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      1. Author :
        Korotcov, A. V.; Ye, Y.; Chen, Y.; Zhang, F.; Huang, S.; Lin, S.; Sridhar, R.; Achilefu, S.; Wang, P. C.
      2. Title :
        Glucosamine-linked near-infrared fluorescent probes for imaging of solid tumor xenografts
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Mol Imaging Biol
      6. Products :

        Bioware cell linesIVIS Imaging Systems

      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 :
        Penna, F. J.; Chow, J. S.; Minnillo, B. J.; Passerotti, C. C.; Barnewolt, C. E.; Treves, S. T.; Fahey, F. H.; Dunning, P. S.; Freilich, D. A.; Retik, A. B.; Nguyen, H. T.
      2. Title :
        Identifying ureteropelvic junction obstruction by fluorescence imaging: a comparative study of imaging modalities to assess renal function and degree of obstruction in a mouse model
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        J Urol
      6. Products :

        OsteoSense

      7. Volume :
        185
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        OsteoSense, Animals; Diagnostic Imaging; Disease Models, Animal; Fluorescence; *Kidney Pelvis; Mice; Ureteral Obstruction/*diagnosis
      12. Abstract :
        PURPOSE: Radiological imaging is the mainstay of diagnosing ureteropelvic junction obstruction. Current established radiological modalities can potentially differentiate the varying degrees of obstruction but they are limited in functionality, applicability and/or comprehensiveness. Of particular concern is that some tests require radiation, which has long-term consequences, especially in children. MATERIALS AND METHODS: We investigated the novel use of Genhance 680 dynamic fluorescence imaging to assess ureteropelvic junction obstruction in 20 mice that underwent partial or complete unilateral ureteral obstruction. Ultrasound, mercaptoacetyltriglycine renography, magnetic resonance imaging and fluorescence imaging were performed. RESULTS: Our model of partial and complete obstruction could be distinguished by ultrasound, mercaptoacetyltriglycine renography and magnetic resonance imaging, and was confirmed by histological analysis. Using fluorescence imaging distinct vascular and urinary parameters were identified in the partial and complete obstruction groups compared to controls. CONCLUSIONS: Fluorescence imaging is a feasible alternative radiological imaging modality to diagnose ureteropelvic junction obstruction. It provides continuous, detailed imaging without the risk of radiation exposure.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21511294
      14. Call Number :
        PKI @ kd.modi @ 14
      15. Serial :
        10473
      1. Author :
        Stelter, L.; Tseng, J. C.; Torosjan, A.; Levin, B.; Longo, V. A.; Pillarsetty, N.; Zanzonico, P.; Meruelo, D.; Larson, S. M.
      2. Title :
        Tumor-Specific Targeting With Modified Sindbis Viral Vectors: Evaluation with Optical Imaging and Positron Emission Tomography In Vivo
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Mol Imaging Biol
      6. Products :

        AngioSenseFMT Imaging SystemsIVIS Imaging Systems

      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        AngioSense, FMT, IVIS, Biolumninescence
      12. Abstract :
        PURPOSE: Sindbis virus (SINV) infect tumor cells specifically and systemically throughout the body. Sindbis vectors are capable of expressing high levels of transduced suicide genes and thus efficiently produce enzymes for prodrug conversion in infected tumor cells. The ability to monitor suicide gene expression levels and viral load in patients, after administration of the vectors, would significantly enhance this tumor-specific therapeutic option. PROCEDURES: The tumor specificity of SINV is mediated by the 67-kDa laminin receptor (LR). We probed different cancer cell lines for their LR expression and, to determine the specific role of LR-expression in the infection cycle, used different molecular imaging strategies, such as bioluminescence, fluorescence molecular tomography, and positron emission tomography, to evaluate SINV-mediated infection in vitro and in vivo. RESULTS: All cancer cell lines showed a marked expression of LR. The infection rates of the SINV particles, however, differed significantly among the cell lines. CONCLUSION: We used novel molecular imaging techniques to visualize vector delivery to different neoplatic cells. SINV infection rates proofed to be not solely dependent on cellular LR expression. Further studies need to evaluate the herein discussed ways of cellular infection and viral replication.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22847302
      14. Call Number :
        PKI @ kd.modi @ 3
      15. Serial :
        10440
      1. Author :
        Sawada, R.; Sun, S. M.; Wu, X.; Hong, F.; Ragupathi, G.; Livingston, P. O.; Scholz, W. W.
      2. Title :
        Human monoclonal antibodies to sialyl-Lewisa (CA19.9) with potent CDC, ADCC, and antitumor activity
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Clin Cancer Res
      6. Products :

        Bioware cell linesIVIS Imaging Systems

      7. Volume :
        17
      8. Issue :
        N/A
      9. Page Numbers :
        1024-32
      10. Research Area :
        N/A
      11. Keywords :
        Colo205-luc2, colorectal cancer, Bioware, IVIS
      12. Abstract :
        PURPOSE: The carbohydrate antigen sialyl-Lewis(a) (sLe(a)), also known as CA19.9, is widely expressed on epithelial tumors of the gastrointestinal tract and breast and on small-cell lung cancers. Since overexpression of sLe(a) appears to be a key event in invasion and metastasis of many tumors and results in susceptibility to antibody-mediated lysis, sLe(a) is an attractive molecular target for tumor therapy. EXPERIMENTAL DESIGN: We generated and characterized fully human monoclonal antibodies (mAb) from blood lymphocytes from individuals immunized with a sLe(a)-KLH vaccine. RESULTS: Several mAbs were selected based on ELISA and FACS including two mAbs with high affinity for sLe(a) (5B1 and 7E3, binding affinities 0.14 and 0.04 nmol/L, respectively) and further characterized. Both antibodies were specific for Neu5Acalpha2-3Galbeta1-3(Fucalpha1-4)GlcNAcbeta as determined by glycan array analysis. Complement-dependent cytotoxicity against DMS-79 cells was higher (EC(50) 0.1 mug/mL vs. 1.7 mug/mL) for r7E3 (IgM) than for r5B1 (IgG1). In addition, r5B1 antibodies showed high level of antibody-dependent cell-mediated cytotoxicity activity on DMS-79 cells with human NK cells or peripheral blood mononuclear cells. To evaluate in vivo efficacy, the antibodies were tested in a xenograft model with Colo205 tumor cells engrafted into SCID (severe combined immunodeficient mice) mice. Treatment during the first 21 days with four doses of r5B1 (100 mug per dose) doubled the median survival time to 207 days, and three of five animals survived with six doses. CONCLUSION: On the basis of the potential of sLe(a) as a target for immune attack and their affinity, specificity, and effector functions, 5B1and 7E3 may have clinical utility.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21343375
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10502
      1. Author :
        Ran, C.; Zhang, Z.; Hooker, J.; Moore, A.
      2. Title :
        In vivo photoactivation without “light”: use of Cherenkov radiation to overcome the penetration limit of light
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Mol Imaging Biol
      6. Products :

        Bioware cell linesIVIS Imaging Systems

      7. Volume :
        14
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        MDA-MB-231-D3H1, MDA-MB-231-luc-D3H1, IVIS, Bioware, Breast Cancer. Animals; Cell Line, Tumor; Chromatography, Liquid; Diagnostic Imaging/*methods; *Elementary Particles; Firefly Luciferin/chemistry/metabolism; Fluorodeoxyglucose F18/diagnostic use; Humans; *Light; Luminescent Measurements; Mass Spectrometry; Mice; Mice, Nude; Solutions
      12. Abstract :
        PURPOSE: The poor tissue penetration of visible light has been a major barrier for optical imaging, photoactivatable conversions, and photodynamic therapy for in vivo targets with depths beyond 10 mm. In this report, as a proof-of-concept, we demonstrated that a positron emission tomography (PET) radiotracer, 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)FDG), could be used as an alternative light source for photoactivation. PROCEDURES: We utilized (18)FDG, which is a metabolic activity-based PET probe, as a source of light to photoactivate caged luciferin in a breast cancer animal model expressing luciferase. RESULTS: Bioluminescence produced from luciferin allowed for the real-time monitoring of Cherenkov radiation-promoted uncaging of the substrate. CONCLUSION: The proposed method may provide a very important option for in vivo photoactivation, in particular for activation of photosensitizers for photodynamic therapy and eventually for combining radioisotope therapy and photodynamic therapy.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21538154
      14. Call Number :
        PKI @ kd.modi @ 3
      15. Serial :
        10517
      1. Author :
        Kim, J. K.; Won, Y. W.; Lim, K. S.; Kim, Y. H.
      2. Title :
        Low-molecular-weight methylcellulose-based thermo-reversible gel/pluronic micelle combination system for local and sustained docetaxel delivery
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Pharm Res
      6. Products :

        Bioware cell linesIVIS Imaging Systems

      7. Volume :
        29
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, B16-F10-luc-G5, B16F10-luc-G5, B16-F10-luc, B16F10-luc, Animals; Antineoplastic Agents/*administration & dosage/pharmacokinetics/therapeutic use; Delayed-Action Preparations/*chemistry; Male; Methylcellulose/*chemistry; Mice; Mice, Inbred C57BL; *Micelles; Neoplasms/drug therapy; Poloxamer/*chemistry; Taxoids/*administration & dosage/pharmacokinetics/therapeutic use
      12. Abstract :
        PURPOSE: To develop low-molecular-weight methylcellulose (LMw MC)-based gel/Pluronic F127 micelle combination system for local and sustained delivery of docetaxel (DTX). METHODS: LMw MC and Pluronic F127 were used to formulate an injectable thermo-reversible gel/micelle combination system containing DTX. The DTX-loaded combination system was characterized and its therapeutic efficacy evaluated in a subcutaneous tumor model. RESULTS: Mixtures of LMw MC, AS, and Pluronic F127 formed gel at ~15-40 degrees C depending on AS concentration. The combination system released DTX for >30 days with a biphasic and sustained release pattern, and DTX stability was maintained during release. The combination system significantly enhanced anti-cancer effects of DTX and prolonged survival of the model mouse in comparison with free DTX. CONCLUSIONS: The LMw MC gel/Pluronic F127 micelle combination system constitutes a promising tool for reducing tumor size and eradicating remaining tumor cells before and after surgery.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21904934
      14. Call Number :
        PKI @ kd.modi @ 16
      15. Serial :
        10531
      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 :
        Noninvasive detection of breast cancer lymph node metastasis using carbonic anhydrases IX and XII targeted imaging probes
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Clin Cancer Res
      6. Products :

        VivoTagIVIS Imaging Systems

      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 :
        Carlisle, R.; Seymour, L. W.; Coussios, C. C.
      2. Title :
        Targeting of Liposomes via PSGL1 for Enhanced Tumor Accumulation
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Pharm Res
      6. Products :

        Bioware cell linesIVIS Imaging Systems

      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, B16-F10-luc-G5, B16F10-luc-G5, B16-F10-luc, B16F10-luc
      12. Abstract :
        PURPOSE: To improve the delivery of liposomes to tumors using P-selectin glycoprotein ligand 1 (PSGL1) mediated binding to selectin molecules, which are upregulated on tumorassociated endothelium. METHODS: PSGL1 was orientated and presented on the surface of liposomes to achieve optimal selectin binding using a novel streptavidin-protein G linker molecule. Loading of PSGL1 liposomes with luciferin allowed their binding to e-selectin and activated HUVEC to be quantified in vitro and their stability, pharmacokinetics and tumor accumulation to be tested in vivo using murine models. RESULTS: PSGL1 liposomes showed 5-fold (p < 0.05) greater selectin binding than identically formulated control liposomes modified with ligand that did not contain the selectin binding domain. When added to HUVEC, PSGL1 liposomes showed >7-fold (p < 0.001) greater attachment than control liposomes. In in vivo studies PSGL1 liposomes showed similar stability and circulation to control liposomes but demonstrated a >3-fold enhancement in the level of delivery to tumors (p < 0.05). CONCLUSIONS: The technologies and strategies described here may contribute to clinical improvements in the selectivity and efficacy of liposomal drug delivery agents.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22992830
      14. Call Number :
        PKI @ kd.modi @ 19
      15. Serial :
        10529
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