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      1. Author :
        Penna, F. J.; Freilich, D. A.; Alvarenga, C.; Nguyen, H. T.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Urology
      6. Products :
      7. Volume :
        78
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        OsteoSense, Animals; Fluorescence; Fluorescent Dyes/*diagnostic use; Guinea Pigs; Lymph Node Excision/*methods; Male; Models, Animal; *Molecular Imaging; Retroperitoneal Space
      12. Abstract :
        OBJECTIVES: To propose that fluorescent molecular imaging has utility in specifically identifying the lymph nodes, thereby enabling more definitive lymph node visualization and dissection. Retroperitoneal lymph node dissection (RPLND) is an invasive procedure with significant morbidity. A minimally invasive approach would be of great clinical benefit but has been limited by the extensive perivascular dissection required to remove all lymphatic tissue. Directed lymph node visualization would allow a limited dissection, making a laparoscopic approach more feasible. METHODS: Ten male Hartley guinea pigs underwent nonsurvival RPLND, 5 with the protease activatable in vivo fluorescent molecular imaging agent, ProSense and 5 without image guidance (control). ProSense was administered 24 hours before surgery and detected 24 hours later using a photodynamic detector. In group 1, RPLND was first performed without molecular imaging followed by image-guided lymph node dissection for residual nodes. In group 2, the near infrared detector was used initially for lymph node excision followed by traditionally unassisted extraction of the residual lymph nodes. The lymph nodes were extracted, counted, and sent for histopathologic analysis. RESULTS: With the assistance of molecular imaging, no additional lymph nodes were identified after complete dissection, and all tissue identified by ProSense was confirmed by histopathologic analysis to be lymph nodes. Without molecular imaging, all lymph nodes were not identified, and in 2 instances, the tissue was incorrectly thought to be lymphatic tissue. CONCLUSIONS: Molecular image-guided RPLND is a promising technique to improve in vivo, live visualization and dissection of lymph nodes and has the potential for application in improving the diagnosis and treatment of other urologic malignancies.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21601249
      14. Call Number :
        PKI @ kd.modi @ 13
      15. Serial :
        10474
      1. Author :
        Leszczynska, K.; Namiot, D.; Byfield, F. J.; Cruz, K.; Zendzian-Piotrowska, M.; Fein, D. E.; Savage, P. B.; Diamond, S.; McCulloch, C. A.; Janmey, P. A.; Bucki, R.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        J Antimicrob Chemother
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen5, Xen 5, Pseudomonas aeruginosa
      12. Abstract :
        OBJECTIVES: We aim to develop antibacterial peptide mimics resistant to protease degradation, with broad-spectrum activity at sites of infection. METHODS: The bactericidal activities of LL-37, ceragenins CSA-13, CSA-90 and CSA-92 and the spermine-conjugated dexamethasone derivative D2S were evaluated using MIC and MBC measurements. Gingival fibroblast counting, interleukin-8 (IL-8) and lactate dehydrogenase (LDH) release from keratinocytes (HaCat) were used to determine effects on cell growth, pro-inflammatory response and toxicity. RESULTS: All tested cationic lipids showed stronger bactericidal activity than LL-37. Incubation of Staphylococcus aureus with half the MIC of LL-37 led to the appearance of bacteria resistant to its bactericidal effects, but identical incubations with CSA-13 or D2S did not produce resistant bacteria. Cathelicidin LL-37 significantly increased the total number of gingival fibroblasts, but ceragenins and D2S did not alter gingival fibroblast growth. Cationic lipids showed no toxicity to HaCat cells at concentrations resulting in bacterial killing. CONCLUSIONS: These data suggest that cationic lipids such as ceragenins warrant further testing as potential novel antibacterial agents.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/23134677
      14. Call Number :
        PKI @ kd.modi @ 6
      15. Serial :
        10551
      1. Author :
        Rahul A. Sheth, Marco Maricevich and Umar Mahmood
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Atherosclerosis
      6. Products :
      7. Volume :
        212
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        Cardiovascular Research
      11. Keywords :
        Molecular imaging; Abdominal aortic aneurysm; Optical imaging; Pre-clinical; Endovascular imaging; Matrix metalloproteinase; in vivo imaging; MMPSense
      12. Abstract :
        Objectives: We present a method to quantify the inflammatory processes that drive abdominal aortic aneurysm (AAA) development that may help predict the rate of growth and thus guide medical and surgical management. We use an in vivo optical molecular imaging approach to quantify protease activity within the walls of AAAs in a rodent model.

        Methods: AAAs were generated in mice by topical application of calcium chloride, followed by the administration of the MMP inhibitor doxycycline for 3 months. After this time period, an enzyme-activatable optical molecular imaging agent sensitive to MMP activity was administered, and MMP proteolytic activity was measured in vivo. Histology and in situ zymography were performed for validation. AAAs were also generated in rats, and MMP activity within the walls of the AAAs was also quantified endovascularly.

        Results: A dose-dependent response of AAA growth rate to doxycycline administration was demonstrated, with high doses of the drug resulting in nearly complete suppression of aneurysm formation. There was a direct relationship between the rate of aneurysmal growth and measured MMP activity, with a linear best-fit well approximating the relationship. We additionally performed endovascular imaging of AAAs in rats and demonstrated a similar suppression of intramural MMP activity following doxycycline administration.

        Conclusions: We present an in vivo evaluation of MMP activity within the walls of AAAs in rodents and show a direct, linear relationship between proteolytic activity and aneurysmal growth. We also illustrate that this functional imaging method can be performed endovascularly, demonstrating potential pre-clinical and clinical applications.
      13. URL :
        http://www.atherosclerosis-journal.com/article/S0021-9150(10)00390-4/abstract
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4550
      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 :
        Tekabe, Y.; Klose, A.; Nizami, S.; Luma, J.; Lee, F. Y.; Johnson, L.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        J Biophotonics
      6. Products :
      7. Volume :
        4
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IntegriSense, Animals; Antigens, CD31/metabolism; Capillaries/metabolism; Diagnostic Imaging/*methods; Femoral Artery/surgery; Fluorescent Dyes/*diagnostic use/metabolism; Hindlimb/*blood supply/metabolism/pathology; Integrin alphaV/metabolism; Integrin alphaVbeta3/antagonists & inhibitors/metabolism; Ischemia/*pathology; Ligation; Male; Mice; Mice, Inbred Strains; Microscopy, Fluorescence; *Neovascularization, Physiologic; Plant Lectins/metabolism; Sensitivity and Specificity
      12. Abstract :
        Optical agents targeting alpha(v)beta(3) are potential tools to image the angiogenic response to limb ischemia. The left (L) femoral artery was ligated in 17 mice and sham surgery performed on the contralateral right (R) hindlimb. Seven days later, IntegriSense (2 nmol) was injected into 11 mice and 6 were probe controls. Six hours later, mice underwent optical imaging. Ratios of photon flux in the L/R limbs were calculated. Tissue was stained for alpha(v) , CD31, and lectin. The signal was increased in the ischemic limbs compared to contralateral legs and ratio of photon flux in L/R limb averaged 2.37. Control probe showed no hindlimb signal. IntegriSense colocalized with CD31 by dual fluorescent staining. Ratios for L/R hindlimbs correlated with quantitative lectin staining (r = 0.88, p = 0.003). Optical imaging can identify and quantify angiogenic response to hindlimb ischemia.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22031282
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10380
      1. Author :
        Snoeks, T. J.; Khmelinskii, A.; Lelieveldt, B. P.; Kaijzel, E. L.; Lowik, C. W.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Bone
      6. Products :
      7. Volume :
        48
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IntegriSense, Animals; Bone Neoplasms/radionuclide imaging/*secondary; Diagnostic Imaging/*methods; Forecasting; Optics and Photonics/*trends; Positron-Emission Tomography/methods; Tomography, Emission-Computed, Single-Photon/methods; X-Ray Microtomography/methods; X-Rays
      12. Abstract :
        Optical Imaging has evolved into one of the standard molecular imaging modalities used in pre-clinical cancer research. Bone research however, strongly depends on other imaging modalities such as SPECT, PET, x-ray and muCT. Each imaging modality has its own specific strengths and weaknesses concerning spatial resolution, sensitivity and the possibility to quantify the signal. An increasing number of bone specific optical imaging models and probes have been developed over the past years. This review gives an overview of optical imaging modalities, models and probes that can be used to study skeletal complications of cancer in small laboratory animals.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20688203
      14. Call Number :
        PKI @ kd.modi @ 19
      15. Serial :
        10378
      1. Author :
        Snoeks, T. J.; Khmelinskii, A.; Lelieveldt, B. P.; Kaijzel, E. L.; Lowik, C. W.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Bone
      6. Products :
      7. Volume :
        48
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        OsteoSense, Animals; Bone Neoplasms/radionuclide imaging/*secondary; Diagnostic Imaging/*methods; Forecasting; Optics and Photonics/*trends; Positron-Emission Tomography/methods; Tomography, Emission-Computed, Single-Photon/methods; X-Ray Microtomography/methods; X-Rays
      12. Abstract :
        Optical Imaging has evolved into one of the standard molecular imaging modalities used in pre-clinical cancer research. Bone research however, strongly depends on other imaging modalities such as SPECT, PET, x-ray and muCT. Each imaging modality has its own specific strengths and weaknesses concerning spatial resolution, sensitivity and the possibility to quantify the signal. An increasing number of bone specific optical imaging models and probes have been developed over the past years. This review gives an overview of optical imaging modalities, models and probes that can be used to study skeletal complications of cancer in small laboratory animals.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20688203
      14. Call Number :
        PKI @ kd.modi @ 6
      15. Serial :
        10476
      1. Author :
        John Baeten; Jodi Haller; Helen Shih; Vasilis Ntziachristos
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Neoplasia
      6. Products :
      7. Volume :
        11
      8. Issue :
        3
      9. Page Numbers :
        N/A
      10. Research Area :
        Cancer
      11. Keywords :
        in vivo imaging; optical imaging; breast cancer; molecular imaging
      12. Abstract :
        Optical imaging of breast cancer has been considered for detecting functional and molecular characteristics of diseases in clinical and preclinical settings. Applied to laboratory research, photonic investigations offer a highly versatile tool for preclinical imaging and drug discovery. A particular advantage of the optical method is the availability of multiple spectral bands for performing imaging. Herein, we capitalize on this feature to demonstrate how it is possible to use different wavelengths to offer internal controls and significantly improve the observation accuracy in molecular imaging applications. In particular, we show the independent in vivo detection of cysteine proteases along with tumor permeability and interstitial volume measurements using a dual-wavelength approach. To generate results with a view toward clinically geared studies, a transgenic Her2/neu mouse model that spontaneously developed mammary tumors was used. In vivo findings were validated against conventional ex vivo tests such as histology and Western blot analyses. By correcting for biodistribution parameters, the dual-wavelength method increases the accuracy of molecular observations by separating true molecular target from probe biodistribution. As such, the method is highly appropriate for molecular imaging studies where often probe delivery and target presence are not independently assessed. On the basis of these findings, we propose the dual-wavelength/normalization approach as an essential method for drug discovery and preclinical imaging studies.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2647724/
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4494
      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
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