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At least 19 recordsLinked to original sources

Exploring the cell's network with molecular imaging.

Molecular imaging is already a powerful tool for investigating molecular interactions within the cell. Interpreting molecular imaging findings will, however, take us into the more unfamiliar, nonlinear realm of networks. The network class of interest is the "scale-free" network, which characterizes not only the cell, but also surprisingly, other real work networks such as the world wide web. This network topology yields insights in how the cell is functionally organized via motifs, modules, and different types of hubs. Additional organizational information is gained from the cell's evolutionary history. Interpretation of molecular images will be deepened by a both qualitative and quantitative knowledge of the cell's network. Importantly, cell network behavior can be independent of molecular detail. For this reason, the same molecule can serve different functions in different cells or even within the same cell. Since a scale-free network's behavior is likely to be nonlinear and exhibit emergent behavior, a degree of caution is prudent in assigning cause and effect to molecular imaging findings in our effort to reengineer some of the cell's functions. Molecular imagers will need to be cognizant of the level of organization in the cell's network they are interrogating.

Amino Acid Motifs↗

[Magnetic resonance tomography: potentials of molecular imaging].

Molecular imaging is "the in-vivo characterization and measurement of biological processes at the cellular and molecular level" and allows the imaging of molecular abnormalities associated with diseases long before morphological changes can be detected. At present, the use of magnetic resonance imaging (MRI) for molecular and cellular imaging is rapidly increasing. MRI is a very attractive candidate, since current MRI protocols already provide anatomic, functional, and biochemical information of excellent image quality and with high spatial resolution. Combining this high spatial resolution/high contrast imaging modality with specific MRI contrast imaging agents for molecular imaging is currently the focus of research in many laboratories worldwide. This paper summarizes the rationale for molecular MRI imaging and describes the basic features of modern molecular imaging strategies with MRI. Finally, a special focus is given to the growing field of applications, e.g., stem cell imaging, imaging of apoptosis, plaques, and other biological targets of interest.

Apoptosis↗

Targeted molecular imaging agents for cellular-scale bimodal imaging.

Molecular imaging is a powerful tool that has the ability to elucidate biochemical mechanisms and signal the early onset of disease. Overexpression of the peripheral benzodiazepine receptor (PBR) has been observed in a variety disease states, including glioblastoma, breast cancer, and Alzheimer's disease. Thus, the PBR could be an attractive target for molecular imaging. In this paper, the authors report cellular uptake and multimodal (MRI and fluorescence) imaging of PBR-overexpressing C6 glioblastoma (brain cancer) cells using a cocktail administration approach and a new PBR targeted lanthanide chelate molecular imaging agent.

Animals↗

[Molecular imaging and molecular guided therapy].

AIM AND METHOD: Scientific publications in the journal of Nuklearmedizin Molecular Imaging and Therapy during 2004/2005 were retrospectively examined for their potential classification to molecular imaging or molecular guided therapy, functional imaging and therapy, and were compared to earlier analyses. RESULTS: Of the 57 original papers examined, 36 (63%) were assigned to the category of molecular imaging/molecular guided therapy. Within this category, the number of original papers on molecular guided therapy increased by 19% compared to preceding periods. There was a general overall increase in the proportion of experimental papers and more frequent inclusion of basic background subjects. CONCLUSION: The development of molecular imaging as a direct instrument in therapy planning leads to further promotion of molecular guided therapy. The structural advantage of nuclear medicine, uniting method-lead diagnosis and therapy within one specialist subject, predestines it to advance molecular imaging and molecular guided therapy.

Humans↗

PET: the merging of biology and imaging into molecular imaging.

PET and SPECT are molecular imaging techniques that use radiolabeled molecules to image molecular interactions of biological processes in vivo. PET imaging technologies have been developed to provide a pathway to the patient from the experimental paradigms of biological and pharmaceutical sciences in genetically engineered and tissue transplanted mouse models of disease. PET provides a novel way for molecular therapies and molecular diagnostics to come together in the discovery of molecules that can be used in low mass amounts to image the function of a target and, by elevating the mass, to pharmacologically modify the function of the target. In both cases, the molecules are the same or analogs of each other. PET can be used to titrate drugs to their sites of action within organ systems in vivo and to assay biological outcomes of the processes being modified in the mouse and the patient. The goal is to provide a novel way to improve the rates of discovery and approval of radiopharmaceuticals and pharmaceuticals. Extending this relationship into clinical practice can improve drug use by providing molecular diagnostics in concert with molecular therapeutics. Diseases are biological processes, and molecular imaging with PET is sensitive and informative to these processes. This sensitivity is exemplified by the detection of disease with PET without evidence of anatomic changes on CT and MRI. These biological changes are seen early in the course of disease, even in asymptomatic stages, as illustrated by the metabolic abnormalities detected with PET and FDG in Huntington's and familial Alzheimer's diseases 7 and 5 y, respectively, before symptoms appear. Differentiation of viable from nonviable tissue is fundamentally a metabolic question, as shown by the use of PET to differentiate patients with coronary artery disease who will benefit from revascularization from those who will not. Although beginning within a specific organ, cancer is a systemic disease the most devastating consequences of which result from metastases. Whole-body PET imaging with FDG enables inspection of glucose metabolism in all organ systems in a single examination to improve the detection and staging of cancer, selection of therapy, and assessment of therapeutic response. In lung and colorectal cancers, melanoma, and lymphoma, PET FDG improves the accuracy of detection and staging from 8% to 43% over conventional work-ups and results in treatment changes in 20%-40% of the patients, depending on the clinical question. Approximately 65% are upstaged because unsuspected metastases are detected, and 35% are downstaged because a structural diagnosis of lesions is changed from malignant to benign. Similar results are now being shown for other cancers. The main difference between CT, sonography, MRI, and PET or SPECT is not technologic but, rather, a difference between detecting and characterizing a disease by its anatomic features as opposed to its biology. The importance and success of developing new molecular imaging probes is increasing as PET becomes integral to the study of the integrative mammalian biology of disease and as molecular therapies targeting the biological processes of disease are developed.

Alzheimer Disease↗

Targeted molecular imaging.

Molecular imaging aims to visualize the cellular and molecular processes occurring in living tissues, and for the imaging of specific molecules in vivo, the development of reporter probes and dedicated imaging equipment is most important. Reporter genes can be used to monitor the delivery and magnitude of therapeutic gene transfer, and the time variation involved. Imaging technologies such as micro-PET, SPECT, MRI and CT, as well as optical imaging systems, are able to non-invasively detect, measure, and report the simultaneous expression of multiple meaningful genes. It is believed that recent advances in reporter probes, imaging technologies and gene transfer strategies will enhance the effectiveness of gene therapy trials.

Animals↗

Neuroimaging and mechanisms of drug abuse: interface of molecular imaging and molecular genetics.

Whereas ligand studies can inform the end-products of dysregulation of genetic expression, reporter gene imaging can provide the means to understand the genetic origin of these end-products. As with radioligand studies, in vivo direct measurement of gene expression will allow genetic processes to be monitored over time in the same subject, use of a subject as his/her own control in intervention studies (i.e., measurement before and after an intervention), and monitoring the spatial distribution of molecular events in the whole brain. Furthermore, reporter gene imaging, by advancing knowledge of the biologic mechanisms of disease states, has important clinical implications, particularly in the development and monitoring of treatments. We expect PET to play a prominent role in the elucidation of substance abuse mechanisms and contribute significantly to the development of innovative treatment strategies.

Brain↗

Molecular imaging perspectives.

Molecular imaging is an emerging technology at the life science/physical science interface which is set to revolutionize our understanding and treatment of disease. The tools of molecular imaging are the imaging modalities and their corresponding contrast agents. These facilitate interaction with a biological target at a molecular level in a number of ways. The diverse nature of molecular imaging requires knowledge from both the life and physical sciences for its successful development and implementation. The aim of this review is to introduce the subject of molecular imaging from both life science and physical science perspectives. However, we will restrict our coverage to the prominent in vivo molecular imaging modalities of magnetic resonance imaging, optical imaging and nuclear imaging. The physical basis of these imaging modalities, the use of contrast agents and the imaging parameters of sensitivity, temporal resolution and spatial resolution are described. Then, the specificity of contrast agents for targeting and sensing molecular events, and some applications of molecular imaging in biology and medicine are given. Finally, the diverse nature of molecular imaging and its reliance on interdisciplinary collaboration is discussed.

Contrast Media↗

Natural language processing and visualization in the molecular imaging domain.

Molecular imaging is at the crossroads of genomic sciences and medical imaging. Information within the molecular imaging literature could be used to link to genomic and imaging information resources and to organize and index images in a way that is potentially useful to researchers. A number of natural language processing (NLP) systems are available to automatically extract information from genomic literature. One existing NLP system, known as BioMedLEE, automatically extracts biological information consisting of biomolecular substances and phenotypic data. This paper focuses on the adaptation, evaluation, and application of BioMedLEE to the molecular imaging domain. In order to adapt BioMedLEE for this domain, we extend an existing molecular imaging terminology and incorporate it into BioMedLEE. BioMedLEE's performance is assessed with a formal evaluation study. The system's performance, measured as recall and precision, is 0.74 (95% CI: [.70-.76]) and 0.70 (95% CI [.63-.76]), respectively. We adapt a JAVA viewer known as PGviewer for the simultaneous visualization of images with NLP extracted information.

Animals↗

Present and future capabilities of molecular imaging techniques to understand brain function.

This article focuses on the use of positron emitting tracers and positron emission tomography (PET) as the most specific and sensitive means for imaging molecular interactions and pathways within the human brain. The concept of the imaging science of PET is developed whereby the key components that contribute to the overall accuracy of the image of molecular activity need to be separately optimized. These include radiolabelling of tracer molecules and ligands with radioisotopes of short radioactive half-life, the search for specific radioligands and tracers, and hence the need to mine molecular databases for molecules suitable for in-vivo imaging. The sensitivity and accuracy of PET scanners need to be advanced along with improvements in the signal-to-noise ratio of the tomographic reconstruction algorithms. Finally, the models used for the analysis of serial time frames of kinetic data need to be developed, the operation of which have to be effected with the minimum of noise propagation. The future use of PET for drug discovery and development is discussed whereby it offers proof principle for assays of in-vivo expression of therapeutic molecular targets as accessed from the blood stream; tissue pharmacokinetics of novel compounds; degree of occupancy of molecular targets; and pharmacodynamic measures of drug action. The future application of PET rests heavily on drug discoverers contributing to discovering specific PET radioligands and tracers in order to provide these assays through in-vivo molecular imaging.

Algorithms↗

Natural language processing in the molecular imaging domain.

Molecular imaging represents the intersection between imaging and genomic sciences. There has been a surge in research literature and information in both sciences. Information contained within molecular imaging literature could be used to 1) link to genomic and imaging information resources and 2) to organize and index images. This research focuses on the adaptation, evaluation, and application of BioMedLEE, a natural language processing system (NLP), in the automated extraction of information from molecular imaging abstracts.

Cell Line↗

Small animal SPECT and its place in the matrix of molecular imaging technologies.

Molecular imaging refers to the use of non-invasive imaging techniques to detect signals that originate from molecules, often in the form of an injected tracer, and observe their interaction with a specific cellular target in vivo. Differences in the underlying physical principles of these measurement techniques determine the sensitivity, specificity and length of possible observation of the signal, characteristics that have to be traded off according to the biological question under study. Here, we describe the specific characteristics of single photon emission computed tomography (SPECT) relative to other molecular imaging technologies. SPECT is based on the tracer principle and external radiation detection. It is capable of measuring the biodistribution of minute (<10(-10) molar) concentrations of radio-labelled biomolecules in vivo with sub-millimetre resolution and quantifying the molecular kinetic processes in which they participate. Like some other imaging techniques, SPECT was originally developed for human use and was subsequently adapted for imaging small laboratory animals at high spatial resolution for basic and translational research. Its unique capabilities include (i) the ability to image endogenous ligands such as peptides and antibodies due to the relative ease of labelling these molecules with technetium or iodine, (ii) the ability to measure relatively slow kinetic processes (compared with positron emission tomography, for example) due to the long half-life of the commonly used isotopes and (iii) the ability to probe two or more molecular pathways simultaneously by detecting isotopes with different emission energies. In this paper, we review the technology developments and design tradeoffs that led to the current state-of-the-art in SPECT small animal scanning and describe the position SPECT occupies within the matrix of molecular imaging technologies.

Animals↗

Relationships between radiotracer properties and image quality in molecular imaging of the brain with positron emission tomography.

In molecular imaging of the brain, many factors affect the reliability of the quantitative information that can be derived from the imaging process. This article discusses factors impacting on the imaging quality that are related to the radiotracer per se. Following a brief summary of key concepts in receptor quantification, a number of these factors are discussed, including selectivity, affinity, delivery, and lipophilicity. Concepts discussed in the theoretical section are then illustrated, by reviewing a recent comparative evaluation of four agents developed to label the serotonin transporter ([(11)C]ADAM, [(11)C]DASB, [(11)C]DAPA, and [(11)C]AFM). Specifically, the relationship between affinity and lipophilicity, measured in vitro, and several scanning parameters are investigated. These include peripherical metabolism, brain uptake, required scanning time, nonspecific binding, and binding potential. It is shown that, within a given structural family, affinity and lipophilicity are associated with scan outcome in a relatively predictable manner.

Animals↗