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      1. Author :
        Proulx, S. T.; Luciani, P.; Derzsi, S.; Rinderknecht, M.; Mumprecht, V.; Leroux, J. C.; Detmar, M.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Cancer Res
      6. Products :
      7. Volume :
        70
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals, B16-F10-luc2, B16F10-luc2; Coloring Agents/administration & dosage/*diagnostic use; Indocyanine Green/administration & dosage/*diagnostic use; Injections, Intradermal; Liposomes/administration & dosage; Lymphatic Metastasis; Lymphatic Vessels/metabolism/*pathology; Melanoma, Experimental/blood supply/metabolism/*pathology; Mice; Mice, Inbred C57BL; Vascular Endothelial Growth Factor C/biosynthesis
      12. Abstract :
        Lymphatic vessels play a major role in cancer progression and in postsurgical lymphedema, and several new therapeutic approaches targeting lymphatics are currently being developed. Thus, there is a critical need for quantitative imaging methods to measure lymphatic flow. Indocyanine green (ICG) has been used for optical imaging of the lymphatic system, but it is unstable in solution and may rapidly enter venous capillaries after local injection. We developed a novel liposomal formulation of ICG (LP-ICG), resulting in vastly improved stability in solution and an increased fluorescence signal with a shift toward longer wavelength absorption and emission. When injected intradermally to mice, LP-ICG was specifically taken up by lymphatic vessels and allowed improved visualization of deep lymph nodes. In a genetic mouse model of lymphatic dysfunction, injection of LP-ICG showed no enhancement of draining lymph nodes and slower clearance from the injection site. In mice bearing B16 luciferase-expressing melanomas expressing vascular endothelial growth factor-C (VEGF-C), sequential near-IR imaging of intradermally injected LP-ICG enabled quantification of lymphatic flow. Increased flow through draining lymph nodes was observed in mice bearing VEGF-C-expressing tumors without metastases, whereas a decreased flow pattern was seen in mice with a higher lymph node tumor burden. This new method will likely facilitate quantitative studies of lymphatic function in preclinical investigations and may also have potential for imaging of lymphedema or improved sentinel lymph detection in cancer.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20823159
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10350
      1. Author :
        Mieog, J. S.; Hutteman, M.; van der Vorst, J. R.; Kuppen, P. J.; Que, I.; Dijkstra, J.; Kaijzel, E. L.; Prins, F.; Lowik, C. W.; Smit, V. T.; van de Velde, C. J.; Vahrmeijer, A. L.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Breast Cancer Res Treat
      6. Products :
      7. Volume :
        128
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        ProSense, IVIS, Animals; Breast Neoplasms/pathology/*surgery; Cell Line, Tumor; Disease Models, Animal; Female; *Microscopy, Fluorescence; Rats; *Surgery, Computer-Assisted; Transplantation, Isogeneic; Xenograft Model Antitumor Assays
      12. Abstract :
        Tumor involvement of resection margins is found in a large proportion of patients who undergo breast-conserving surgery. Near-infrared (NIR) fluorescence imaging is an experimental technique to visualize cancer cells during surgery. To determine the accuracy of real-time NIR fluorescence imaging in obtaining tumor-free resection margins, a protease-activatable NIR fluorescence probe and an intraoperative camera system were used in the EMR86 orthotopic syngeneic breast cancer rat model. Influence of concentration, timing and number of tumor cells were tested in the MCR86 rat breast cancer cell line. These variables were significantly associated with NIR fluorescence probe activation. Dosing and tumor size were also significantly associated with fluorescence intensity in the EMR86 rat model, whereas time of imaging was not. Real-time NIR fluorescence guidance of tumor resection resulted in a complete resection of 17 out of 17 tumors with minimal excision of normal healthy tissue (mean minimum and a mean maximum tumor-free margin of 0.2 +/- 0.2 mm and 1.3 +/- 0.6 mm, respectively). Moreover, the technique enabled identification of remnant tumor tissue in the surgical cavity. Histological analysis revealed that the NIR fluorescence signal was highest at the invasive tumor border and in the stromal compartment of the tumor. In conclusion, NIR fluorescence detection of breast tumor margins was successful in a rat model. This study suggests that clinical introduction of intraoperative NIR fluorescence imaging has the potential to increase the number of complete tumor resections in breast cancer patients undergoing breast-conserving surgery.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20821347
      14. Call Number :
        PKI @ kd.modi @ 4
      15. Serial :
        10429
      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 :
        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 :
        Chantry, A. D.; Heath, D.; Mulivor, A. W.; Pearsall, S.; Baud'huin, M.; Coulton, L.; Evans, H.; Abdul, N.; Werner, E. D.; Bouxsein, M. L.; Key, M. L.; Seehra, J.; Arnett, T. R.; Vanderkerken, K.; Croucher, P.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        J Bone Miner Res
      6. Products :
      7. Volume :
        25
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        MDA-MB-231-D3H2Ln, IVIS, Bioluminescence, Activins/*metabolism; Animals; Bone Neoplasms/*complications/pathology/physiopathology/secondary; Bone Resorption/*etiology/pathology/physiopathology/*prevention & control; Calcification, Physiologic/drug effects; Cell Line, Tumor; HEK293 Cells; Humans; Mice; Multiple Myeloma/complications/pathology/physiopathology; Neoplasm Transplantation; Organ Size/drug effects; Osteoblasts/drug effects/pathology; *Osteogenesis/drug effects; Osteolysis/blood/complications/physiopathology/prevention & control; Paraproteins/metabolism; Recombinant Fusion Proteins/pharmacology; *Signal Transduction/drug effects; Survival Analysis; Tumor Burden/drug effects
      12. Abstract :
        Cancers that grow in bone, such as myeloma and breast cancer metastases, cause devastating osteolytic bone destruction. These cancers hijack bone remodeling by stimulating osteoclastic bone resorption and suppressing bone formation. Currently, treatment is targeted primarily at blocking bone resorption, but this approach has achieved only limited success. Stimulating osteoblastic bone formation to promote repair is a novel alternative approach. We show that a soluble activin receptor type IIA fusion protein (ActRIIA.muFc) stimulates osteoblastogenesis (p < .01), promotes bone formation (p < .01) and increases bone mass in vivo (p < .001). We show that the development of osteolytic bone lesions in mice bearing murine myeloma cells is caused by both increased resorption (p < .05) and suppression of bone formation (p < .01). ActRIIA.muFc treatment stimulates osteoblastogenesis (p < .01), prevents myeloma-induced suppression of bone formation (p < .05), blocks the development of osteolytic bone lesions (p < .05), and increases survival (p < .05). We also show, in a murine model of breast cancer bone metastasis, that ActRIIA.muFc again prevents bone destruction (p < .001) and inhibits bone metastases (p < .05). These findings show that stimulating osteoblastic bone formation with ActRIIA.muFc blocks the formation of osteolytic bone lesions and bone metastases in models of myeloma and breast cancer and paves the way for new approaches to treating this debilitating aspect of cancer.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20533325
      14. Call Number :
        PKI @ kd.modi @ 4
      15. Serial :
        10413
      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 :
        Krespi, Y. P.; Kizhner, V.; Nistico, L.; Hall-Stoodley, L.; Stoodley, P.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Am J Otolaryngol
      6. Products :
      7. Volume :
        32
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen31, Xen 31, MRSA, S. aureus, IVIS, Bioluminescence, Biofilms/drug effects/*radiation effects; Ciprofloxacin/*pharmacology; Culture Media; High-Energy Shock Waves; Humans; *Laser Therapy, Low-Level; Methicillin-Resistant Staphylococcus aureus/*growth &; development/physiology/*radiation effects; Microbial Sensitivity Tests; Reference Values; Sensitivity and Specificity; Spectroscopy, Near-Infrared; Staphylococcal Infections/drug therapy
      12. Abstract :
        OBJECTIVE: The aim of the study was to study the efficacy of 2 different lasers in vitro, in disrupting biofilm and killing planktonic pathogenic bacteria. MATERIALS AND METHODS: Biofilms of a stable bioluminescent of Staphylococcus aureus Xen 31 were grown in a 96-well microtiter plate for 3 days. The study included 7 arms: (a) control; (b) ciprofloxacin (3 mg/L, the established minimum inhibitory concentration [MIC]) alone; (c) shock wave (SW) laser alone; (d) near-infrared (NIR) laser alone; (e) SW laser and ciprofloxacin; (f) SW and NIR lasers; (g) SW, NIR lasers, and ciprofloxacin. The results were evaluated with an in vivo imaging system (IVIS) biophotonic system (for live bacteria) and optical density (OD) for total bacteria. RESULTS: Without antibiotics, there was a 43% reduction in OD (P < .05) caused by the combination of SW and NIR suggesting that biofilm had been disrupted. There was an 88% reduction (P < .05) in live biofilm. Ciprofloxacin alone resulted in a decrease of 28% of total live cells (biofilm remaining attached) and 58% of biofilm cells (both P > .05). Ciprofloxacin in combination with SW and SW + NIR lasers caused a decrease of more than 60% in total live biomass and more than 80% of biofilm cells, which was significantly greater than ciprofloxacin alone (P < .05). CONCLUSIONS: We have demonstrated an effective nonpharmacologic treatment method for methicillin-resistant Staphylococcus aureus (MRSA) biofilm disruption and killing using 2 different lasers. The preferred treatment sequence is a SW laser disruption of biofilm followed by NIR laser illumination. Treatment optimization of biofilm is possible with the addition of ciprofloxacin in concentrations consistent with planktonic MIC.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20434806
      14. Call Number :
        PKI @ kd.modi @ 2
      15. Serial :
        10554
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