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R Weissleder

Publications and source records attributed to R Weissleder.

At least 19 recordsLinked to original sources
PubMed2007

[Cell tracking. Principles and applications].

Cell based therapies such as stem cell therapies or adoptive immunotherapies are currently being explored as a potential treatment for a variety of diseases such as Parkinson's disease, diabetes or cancer. However, quantitative and qualitative evaluation of adoptively transferred cells is indispensable for monitoring the efficiency of the treatment. Current approaches mostly analyze transferred cells from peripheral blood, which cannot assess whether transferred cells actually home to and stay in the targeted tissue. Using cell-labeling methods such as direct labeling or transfection with a marker gene in conjunction with various imaging modalities (MRI, optical or nuclear imaging), labeled cells can be followed in vivo in real-time, and their accumulation as well as function in vivo can be monitored and quantified accurately. This method is usually referred to as "cell tracking" or "cell trafficking" and is also being applied in basic biological sciences, exemplified in the evaluation of genes contributing to metastasis. This review focuses on principles of this promising methodology and explains various approaches by highlighting recent examples.

Cell Separation↗
PubMed2007

[Advances in cardiovascular medicine through molecular imaging].

We will witness a change of paradigm in cardiovascular imaging, which is empowered by advances in imaging technology, biochemistry, molecular biology and nanotechnology. Instead of simply following the physical distribution of established contrast agents, we now have the opportunity to noninvasively image biological processes such as enzyme activity, interaction with cell surface markers, gene expression and cell migration. These advancements open up new avenues in basic cardiovascular research and will greatly speed up the pace of discovery. Patient management will profit as well: cardiovascular molecular imaging will strengthen personlized and prophylactic medicine through timely and precise diagnostics. In our review we describe selected molecular imaging strategies in atherosclerosis, myocardial ischemia and healing.

Animals↗
PubMed2005

Mouse models of human non-small-cell lung cancer: raising the bar.

Lung cancer is a devastating disease that presents a challenge to basic research to provide new steps toward therapeutic advances. The cell-type-specific responses to oncogenic mutations that initiate and regulate lung cancer remain poorly defined. A better understanding of the relevant signaling pathways and mechanisms that control therapeutic outcome could also provide new insight. Improved conditional mouse models are now available as tools to improve the understanding of the cellular and molecular origins of adenocarcinoma. These models have already proven their utility in proof-of-principle experiments with new technologies including genomics and imaging. Integrated thinking to apply technological advances while using the appropriate mouse model is likely to facilitate discoveries that will significantly improve lung cancer detection and intervention.

Animals↗
PubMed2004

Measurement of tumor interstitial volume fraction: method and implication for drug delivery.

It is important to evaluate the tumor interstitial volume fraction that is accessible for drug accumulation during the distribution phase in order to determine the potential efficacy of cancer chemotherapy. In this study, we performed simulations of magnetic resonance imaging (MRI) signal intensity using a two-compartment tissue model for quantitative analyses of absolute interstitial volume measurements while we experimentally characterized a mouse tumor model with a dual MR contrast-agent method. Previously, consecutive intravenous injections of a strictly intravascular T1 contrast agent followed by an extravasating agent were used as a strategy for the quantification of both relative blood volume (Rel_BV) and relative interstitial volume (Rel_ITST) (Weissleder et al. Eur J Cancer 1998;34:1448-1454; Bogdanov et al. Neoplasia 1991;1:438-435). In the current study, we demonstrate that this approach can be further improved, and that it enables one to accurately evaluate both relative and absolute interstitial volumes. The animal data indicated that a significant difference exists between the absolute interstitial volume fractions of subcutaneously implanted MDA PCa 2b tumor and skeletal muscle tissue (27.5 +/- 9.1% and 15.9 +/- 0.7%, respectively (P < 0.05)), while only a minor difference was found for the absolute blood volumes (Abs_BV) (Kim et al. Magn Reson Med 2002;47:1110-1120) of these tissues.

Animals↗
PubMed2004

Molecular imaging of gene therapy for cancer.

Gene therapy of cancer has been one of the most exciting and elusive areas of scientific and clinical research in the past decade. One of the most critical issues for ensuring success of this therapy is the development of technology for noninvasive monitoring of the location, magnitude and duration of vector-mediated gene expression, as well as the distribution and targeting of vector particles in vivo. In recent years many advances have been made in high-resolution, in vivo imaging methods, including: radionuclide imaging, such as positron emission tomography (PET) and single photon emission tomography (SPECT), magnetic resonance (MR) imaging and spectroscopy, bioluminescence imaging and various fluorescence imaging techniques, including fluorescence-mediated tomography (FMT) and near-infrared fluorescence (NIRF) reflectance imaging. A variety of factors determine the choice of specific imaging system, some of them are the imaging requirements (single or repeated), intended use (animal or human) and spatial requirements (organs versus cellular resolution and depth). This review provides descriptions of modalities applicable to imaging different parameters of vector-mediated gene expression in tumors and stem cell tracking in vivo.

Animals↗
PubMed2004

Fluorescence molecular imaging of small animal tumor models.

In vivo imaging of molecular events in small animals has great potential to impact basic science and drug development. For this reason, several imaging technologies have been adapted to small animal research, including X-ray, magnetic resonance, and radioisotope imaging. Despite this plethora of visualization techniques, fluorescence imaging is emerging as an important alternative because of its operational simplicity, safety, and cost-effectiveness. Fluorescence imaging has recently become particularly interesting because of advances in fluorescent probe technology, including targeted fluorochromes as well as fluorescent "switches" sensitive to specific biochemical events. While past biological investigations using fluorescence have focused on microscopic examination of ex vivo, in vitro, or intravital specimens, techniques for macroscopic fluorescence imaging are now emerging for in vivo molecular imaging applications. This review illuminates fluorescence imaging technologies that hold promise for small animal imaging. In particular we focus on planar illumination techniques, also known as Fluorescence Reflectance Imaging (FRI), and discuss its performance and current use. We then discuss fluorescence molecular tomography (FMT), an evolving technique for quantitative three-dimensional imaging of fluorescence in vivo. This technique offers the promise of non-invasively quantifying and visualizing specific molecular activity in living subjects in three dimensions.

Animals↗
PubMed2004

Illuminating the dynamics of intracellular activity with 'active' molecular reporters.

Traditionally, fluorescent and luminescent reporter proteins have been used as indicators of gene expression and protein localization. However, insightful mutagenesis and protein engineering strategies have transformed these simple passive reporters into active biological sensors. Molecular reporters are now being designed to alter their intrinsic optical properties in response to specific biomolecular interactions. Applications for these novel biological sensors range from monitoring intracellular pH and ion fluxes to detecting protein-protein interactions and enzymatic activity. The ability to monitor the dynamics of intracellular activity in response to external stimuli can help elucidate the cascade of events involved in complex processes such as mechanotransduction. Here we review some of the approaches used to create these novel biological sensors, including resonance energy transfer (RET) between reporter proteins and protein fragmentation strategies.

Fluorescence Resonance Energy Transfer↗
PubMed2002

Targeting of MPEG-protected polyamino acid carrier to human E-selectin in vitro.

Targeted diagnostic agents are expected to have a significant impact in molecular imaging of cell-surface associated markers of proliferation, inflammation and angiogenesis. In this communication, we describe a new class of targeted polyamino acid-based protected graft copolymers (PGC) of poly-(L-lysine) and methyl poly-(ethylene glycol) (PGC) covalently conjugated with a monoclonal antibody fragment, F(ab')(2). We utilized targeted PGC conjugates as carriers of near-infrared indocyanine fluorophores (Cy5.5) for optical imaging of endothelial cell populations expressing IL-1 beta inducible proinflammatory marker E-selectin. We compared two conjugation chemistries, involving either introduction of sulfhydryl group to F(ab')(2), or via direct attachment of the antibody fragment directly to the chemically activated PGC. Both PGC-based targeted agents demonstrated high binding specificity (20-30 fold over non-specific uptake) and were utilized for imaging E-selectin expression on human endothelial cells activated with IL-1 beta.

Amino Acids↗
PubMed2001

Normal T-cell response and in vivo magnetic resonance imaging of T cells loaded with HIV transactivator-peptide-derived superparamagnetic nanoparticles.

The present study analyzed the feasibility of using magnetic resonance imaging (MRI) to monitor T-cell homing in vivo after loading T cells with superparamagnetic iron oxide (CLIO) nanoparticles derivatized with a peptide sequence from the transactivator protein (Tat) of HIV-1. T cells were isolated from C57BL/6 (B6) mice and loaded with 0, 400, 800, 1600, or 8000 ng/ml of FITC conjugated CLIO-Tat (FITC-CLIO-Tat). There was a dose-dependent uptake of FITC-CLIO-Tat by T cells. Stimulation of FITC-CLIO-Tat loaded T cells with anti-CD3 (0.1 microg/ml) plus IL-2 (5 ng/ml) elicited normal activation and activation-induced cell death (AICD) responses, and normal upregulation of CD69, ICAM-1 (CD54), L-selectin (CD62L), and Fas. The FITC-CLIO-Tat loaded T cells (3 x 10(7)) were transferred intravenously (i.v.) into B6 mice and the in vivo MRI of mice was acquired using a spin-echo pulse sequence at 4.7 T with a Bruker Biospec system. Homing of T cells into the spleen was observed by a decrease in MRI signal intensity within 1 h after the transfer, which remained decreased for 2-24 h after transfer. These homing data were confirmed by FACS analysis and biodistribution analysis using 125I-CLIO-Tat. Thus, T cells can be efficiently loaded with FITC-CLIO-Tat without interfering with their normal activation and AICD, or homing to the spleen, and the biodistribution of FITC-CLIO-Tat loaded T cells can be monitored in vivo over time by MRI.

Animals↗
PubMed2001

[Molecular imaging in magnetic resonance tomography and nuclear medicine].

The identification of genetic and biochemical changes allows a more conclusive characterization and classification of disease. Up to now this information is mostly obtained through in vitro analysis after resection or biopsy by immunohistopathology and molecular biology. There is a definite need for non-invasive detection and repeated monitoring of such changes in experimental research as well as in clinical trials. Therefore, it is necessary to develop radiological imaging techniques that not only visualize morphologic and physiologic alterations, but track genetic and biochemical processes. This short review reports some of the various ongoing research projects that address this problem and provide some very promising approaches.

Animals↗
PubMed2001

[Experimental and clinical approaches to lymph node imaging].

Exact assessment of lymph nodes is crucial to tumor staging, choice of therapy and in predicting the outcome. Although imaging plays a central role in the evaluation of lymph nodes, current imaging methods have low sensitivity and specificity primarily because they rely on insensitive morphological criteria or because they have low special resolution. Because of this diagnostic dilemma invasive, expansive and uncomfortable diagnostic techniques and/or unnecessary aggressive therapies are still in use. This brief overview is intended to summarize current imaging strategies and to give an outlook on experimental and clinical strategies in lymph node imaging in cancer.

Animals↗
PubMed2001

[Progress in optical imaging].

Different optical imaging technologies have significantly progressed over the last years. Besides advances in imaging techniques and image reconstruction, new "smart" optical contrast agents have been developed which can be used to detect molecular targets (such as endogenous enzymes) in vivo. The combination of novel imaging technologies coupled with smart agents bears great diagnostic potential both clinically and experimentally. This overview outlines the basic principles of optical imaging and summarizes the current state of the art.

Animals↗
PubMed2001

[Imaging of angiogenesis].

Angiogenesis of tumors has gained tremendous attention in the research community over the last years. Novel anti-angiogenic treatment protocols are currently in various phases of clinical testing. Thus, the major challenge for Radiological diagnostics is to develop imaging methods which reliably measure the angiogenic tumor burden as well as tumor response to anti-angiogenic treatment in vivo. This article intends to provide a brief overview of imaging strategies for angiogenesis and anti-angiogenic treatment.

Angiogenesis Inhibitors↗
PubMed2001

In vivo imaging of gene and cell therapies.

Molecular imaging can be broadly defined as the in vivo characterization and measurement of biological processes at the cellular and molecular level. In contrast to commonly used clinical imaging, it sets forth to probe the molecular abnormalities that are the basis of disease, rather than imaging the end effects of these molecular alterations. Development of new imaging technologies requires a multidisciplinary collaboration between biologists, chemists, physicists, and imaging scientists to create novel agents, signal amplification strategies, and imaging techniques that successfully address these questions. In this article we attempt to present some of the recent developments and show how molecular imaging can be used, at least experimentally, to assess specific molecular targets for gene- and cell-based therapies. In particular, we place emphasis on the development and use of experimental small-animal models, which are particularly inclined toward this approach, primarily in combination with magnetic resonance (MR), radionuclide, and optical imaging. In the future, specific imaging of disease targets will allow earlier detection and characterization of disease, as well as earlier and direct molecular assessment of treatment efficacy.

Animals↗