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      1. Author :
        Johnson, J. L.; Pillai, S.; Pernazza, D.; Sebti, S. M.; Lawrence, N. J.; Chellappan, S. P.
      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 :
        A549-luc-C8, A549-luc, IVIS, Bioware, Animals; Breast Neoplasms/genetics/metabolism/pathology; Carcinoma, Non-Small-Cell Lung/genetics/metabolism/pathology; Cell Line, Tumor; E2F Transcription Factors/*genetics/metabolism; Enzyme Assays/methods; Female; Gelatin/metabolism; *Gene Expression Regulation, Enzymologic; *Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms/genetics/metabolism/pathology; Matrix Metalloproteinases/biosynthesis/*genetics/metabolism; Mice; Mice, SCID; Neoplasm Metastasis; Phosphatidylethanolamine Binding Protein/*metabolism; Retinoblastoma Protein/genetics/*metabolism; Transcription, Genetic; Transfection
      12. Abstract :
        The retinoblastoma (Rb)-E2F transcriptional regulatory pathway plays a major role in cell-cycle regulation, but its role in invasion and metastasis is less well understood. We find that many genes involved in the invasion of cancer cells, such as matrix metalloproteinases (MMP), have potential E2F-binding sites in their promoters. E2F-binding sites were predicted on all 23 human MMP gene promoters, many of which harbored multiple E2F-binding sites. Studies presented here show that MMP genes such as MMP9, MMP14, and MMP15 which are overexpressed in non-small cell lung cancer, have multiple E2F-binding sites and are regulated by the Rb-E2F pathway. Chromatin immunoprecipitation assays showed the association of E2F1 with the MMP9, MMP14, and MMP15 promoters, and transient transfection experiments showed that these promoters are E2F responsive. Correspondingly, depletion of E2F family members by RNA interference techniques reduced the expression of these genes with a corresponding reduction in collagen degradation activity. Furthermore, activating Rb by inhibiting the interaction of Raf-1 with Rb by using the Rb-Raf-1 disruptor RRD-251 was sufficient to inhibit MMP transcription. This led to reduced invasion and migration of cancer cells in vitro and metastatic foci development in a tail vein lung metastasis model in mice. These results suggest that E2F transcription factors may play a role in promoting metastasis through regulation of MMP genes and that targeting the Rb-Raf-1 interaction is a promising approach for the treatment of metastatic disease.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22086850
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10525
      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 :
        Valdivia, Y. Alvarado M.; Wong, K.; Cheng He, T.; Xue, Z.; Wong, S. T.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        J Vasc Interv Radiol
      6. Products :
      7. Volume :
        22
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IntegriSense, Animals; Cell Line, Tumor; Fiber Optic Technology/*methods; Fluorescent Dyes/*administration & dosage/*diagnostic use; Humans; Injections, Intralesional; Lung Neoplasms/*pathology; Microscopy, Fluorescence/*methods; Molecular Imaging/*methods; Rabbits; Surgery, Computer-Assisted/*methods; Tomography, X-Ray Computed/methods
      12. Abstract :
        PURPOSE: To show the feasibility of computed tomography (CT) image-guided fiberoptic confocal fluorescence molecular imaging in a rabbit lung tumor model. MATERIALS AND METHODS: Eight lung tumor models were created by injection of a VX2 cell suspension. The fluorescent imaging agent IntegriSense 680 was given to the animals 3.5-4 hours before the procedure. CT images were obtained and transferred to the minimally invasive multimodality image-guided (MIMIG) system as a guidance map. A real-time electromagnetically tracked needle was inserted under the visual guidance of the MIMIG system. A second CT image was obtained to confirm the location of the needle tip. Next, fiberoptic fluorescence imaging was acquired along the needle track. Finally, tumor samples were obtained for histopathologic confirmation. RESULTS: All cases were performed during breath-hold. Tumor size was 12.5 mm +/- 1.6; the distance from the chest wall was 2.1 mm +/- 0.5. The needle tip reached the tumor in all cases with an accuracy of 3.3 mm +/- 1.6. Only one skin entry point was necessary, and no needle adjustments were required. No pneumothorax was observed. At least two-fold alpha(v)beta(3) integrin image contrast was detected in the tumor compared with normal lung tissue. Tumor samples were confirmed to have viable VX2 cells and contrast uptake. CONCLUSIONS: The MIMIG system enables effective in situ fluorescence molecular imaging in a needle biopsy lung procedure. In situ alpha(v)beta(3) integrin molecular imaging allows molecular characterization of lung tumors at multiple regions and can be used to guide biopsy procedures.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22019854
      14. Call Number :
        PKI @ kd.modi @ 14
      15. Serial :
        10383
      1. Author :
        Tafreshi, N. K.; Bui, M. M.; Bishop, K.; Lloyd, M. C.; Enkemann, S. A.; Lopez, A. S.; Abrahams, D.; Carter, B. W.; Vagner, J.; Grobmyer, S. R.; Gillies, R. J.; Morse, D. L.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Clin Cancer Res
      6. Products :
      7. Volume :
        18
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        VivoTag, IVIS, Vivotag, Animals; Antibodies, Monoclonal/*diagnostic use/immunology/pharmacokinetics; Antigens, Neoplasm/*metabolism; Blotting, Western; Breast/immunology/metabolism/pathology; Breast Neoplasms/*diagnosis/immunology/metabolism; Carbonic Anhydrases/*metabolism; Carcinoma, Ductal, Breast/*diagnosis/immunology/metabolism; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/immunology/metabolism; *Diagnostic Imaging; Female; Fluorescent Antibody Technique; Gene Expression Profiling; Humans; Luciferases/metabolism; Luminescent Measurements; Lymphatic Metastasis; Mice; Mice, Nude; Neoplasm Invasiveness; Oligonucleotide Array Sequence Analysis; RNA, Messenger/genetics; Real-Time Polymerase Chain Reaction; Tissue Array Analysis; Tissue Distribution; Tumor Cells, Cultured; Tumor Markers, Biological/genetics/metabolism
      12. Abstract :
        PURPOSE: To develop targeted molecular imaging probes for the noninvasive detection of breast cancer lymph node metastasis. EXPERIMENTAL DESIGN: Six cell surface or secreted markers were identified by expression profiling and from the literature as being highly expressed in breast cancer lymph node metastases. Two of these markers were cell surface carbonic anhydrase isozymes (CAIX and/or CAXII) and were validated for protein expression by immunohistochemistry of patient tissue samples on a breast cancer tissue microarray containing 47 normal breast tissue samples, 42 ductal carcinoma in situ, 43 invasive ductal carcinomas without metastasis, 46 invasive ductal carcinomas with metastasis, and 49 lymph node macrometastases of breast carcinoma. Targeted probes were developed by conjugation of CAIX- and CAXII-specific monoclonal antibodies to a near-infrared fluorescent dye. RESULTS: Together, these two markers were expressed in 100% of the lymph node metastases surveyed. Selectivity of the imaging probes were confirmed by intravenous injection into nude mice-bearing mammary fat pad tumors of marker-expressing cells and nonexpressing cells or by preinjection of unlabeled antibody. Imaging of lymph node metastases showed that peritumorally injected probes detected nodes harboring metastatic tumor cells. As few as 1,000 cells were detected, as determined by implanting, under ultrasound guidance, a range in number of CAIX- and CAXII-expressing cells into the axillary lymph nodes. CONCLUSION: These imaging probes have potential for noninvasive staging of breast cancer in the clinic and elimination of unneeded surgery, which is costly and associated with morbidities.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22016510
      14. Call Number :
        PKI @ kd.modi @ 3
      15. Serial :
        10568
      1. Author :
        Cheung, R.; Shen, F.; Phillips, J. H.; McGeachy, M. J.; Cua, D. J.; Heyworth, P. G.; Pierce, R. H.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        J Clin Invest
      6. Products :
      7. Volume :
        121
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, RediJect Inflammation Probe, chemiluminescence, XenoLight, Adaptor Proteins, Signal Transducing/metabolism; Animals; Cell Differentiation; Concanavalin A/toxicity; Dengue Hemorrhagic Fever/etiology; Disease Models, Animal; Disease Progression; Female; Humans; Immunity, Innate; Intracellular Signaling Peptides and Proteins/metabolism; Lectins, C-Type/deficiency/genetics/*immunology; Liver/metabolism/pathology; Mice; Mice, Inbred C57BL; Mice, Knockout; Models, Immunological; Myeloid Cells/*immunology/pathology; Nitric Oxide/biosynthesis; Nitric Oxide Synthase Type II/metabolism; Nitric Oxide Synthase Type III/metabolism; Phosphatidylinositol 3-Kinases/metabolism; Protein-Tyrosine Kinases/metabolism; Proto-Oncogene Proteins c-akt/metabolism; Receptors, Cell Surface/deficiency/genetics/*immunology; Receptors, Immunologic/metabolism; Shock/*etiology/*immunology/metabolism/pathology; Signal Transduction; Systemic Inflammatory Response; Syndrome/etiology/immunology/metabolism/pathology; Tumor Necrosis Factor-alpha/biosynthesis
      12. Abstract :
        Systemic inflammatory response syndrome (SIRS) is a potentially lethal condition, as it can progress to shock, multi-organ failure, and death. It can be triggered by infection, tissue damage, or hemorrhage. The role of tissue injury in the progression from SIRS to shock is incompletely understood. Here, we show that treatment of mice with concanavalin A (ConA) to induce liver injury triggered a G-CSF-dependent hepatic infiltration of CD11b+Gr-1+Ly6G+Ly6C+ immature myeloid cells that expressed the orphan receptor myeloid DAP12-associated lectin-1 (MDL-1; also known as CLEC5A). Activation of MDL-1 using dengue virus or an agonist MDL-1-specific antibody in the ConA-treated mice resulted in shock. The MDL-1+ cells were pathogenic, and in vivo depletion of MDL-1+ cells provided protection. Triggering MDL-1 on these cells induced production of NO and TNF-alpha, which were found to be elevated in the serum of treated mice and required for MDL-1-induced shock. Surprisingly, MDL-1-induced NO and TNF-alpha production required eNOS but not iNOS. Activation of DAP12, DAP10, Syk, PI3K, and Akt was critical for MDL-1-induced shock. In addition, Akt physically interacted with and activated eNOS. Therefore, triggering of MDL-1 on immature myeloid cells and production of NO and TNF-alpha may play a critical role in the pathogenesis of shock. Targeting the MDL-1/Syk/PI3K/Akt/eNOS pathway represents a potential new therapeutic strategy to prevent the progression of SIRS to shock.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22005300
      14. Call Number :
        PKI @ kd.modi @ 2
      15. Serial :
        10421
      1. Author :
        Fink, D.; Romanowski, K.; Valuckaite, V.; Babrowski, T.; Kim, M.; Matthews, J. B.; Liu, D.; Zaborina, O.; Alverdy, J. C.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        J Trauma
      6. Products :
      7. Volume :
        71
      8. Issue :
        N/A
      9. Page Numbers :
        1575-82
      10. Research Area :
        N/A
      11. Keywords :
        Xen41, Xen 41, Pseudomonas aeruginosa Xen41, IVIS
      12. Abstract :
        BACKGROUND: : Experimental models of intestinal ischemia-reperfusion (IIR) injury are invariably performed in mice harboring their normal commensal flora, even though multiple IIR events occur in humans during prolonged intensive care confinement when they are colonized by a highly pathogenic hospital flora. The aims of this study were to determine whether the presence of the human pathogen Pseudomonas aeruginosa in the distal intestine potentiates the lethality of mice exposed to IIR and to determine what role any in vivo virulence activation plays in the observed mortality. METHODS: : Seven- to 9-week-old C57/BL6 mice were exposed to 15 minutes of superior mesenteric artery occlusion (SMAO) followed by direct intestinal inoculation of 1.0 x 10 colony-forming unit of P. aeruginosa PAO1 into the ileum and observed for mortality. Reiterative studies were performed in separate groups of mice to evaluate both the migration/dissemination pattern and in vivo virulence activation of intestinally inoculated strains using live photon camera imaging of both a constitutive bioluminescent P. aeruginosa PAO1 derivative XEN41 and an inducible reporter derivative of PAO1, the PAO1/lecA:luxCDABE that conditionally expresses the quorum sensing-dependent epithelial disrupting virulence protein PA 1 Lectin (PA-IL). RESULTS: : Mice exposed to 15 minutes of SMAO and reperfusion with intestinal inoculation of P. aeruginosa had a significantly increased mortality rate (p < 0.001) of 100% compared with <10% for sham-operated mice intestinally inoculated with P. aeruginosa without SMAO and IIR alone (<50%). Migration/dissemination patterns of P. aeruginosa in mice subjected to IIR demonstrated proximal migration of distally injected strains and translocation to mesenteric lymph nodes, liver, spleen, lung, and kidney. A key role for in vivo virulence expression of the barrier disrupting adhesin PA-IL during IIR was established since its expression was enhanced during IR and mutant strains lacking PA-IL displayed attenuated mortality. CONCLUSIONS: : The presence of intestinal P. aeruginosa potentiates the lethal effect of IIR in mice in part due to in vivo virulence activation of its epithelial barrier disrupting protein PA-IL.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22002612
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10423
      1. Author :
        Las Heras, F.; DaCosta, R. S.; Pritzker, K. P.; Haroon, N.; Netchev, G.; Tsui, H. W.; Chiu, B.; Erwin, W. M.; Tsui, F. W.; Inman, R. D.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Arthritis Res Ther
      6. Products :
      7. Volume :
        13
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        OsteoSense, Animals; Axis/chemistry/*metabolism/*pathology; *Calcification, Physiologic/genetics; Inflammation/genetics/metabolism/prevention & control; Mice; Mice, Transgenic; Molecular Imaging/*methods; Spondylitis, Ankylosing/diagnosis/*genetics/*metabolism; Time Factors
      12. Abstract :
        INTRODUCTION: The diagnosis of ankylosing spondylitis is made from a combination of clinical features and the presence of radiographic evidence that may be detected only after many years of inflammatory back pain. It is not uncommon to have a diagnosis confirmed 5 to 10 years after the initial onset of symptoms. Development of a more-sensitive molecular imaging technology to detect structural changes in the joints would lead to earlier diagnosis and quantitative tracking of ankylosis progression. Progressive ankylosis (ank/ank) mice have a loss of function in the Ank gene, which codes for a regulator of PPi transport. In this study, we used these ank/ank mutant mice to assess a noninvasive, quantitative measure of joint ankylosis with near-infrared (NIR) molecular imaging in vivo. METHODS: Three age groups (8, 12, and 18 weeks) of ank/ank (15 mice) and wild-type littermates (12 +/+ mice) were assessed histologically and radiographically. Before imaging, OsteoSense 750 (bisphosphonate pamidronate) was injected i.v. Whole-body images were analyzed by using the multispectral Maestro imaging system. RESULTS: OsteoSense 750 signals in the paw joints were higher in ank/ank mice in all three age groups compared with controls. In the spine, significantly higher OsteoSense 750 signals were detected early, in 8-week-old ank/ank mice compared with controls, although minimal radiographic differences were noted at this time point. The molecular imaging changes in the ank/ank spine (8 weeks) were supported by histologic changes, including calcium apatite crystals at the edge of the vertebral bodies and new syndesmophyte formation. CONCLUSIONS: Changes in joint pathology of ank/ank mice, as evaluated by histologic and radiographic means, are qualitative, but only semiquantitative. In contrast, molecular imaging provides a quantitative assessment. Ankylosis in ank/ank mice developed simultaneously in distal and axial joints, contrary to the previous notion that it is a centripetal process. NIR imaging might be feasible for early disease diagnosis and for monitoring disease progression in ankylosing spondylitis.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21992149
      14. Call Number :
        PKI @ kd.modi @ 3
      15. Serial :
        10471
      1. Author :
        Korotcov, A. V.; Ye, Y.; Chen, Y.; Zhang, F.; Huang, S.; Lin, S.; Sridhar, R.; Achilefu, S.; Wang, P. C.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Mol Imaging Biol
      6. Products :
      7. Volume :
        14
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        PC-3M-luc-C6, PC-3M-luc, IVIS, Bioware, Prostate cancer, Bioluminescence, Animals; Cell Line, Tumor; Endocytosis; Fluorescent Dyes/chemistry/*diagnostic use; Glucosamine/chemistry/*diagnostic use; Humans; Kinetics; Male; Mice; Mice, Nude; Molecular Imaging/*methods; Neoplasms/*diagnosis/pathology; Optical Devices; Prostatic Neoplasms/diagnosis/pathology; Spectroscopy, Near-Infrared; Tissue Distribution; *Xenograft Model Antitumor Assays
      12. Abstract :
        PURPOSE: Near-infrared fluorescence (NIRF) imaging is an attractive technique for studying diseases at the molecular level in vivo. Glucose transporters are often used as targets for in vivo imaging of tumors. The efficiency of a tumor-seeking fluorescent probe can be enhanced by attaching one or more glucosamine (GlcN) moieties. This study was designed to evaluate the use of previously developed GlcN-linked NIRF probes for in vitro and in vivo optical imaging of cancer. PROCEDURES: Cellular uptake of the probes (1 muM) was investigated in monolayer cultures of luciferase-expressing PC3 (PC3-luc) cells. The prostate tumors were established as subcutaneous xenografts using PC3-luc cells in nude mice. The biodistributions and tumor-targeting specificities of cypate (cyp), cypate-D: -(+)-glucosamine (cyp-GlcN), and D: -(+)-gluosamine-cypate-D: -(+)-gluosamine (cyp-2GlcN) were studied. The tumor, muscle, and major organs were collected for ex vivo optical imaging. RESULTS: The tumor cell uptake of the probe containing two glucosamine residues, cyp-2GlcN, was significantly higher than the uptake of both the probe with one glucosamine residue, cyp-GlcN, and the probe without glucosamine, cyp only. Similarly, in in vivo experiments, cyp-2GlcN demonstrated higher maximum fluorescence intensity and longer residence lifetime in tumors than cyp-GlcN or cyp. The ex vivo biodistribution analysis revealed that tumor uptake of cyp-2GlcN and cyp-GlcN was four- and twofold higher than that of cyp at 24 h post-injection, respectively. CONCLUSION: Both cyp-GlcN and cyp-2GlcN NIRF probes exhibited good tumor-targeting properties in prostate cancer cell cultures and live mice. The cyp-2GlcN probe showed the highest uptake with good retention characteristics in vivo. The uptake of cyp-2GlcN and cyp-GlcN is likely mediated by glucosamine-recognizing transporters. The uptake mechanism is being explored further for developing cypate-glucosamine-based probes for in vivo imaging.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21971932
      14. Call Number :
        PKI @ kd.modi @ 3
      15. Serial :
        10536
      1. Author :
        Nakayama, H.; Kawase, T.; Okuda, K.; Wolff, L. F.; Yoshie, H.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Acta Radiol
      6. Products :
      7. Volume :
        52
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        OsteoSense,, Animals; Bone Neoplasms/*pathology/physiopathology; Calcification, Physiologic/*physiology; Diphosphonates/diagnostic use; Feasibility Studies; Inositol/analogs & derivatives/diagnostic use; Mice; Mice, Hairless; Osteosarcoma/*pathology/physiopathology; Radiopharmaceuticals/diagnostic use; Spectroscopy, Near-Infrared/*methods; Technetium Tc 99m Medronate/analogs & derivatives/diagnostic use; Transplantation, Heterologous
      12. Abstract :
        BACKGROUND: In a previous study using a rodent osteosarcoma-grafted rat model, in which cell-dependent mineralization was previously demonstrated to proportionally increase with growth, we performed a quantitative analysis of mineral deposit formation using (99m)Tc-HMDP and found some weaknesses, such as longer acquisition time and narrower dynamic ranges (i.e. images easily saturated). The recently developed near-infrared (NIR) optical imaging technique is expected to non-invasively evaluate changes in living small animals in a quantitative manner. PURPOSE: To test the feasibility of NIR imaging with a dual-channel system as a better alternative for bone scintigraphy by quantitatively evaluating mineralization along with the growth of osteosarcoma lesions in a mouse-xenograft model. MATERIAL AND METHODS: The gross volume and mineralization of osteosarcoma lesions were evaluated in living mice simultaneously with dual-channels by NIR dye-labeled probes, 2-deoxyglucose (DG) and pamidronate (OS), respectively. To verify these quantitative data, retrieved osteosarcoma lesions were then subjected to ex-vivo imaging, weighing under wet conditions, microfocus-computed tomography (muCT) analysis, and histopathological examination. RESULTS: Because of less scattering and no anatomical overlapping, as generally shown, specific fluorescence signals targeted to the osteosarcoma lesions could be determined clearly by ex-vivo imaging. These data were well positively correlated with the in-vivo imaging data (r > 0.8, P < 0.02). Other good to excellent correlations (r > 0.8, P < 0.02) were observed between DG accumulation and tumor gross volume and between OS accumulation and mineralization volume. CONCLUSION: This in-vivo NIR imaging technique using DG and OS is sensitive to the level to simultaneously detect and quantitatively evaluate the growth and mineralization occuring in this type of osteosarcoma lesions of living mice without either invasion or sacrifice. By possible mutual complementation, this dual imaging system might be useful for accurate diagnosis even in the presence of overlapping tissues.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21969703
      14. Call Number :
        PKI @ kd.modi @ 7
      15. Serial :
        10472
      1. Author :
        Keereweer, S.; Mol, I. M.; Kerrebijn, J. D.; Van Driel, P. B.; Xie, B.; Baatenburg de Jong, R. J.; Vahrmeijer, A. L.; Lowik, C. W.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        J Surg Oncol
      6. Products :
      7. Volume :
        105
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IntegriSense, Animals; Carcinoma, Squamous Cell/*pathology/surgery; Fluorescent Dyes/*diagnostic use; Humans; Integrin alphaVbeta3/*metabolism; Mice; Mice, Inbred BALB C; Mouth Neoplasms/*pathology/surgery; Spectroscopy, Near-Infrared; *Surgery, Computer-Assisted
      12. Abstract :
        BACKGROUND AND OBJECTIVES: Near-infrared (NIR) fluorescence optical imaging is a promising technique to assess the tumor margins during cancer surgery. This technique requires targeting by specific fluorescence agents to differentiate tumor from normal surrounding tissue. We assessed the feasibility of cancer detection using NIR fluorescence agents that target either alphavbeta3 integrins or the enhanced permeability and retention (EPR) effect in an orthotopic mouse model of oral cancer. METHODS: Binding of the integrin-targeted agent to tumor cells was assessed in vitro. Oral cancer was induced in 6 BALB/c nu/nu mice by submucosal inoculation of human OSC19-luc cells into the tongue. Tumor growth was followed with bioluminescence imaging. A combination of agents targeting integrins or EPR effect was injected followed by fluorescence imaging in vivo and ex vivo after resection of the tongues. RESULTS: Oral cancer was clearly demarcated in vitro; in vivo; and on histological analysis with sufficient tumor-to-background ratios of the contrast agents. CONCLUSION: This study demonstrates the feasibility of optical imaging of oral squamous cell carcinoma based on targeting of alphavbeta3 integrins and the EPR effect. Once these NIR fluorescence agents become available for clinical testing, optical image-guided surgery could reduce residual disease after oral cancer surgery.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21952950
      14. Call Number :
        PKI @ kd.modi @ 28
      15. Serial :
        10368