imaging agents.

        Methods and Findings: Here, a phage display approach was used in a mouse model of PDAC to screen for peptides that specifically bind to cell surface antigens on PDAC cells. These screens yielded a motif that distinguishes PDAC cells from normal pancreatic duct cells in vitro, which, upon proteomics analysis, identified plectin-1 as a novel biomarker of PDAC. To assess their utility for in vivo imaging, the plectin-1 targeted peptides (PTP) were conjugated to magnetofluorescent nanoparticles. In conjunction with intravital confocal microscopy and MRI, these nanoparticles enabled detection of small PDAC and precursor lesions in engineered mouse models.

        Conclusions: Our approach exploited a well-defined model of PDAC, enabling rapid identification and validation of PTP. The developed specific imaging probe, along with the discovery of plectin-1 as a novel biomarker, may have clinical utility in the diagnosis and management of PDAC in humans.
      13. URL :
        http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0050085
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4478
      1. Author :
        Luker, G.D.; Luker, K.E.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2008
      5. Publication :
        Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
      6. Products :
      7. Volume :
        49
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Clinical Medicine; Contrast Media; Diagnostic Imaging; Fluorescence; Image Processing, Computer-Assisted; in vivo; in vivo imaging; Luminescent Measurements; Mice; Neoplasm Metastasis; Neoplasms; Optics and Photonics; Peptide Hydrolases; Rats; Signal Transduction; Software; Tomography, Optical
      12. Abstract :
        Optical techniques, such as bioluminescence and fluorescence, are emerging as powerful new modalities for molecular imaging in disease and therapy. Combining innovative molecular biology and chemistry, researchers have developed optical methods for imaging a variety of cellular and molecular processes in vivo, including protein interactions, protein degradation, and protease activity. Whereas optical imaging has been used primarily for research in small-animal models, there are several areas in which optical molecular imaging will translate to clinical medicine. In this review, we summarize recent advances in optical techniques for molecular imaging and the potential impact for clinical medicine.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/18077528
      14. Call Number :
        PKI @ user @ 7444
      15. Serial :
        4477
      1. Author :
        G. Blum
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2008
      5. Publication :
        Current Opinion in Drug Discovery Development
      6. Products :
      7. Volume :
        10
      8. Issue :
        2
      9. Page Numbers :
        N/A
      10. Research Area :
        Biology; Cancer
      11. Keywords :
        Proteases; pathology; biological markers; fluorescence imaging reagents; in vivo imaging; fluorescence molecular tomography; FMT
      12. Abstract :
        Proteases play pivotal roles in the normal function of cells. In addition, the expression and activity of proteases are significantly upregulated in several pathologies, including cancer, arthritis and atherosclerosis, and hence they can be considered to be biological markers for these pathologies. The hydrolyzing activity of proteases has been used to generate a variety of fluorescent imaging reagents, the design and utility of which are reviewed here. The use of imaging reagents to visualize protease activity allows for improved detection of various pathologies as well as the ability to monitor the efficacy of therapies in vivo and provide molecular information regarding the nature of the pathology.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/18729022
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4475
      1. Author :
        Houari Korideck; Jeffrey D. Peterson
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Journal of Pharmacology and Experimental Therapeutics
      6. Products :
      7. Volume :
        329
      8. Issue :
        3
      9. Page Numbers :
        N/A
      10. Research Area :
        Cardiovascular Research; Biology
      11. Keywords :
        in vivo imaging; therapeutics; asthma; pulmonary diseases; noninvasive; infrared imaging; fluorescence molecular tomography; FMT; Fluorescence Imaging Agents
      12. Abstract :
        Animal models of pulmonary inflammation are critical for understanding the pathophysiology of asthma and for developing new therapies. Current conventional assessments in mouse models of asthma and chronic obstructive pulmonary disease rely on invasive measures of pulmonary function and terminal characterization of cells infiltrating into the lung. The ability to noninvasively visualize and quantify the underlying biological processes in mouse pulmonary models in vivo would provide a significant advance in characterizing disease processes and the effects of therapeutics. We report the utility of near-infrared imaging agents, in combination with fluorescence molecular tomography (FMT) imaging, for the noninvasive quantitative imaging of mouse lung inflammation in an ovalbumin (OVA)-induced chronic asthma model. BALB/c mice were intraperitoneally sensitized with OVA-Alum (aluminum hydroxide) at days 0 and 14, followed by daily intranasal challenge with OVA in phosphate-buffered saline from days 21 to 24. Dexamethasone and control therapies were given intraperitoneally 4 h before each intranasal inhalation of OVA from days 21 to 24. Twenty-four hours before imaging, the mice were injected intravenously with 5 nmol of the cathepsin-activatable fluorescent agent, ProSense 680. Quantification by FMT revealed in vivo cysteine protease activity within the lung associated with the inflammatory eosinophilia, which decreased in response to dexamethasone treatment. Results were correlated with in vitro laboratory tests (bronchoalveolar lavage cell analysis and immunohistochemistry) and revealed good correlation between these measures and quantification of ProSense 680 activation. We have demonstrated the ability of FMT to noninvasively visualize and quantify inflammation in the lung and monitor therapeutic efficacy in vivo.
      13. URL :
        http://jpet.aspetjournals.org/content/329/3/882.full
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4473
      1. Author :
        Matthias Nahrendorf; Edmund Keliher; Brett Marinelli; Peter Waterman; Paolo Fumene Feruglio; Lioubov Fexon; Misha Pivovarov; Filip K. Swirski; Mikael J. Pittet; Claudio Vinegoni; Ralph Weissleder
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        PNAS
      6. Products :
      7. Volume :
        107
      8. Issue :
        17
      9. Page Numbers :
        N/A
      10. Research Area :
        Cancer
      11. Keywords :
        fluorescence molecular tomography; FMT; Fluorescence Imaging Agents; ProSense; fluorescence-mediated tomography; molecular imaging; multimodal image fusion; computed tomography; cancer
      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 18F isotope and a far red fluorochrome), we show good correlations between FMT and PET in probe concentration (r2 > 0.99) and spatial signal distribution (r2 > 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.pnas.org/content/107/17/7910.abstract?sid=084c1ba8-0b02-4833-acdd-b57bea226faf
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4468
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