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638 results on '"Josephson, Lee"'

101. Multispectral visualization of surgical safety-margins using fluorescent marker seeds

Author

Chin, Patrick TK, Beekman, Chantal AC, Buckle, Tessa, Josephson, Lee, and van Leeuwen, Fijs WB

Subjects
technology, industry, and agriculture, Original Article, equipment and supplies
Abstract

Optical guidance provided by luminescent marker seeds may be suitable for intraoperative determination of appropriate resection margins. In phantom studies we compared the tissue penetration of several organic dyes and inorganic particles (quantum dots; QDs) after incorporation in experimental marker seeds. The tissue penetration of (near infra-) red organic dyes was much better than the penetration of dyes and QDs with an emission in the visible range. By combining 3 dyes in a single marker seed we were able to distinguish four depth ranges. The difference in tissue penetration between the dyes and QDS enabled depth estimation via a 'traffic light' approach.

Published
2012

102. Hybrid peptide dendrimers for imaging of CXCR4 expression

Author

Kuil, Joeri, Buckle, Tessa, Oldenburg, Joppe, Yuan, Hushan, Josephson, Lee, and van Leeuwen, Fijs W.B.

Subjects
Diagnostic Imaging, Models, Molecular, Dendrimers, Receptors, CXCR4, Microscopy, Confocal, Molecular Structure, Cell Survival, Gene Expression Profiling, Article, Gene Expression Regulation, Cell Line, Tumor, Humans, Peptides, Dimerization, Fluorescent Dyes
Abstract

The chemokine receptor 4 (CXCR4), which is overexpressed in many types of cancer, is an emerging target in the field of molecular imaging and therapeutics. The CXCR4 binding of several peptides, including the cyclic Ac-TZ14011, has already been validated. In this study mono-, di- and tetrameric Ac-TZ14011-containing dendrimers were prepared and functionalized with a multimodal (hybrid) label, consisting of a Cy5.5-like fluorophore and a DTPA chelate. Confocal microscopy revealed that all three dendrimers were membrane bound at 4 °C, consistent with CXCR4 binding in vitro. The unlabeled dimer and tetramer had a somewhat lower affinity for CXCR4 than the unlabeled monomer. However, when labeled with the multimodal label the CXCR4 affinity of the dimer and tetramer was considerably higher compared to that of the labeled monomer. On top of that, biodistribution studies revealed that the additional peptides in the dimer and tetramer reduced nonspecific muscle uptake. Thus, multimerization of the cyclic Ac-TZ14011 peptide reduces the negative influence of the multimodal label on the receptor affinity and the biodistribution.

Published
2011

103. Molecular MRI of Acute Necrosis with a Novel DNA-Binding Gadolinium Chelate: Kinetics of Cell Death and Clearance in Infarcted Myocardium: Huang et al: Molecular MRI of Acute Necrosis

Author

Huang, Shuning, Chen, Howard H., Yuan, Hushan, Dai, Guangping, Schuhle, Daniel T., Mekkaoui, Choukri, Ngoy, Soeun, Liao, Ronglih, Caravan, Peter, Josephson, Lee, and Sosnovik, David E.

Subjects
Gadolinium DTPA, Analysis of Variance, Binding Sites, Cell Death, Myocardial Infarction, DNA, Magnetic Resonance Imaging, Article, Mice, Inbred C57BL, Disease Models, Animal, Mice, Necrosis, Microscopy, Fluorescence, Acute Disease, Animals, Myocytes, Cardiac, Molecular Biology
Abstract

Current techniques to image cell death in the myocardium are largely nonspecific. We report the use of a novel DNA-binding gadolinium chelate (Gd-TO) to specifically detect the exposed DNA in acutely necrotic (ruptured) cells in vivo.In vivo MRI was performed in 20 mice with myocardial infarction (MI). The mice were injected with Gd-TO or Gd-DTPA at varying time points after MI. MRI was performed 2 hours after probe injection, to avoid nonspecific signal from the late gadolinium enhancement effect. Cell rupture (Gd-TO uptake) was present within 2 hours of infarction but peaked 9 to 18 hours after the onset of injury. A significant increase in the longitudinal relaxation rate (R(1)) in the infarct was seen in mice injected with Gd-TO within 48 hours of MI, but not in those injected more than 72 hours after MI (R(1)=1.24±0.08 and 0.92±0.03 s(-1), respectively, P0.001). Gd-DTPA, unlike Gd-TO, washed completely out of acute infarcts within 2 hours of injection (P0.001). The binding of Gd-TO to exposed DNA in acute infarcts was confirmed with fluorescence microscopy.Gd-TO specifically binds to acutely necrotic cells and can be used to image the mechanism and chronicity of cell death in injured myocardium. Cell rupture in acute MI begins early but peaks many hours after the onset of injury. The ruptured cells are efficiently cleared by the immune system and are no longer present in the myocardium 72 hours after injury.

Published
2011

104. Synthesis and in vitro evaluation of a bimodal CXCR4 antagonistic peptide

Author

Kuil, Joeri, Yuan, Hushan, Buckle, Tessa, Oishi, Shinya, Fujii, Nobutaka, Josephson, Lee, and van Leeuwen, Fijs W.B.

Subjects
Mice, Receptors, CXCR4, Microscopy, Confocal, Molecular Conformation, Animals, Humans, Pentetic Acid, Flow Cytometry, Peptides, Article, Chelating Agents, Fluorescent Dyes
Abstract

The antagonistic Ac-TZ14011 peptide, which binds to the chemokine receptor 4, has been labeled with a multifunctional single attachment point reagent that contains a DTPA chelate and a fluorescent dye with Cy5.5 spectral properties. Flow cytometry and confocal microscopy showed that the bimodal labeled peptide gave a specific receptor binding that is similar to monofunctionalized peptide derivatives. Therefore, the newly developed bimodal peptide derivative can be used in multimodal imaging applications.

Published
2011

105. Heat‐Induced Radiolabeling of Nanoparticles for Monocyte Tracking by PET

Author

Normandin, Marc D., primary, Yuan, Hushan, additional, Wilks, Moses Q., additional, Chen, Howard H., additional, Kinsella, Joseph M., additional, Cho, Hoonsung, additional, Guehl, Nicolas J., additional, Absi‐Halabi, Nader, additional, Hosseini, Seyed Mohammadreza, additional, El Fakhri, Georges, additional, Sosnovik, David E., additional, and Josephson, Lee, additional

Published
2015
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109. Fluorescent Nanoparticle Uptake for Brain Tumor Visualization1

Author

Tréhin, Rachel, Figueiredo, Jose-Luiz, Pittet, Mikael J, Weissleder, Ralph, Josephson, Lee, and Mahmood, Umar

Subjects
Male, CD11b Antigen, Brain Neoplasms, Green Fluorescent Proteins, Mice, Nude, Carbocyanines, Gliosarcoma, Nanostructures, Rats, Mice, Microscopy, Fluorescence, Cell Line, Tumor, Animals, Humans, Female, Research Article, Fluorescent Dyes
Abstract

Accurate delineation of tumor margins is vital to the successful surgical resection of brain tumors. We have previously developed a multimodal nanoparticle CLIO-Cy5.5, which is detectable by both magnetic resonance imaging and fluorescence, to assist in intraoperatively visualizing tumor boundaries. Here we examined the accuracy of tumor margin determination of orthotopic tumors implanted in hosts with differing immune responses to the tumor. Using a nonuser-based signal intensity method applied to fluorescent micrographs of 9L gliosarcoma green fluorescent protein (GFP) tumors, mean overestimations of 2 and 24 microm were obtained using Cy5.5 fluorescence, compared to the true tumor margin determined by GFP fluorescence, in nude mice and rats, respectively. To resolve which cells internalized the nanoparticle and to quantitate degree of uptake, tumors were disaggregated and cells were analyzed by flow cytometry and fluorescence microscopy. Nanoparticle uptake was seen in both CD11b+ cells (representing activated microglia and macrophages) and tumor cells in both animal models by both methods. CD11b+ cells were predominantly found at the tumor margin in both hosts, but were more pronounced at the margin in the rat model. Additional metastatic (CT26 colon) and primary (Gli36 glioma) brain tumor models likewise demonstrated that the nanoparticle was internalized both by tumor cells and by host cells. Together, these observations suggest that fluorescent nanoparticles provide an accurate method of tumor margin estimation based on a combination of tumor cell and host cell uptake for primary and metastatic tumors in animal model systems and offer potential for clinical translation.

Published
2006

110. DNA-based magnetic nanoparticle assembly acts as a magnetic relaxation nanoswitch allowing screening of DNA-cleaving agents

Author

Perez, J. Manuel, O'Lougin, Terence, Simeone, F. Joseph, Weissleder, Ralph, and Josephson, Lee

Subjects
Gel electrophoresis -- Research, DNA -- Research, Chemistry
Abstract

The study reports the design of a pair of MRS denoting P1 and P2, which are used to detect DNA cleaving, and methylating enzymes. Magnetic relaxation switches (MRS) nanoassemblies act as biosensors for recognition and real-time monitoring of protein based molecule DNA cleaving agents.

Published
2002

114. Optical Imaging of Apoptosis as a Biomarker of Tumor Response to Chemotherapy1

Author

Schellenberger, Eyk A, Bogdanov, Alexei, Petrovsky, Alexander, Ntziachristos, Vasilis, Weissleder, Ralph, and Josephson, Lee

Subjects
Diagnostic Imaging, Mice, Nude, Apoptosis, Phosphatidylserines, Jurkat Cells, Mice, Microscopy, Fluorescence, Drug Resistance, Neoplasm, Biomarkers, Tumor, In Situ Nick-End Labeling, Animals, Humans, Annexin A5, Cyclophosphamide, Neoplasm Transplantation, Research Article
Abstract

A rapid and accurate assessment of the antitumor efficacy of new therapeutic drugs could speed up drug discovery and improve clinical decision making. Based on the hypothesis that most effective antitumor agents induce apoptosis, we developed a near-infrared fluorescent (NIRF) annexin V to be used for optical sensing of tumor environments. To demonstrate probe specificity, we developed both an active (i.e., apoptosisrecognizing) and an inactive form of annexin V with very similar properties (to account for nonspecific tumor accumulation), and tested the agents in nude mice each bearing a cyclophosphamide (CPA) chemosensitive (LLC) and a chemoresistant LLC (CR-LLC). After injection with active annexin V, the tumor-annexin V ratio (TAR; tumor NIRF/background NIRF) for untreated mice was 1.22 ± 0.34 for LLC and 1.43 ± 0.53 for CR-LLC (n = 4). The LLC of CPA-treated mice had significant elevations of TAR (2.56 ± 0.29, P = .001, n = 4), but only a moderate increase was obtained for the CR-LLC (TAR = 1.89 ± 0.19, P = .183). The in vivo measurements correlated well with terminal deoxyribosyl transferasemediated dUTP nick end labeling indexes. When inactive Cy-annexin V was used, with or without CPA treatment and in both CCL and CR-CCL tumors, tumor NIRF values ranged from 0.91 to 1.17 (i.e., tumor were equal to background). We conclude that active Cy-annexin V and surface reflectance fluorescence imaging provide a nonradioactive, semiquantitative method of determining chemosensitivity in LLC xenografts. The method maybe used to image pharmacologic responses in other animal models and, potentially, may permit the clinical imaging of apoptosis with noninvasive or minimally invasive instrumentation.

Published
2003

121. Use of a Single Hybrid Imaging Agent for Integration of Target Validation with In Vivo and Ex Vivo Imaging of Mouse Tumor Lesions Resembling Human DCIS

Author

Buckle, Tessa, primary, Kuil, Joeri, additional, van den Berg, Nynke S., additional, Bunschoten, Anton, additional, Lamb, Hildo J., additional, Yuan, Hushan, additional, Josephson, Lee, additional, Jonkers, Jos, additional, Borowsky, Alexander D., additional, and van Leeuwen, Fijs W. B., additional

Published
2013
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124. The State of Nanoparticle-Based Nanoscience and Biotechnology: Progress, Promises, and Challenges

Author

Pelaz, Beatriz, primary, Jaber, Sarah, additional, de Aberasturi, Dorleta Jimenez, additional, Wulf, Verena, additional, Aida, Takuzo, additional, de la Fuente, Jesús M., additional, Feldmann, Jochen, additional, Gaub, Hermann E., additional, Josephson, Lee, additional, Kagan, Cherie R., additional, Kotov, Nicholas A., additional, Liz-Marzán, Luis M., additional, Mattoussi, Hedi, additional, Mulvaney, Paul, additional, Murray, Christopher B., additional, Rogach, Andrey L., additional, Weiss, Paul S., additional, Willner, Itamar, additional, and Parak, Wolfgang J., additional

Published
2012
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128. An MR Contrast Agent for Intra-Prostatic Imaging of Prostatic Cancer

Author

MASSACHUSETTS GENERAL HOSPITAL BOSTON, Josephson, Lee, MASSACHUSETTS GENERAL HOSPITAL BOSTON, and Josephson, Lee

Abstract

The goal of the current research is the development of a magnetic nanoparticle based MR contrast agent that binds the gastrin releasing peptide receptor, a molecular marker associated with neoplasia. In the first year of this proposed work a series of bombesin derivatives have been synthesized and their binding to the GRP receptor quantitated by displacement of radioiodinated bombesin. Positively charged derivatives have lower LC50s, suggesting that the environment around the binding pocket is negatively charged and hydrophilic. Selected peptides have been conjugated to magnetic nanoparticles with various numbers of peptides per nanoparticle. A non-isotopic, enzyme immunoassay method, based on the ability to quantify fluorescein, has been developed to replace the assay using receptor binding and displacement of radioiodinated peptides.

Published
2004

134. An MR Contrast Agent for Intra-Prostatic Imaging of Prostatic Cancer

Author

MASSACHUSETTS GENERAL HOSPITAL BOSTON, Josephson, Lee, MASSACHUSETTS GENERAL HOSPITAL BOSTON, and Josephson, Lee

Abstract

The goal of the research is to develop a magnetic nanoparticle MR contrast targeted to the gastrin releasing peptide receptor (GRP receptor) that will be used to image the intraprostatic distribution of this key molecular marker. Key accomplishments were: (1) synthesis of a variety peptides interaction with the GRP receptor; (2) demonstration the GRP receptor prefers highly soluble positively charged BN-like peptides; (3) preliminary preparation of peptide-nanoparticle conjugates; (4) development of a FITC based assay.

Published
2003

140. Molecular MRI of Cardiomyocyte Apoptosis With Simultaneous Delayed-Enhancement MRI Distinguishes Apoptotic and Necrotic Myocytes In Vivo

Author

Sosnovik, David E., primary, Garanger, Elisabeth, additional, Aikawa, Elena, additional, Nahrendorf, Matthias, additional, Figuiredo, Jose-Luiz, additional, Dai, Guangping, additional, Reynolds, Fred, additional, Rosenzweig, Anthony, additional, Weissleder, Ralph, additional, and Josephson, Lee, additional

Published
2009
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141. Molecular MRI Detects Low Levels of Cardiomyocyte Apoptosis in a Transgenic Model of Chronic Heart Failure

Author

Sosnovik, David E., primary, Nahrendorf, Matthias, additional, Panizzi, Peter, additional, Matsui, Takashi, additional, Aikawa, Elena, additional, Dai, Guangping, additional, Li, Ling, additional, Reynolds, Fred, additional, Dorn, Gerald W., additional, Weissleder, Ralph, additional, Josephson, Lee, additional, and Rosenzweig, Anthony, additional

Published
2009
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150. Experimental lymph node metastases: enhanced detection with MR lymphography

Author

Weissleder, Ralph, Elizondo, Guillermo, Josephson, Lee, Compton, Carolyn C., Fretz, Christian J., Stark, David D., and Ferrucci, Joseph T.

Subjects
Radiology, Medical -- Research, Tumors -- Measurement, Cancer -- Diagnosis, Metastasis, Health
Abstract

Treatment and prognosis of cancer patients often relies on information obtained from lymph node examination. Magnetic resonance (MR) imaging in conjunction with superparamagnetic (super-magnetized) iron oxide (AMI-25) as a contrast enhancing agent was used to study the spread (metastasis) of lymph node cancer in animal subjects (rats). Metastases often occur in pelvic, abdominal, and mediastinal (a cavity separating two organs) nodes that are difficult to reach via biopsy (removal of a tissue sample from a living human). Contrast-enhanced MR allows measurement of nodal dimensions (e.g., size, volume, shape) to assess the spread of cancer via lymph node metastases. AMI-25 is a lymphographic contrast agent that selectively enhances the internal structure of normal lymph nodes, allowing normal nodes to be differentiated from abnormal nodes (particularly those that are not enlarged). AMI-25 was introduced into the subject rats via injection at various anatomic sites. Intravenous injection, which would have been the best means of introducing the contrast agent was not possible; researchers were aware that contrast agents would have been prevented from reaching lymph nodes by phagocytic cells (attack and destroy foreign matter as part of the immune response in mammals) if the material was administered intravenously. The study found that normal lymph nodes were reliably enhanced by an intramuscular injection of the superparamagnetic agent AMI-25. Lymph node uptake was recorded on MR images two hours after injection. The metastatic tumor-bearing nodes showed less uptake of AMI-25 than did normal nodes. Human studies are needed to perfect the means of detecting minimal amounts of disease, and differentiating hyperplastic (nodes enlarged due to growth of normal tissue) from malignant (cancerous) lymph nodes.

Published
1989

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