TY  - JOUR
AB  - Optical imaging has seen significant developments over the past decade as an investigational tool for in-vivo visualization of cellular and sub-cellular events. With the recent addition of optoacoustic (photoacoustic) methods, in particular multi-spectral opto-acoustic tomography (MSOT), to the already rich armamentarium of photonic methods the capacity of optical molecular imaging across scales has widened significantly. MSOT brings unique features into optical imaging, namely high resolution optical imaging over several millimeters to centimeters of tissue depth and the ability to simultaneously resolve multiple tissue molecules and extrinsically administered optical or optoacoustic agents with physiological or molecular specificity. Here, we discuss the implications of utilizing MSOT in the context of drug discovery and review suitable optoacoustic agents against disease and drug efficacy biomarkers. The combination of existing knowledge on generating optical targeted contrast, with the high resolution deep tissue visualization offered by MSOT, allows for the development of next-generation biological optical imaging and corresponding drug discovery applications.
AU  - Bednar, B.*
AU  - Ntziachristos, V.
C1  - 8622
C2  - 30268
SP  - 2117-2127
TI  - Opto-acoustic imaging of drug discovery biomarkers.
JO  - Curr. Pharm. Biotechnol.
VL  - 13
IS  - 11
PB  - Bentham Science 
PY  - 2012
SN  - 1389-2010
ER  - 

TY  - JOUR
AB  - For centuries, biological discoveries were based on optical imaging, in particular microscopy but also several chromophoric assays and photographic approaches. With the recent emergence of methods appropriate for bio-marker in vivo staining, such as bioluminescence, fluorescent molecular probes and proteins, as well as nanoparticle-based targeted agents, significant attention has been shifted toward in vivo interrogations of different dynamic biological processes at the molecular level. This progress has been largely supported by the development of advanced tomographic imaging technologies suitable for obtaining volumetric visualization of bio-marker distributions in small animals at a whole-body or whole-organ scale, an imaging frontier that is not accessible by the existing tissue-sectioning microscopic techniques due to intensive light scattering beyond the depth of a few hundred microns. Major examples of such recently developed optical imaging modalities are reviewed here, including bioluminescence tomography (BLT), fluorescence molecular tomography (FMT), and optical projection tomography (OPT). The pharmaceutical imaging community has quickly appropriated itself of these novel forms of optical imaging, since they come with very compelling advantages, such as quantitative three-dimensional capabilities, direct correlation to the biological cultures, easiness and cost-effectiveness of use, and the use of safe non-ionizing radiation. Some multi-modality approaches, combining light with other imaging modalities such as X-Ray CT or MRI, giving the ability to acquire both an optical contrast reconstruction along with a hi-fidelity anatomical images, are also reviewed. A separate section is devoted to the hybrid imaging techniques based on the optoacoustic phenomenon, such as multispectral optoacoustic tomography (MSOT), which are poised to leverage the traditional contrast and specificity advantages of optical spectrum by delivering an ever powerful set of capabilities, including real-time operation and high spatial resolution, not affected by the scattering nature of biological tissues.
AU  - Razansky, D.
AU  - Deliolanis, N.
AU  - Vinegoni, C.*
AU  - Ntziachristos, V.
C1  - 7127
C2  - 29513
SP  - 504-522
TI  - Deep tissue optical and optoacoustic molecular imaging technologies for small animal research and drug discovery.
JO  - Curr. Pharm. Biotechnol.
VL  - 13
IS  - 4
PB  - Bentham Science Publishers
PY  - 2012
SN  - 1389-2010
ER  - 

TY  - JOUR
AB  - The German Mouse Clinic (GMC) is a large scale phenotyping center where mouse mutant lines are analyzed in a standardized and comprehensive way. The result is an almost complete picture of the phenotype of a mouse mutant line - a systemic view. At the GMC, expert scientists from various fields of mouse research work in close cooperation with clinicians side by side at one location. The phenotype screens comprise the following areas: allergy, behavior, clinical chemistry, cardiovascular analyses, dysmorphology, bone and cartilage, energy metabolism, eye and vision, hostpathogen interactions, immunology, lung function, molecular phenotyping, neurology, nociception, steroid metabolism, and pathology. The German Mouse Clinic is an open access platform that offers a collaboration-based phenotyping to the scientific community (www.mouseclinic.de). More than 80 mutant lines have been analyzed in a primary screen for 320 parameters, and for 95% of the mutant lines we have found new or additional phenotypes that were not associated with the mouse line before. Our data contributed to the association of mutant mouse lines to the corresponding human disease. In addition, the systemic phenotype analysis accounts for pleiotropic gene functions and refines previous phenotypic characterizations. This is an important basis for the analysis of underlying disease mechanisms. We are currently setting up a platform that will include environmental challenge tests to decipher genome-environmental interactions in the areas nutrition, exercise, air, stress and infection with different standardized experiments. This will help us to identify genetic predispositions as susceptibility factors for environmental influences.
AU  - Fuchs, H.
AU  - Gailus-Durner, V.
AU  - Adler, T.*
AU  - Aguilar-Pimentel, J.A.*
AU  - Becker, L.*
AU  - Bolle, I.
AU  - Brielmeier, M.
AU  - Calzada-Wack, J.
AU  - Dalke, C.
AU  - Ehrhardt, N.*
AU  - Fasnacht, N.*
AU  - Ferwagner, B.
AU  - Frischmann, U.*
AU  - Hans, W.
AU  - Hölter, S.M.
AU  - Hölzlwimmer, G.
AU  - Horsch, M.
AU  - Javaheri, A.*
AU  - Kallnik, M.
AU  - Kling, E.*
AU  - Lengger, C.
AU  - Maier, H.
AU  - Mossbrugger, I.
AU  - Mörth, C.*
AU  - Naton, B.
AU  - Nöth, U.
AU  - Pasche, B.*
AU  - Prehn, C.
AU  - Przemeck, G.K.H.
AU  - Puk, O.
AU  - Rácz, I.*
AU  - Rathkolb, B.*
AU  - Rozman, J.*
AU  - Schäble, K.-H.
AU  - Schreiner, R.*
AU  - Schrewe, A.*
AU  - Sina, C.*
AU  - Steinkamp, R.
AU  - Thiele, F.
AU  - Willershäuser, M.
AU  - Zeh, R.M.
AU  - Adamski, J.
AU  - Busch, D.H.*
AU  - Beckers, J.
AU  - Behrendt, H.*
AU  - Daniel, H.*
AU  - Esposito, I.
AU  - Favor, J.
AU  - Graw, J.
AU  - Heldmaier, G.*
AU  - Höfler, H.
AU  - Ivandic, B.*
AU  - Katus, H.A.*
AU  - Klingenspor, M.*
AU  - Klopstock, T.*
AU  - Lengeling, A.*
AU  - Mempel, M.*
AU  - Müller, W.*
AU  - Neschen, S.
AU  - Ollert, M.*
AU  - Quintanilla-Martinez, L.
AU  - Rosenstiel, P.*
AU  - Schmidt, J.
AU  - Schreiber, S.*
AU  - Schughart, K.*
AU  - Schulz, S.
AU  - Wolf, E.*
AU  - Wurst, W.
AU  - Zimmer, A.*
AU  - Hrabě de Angelis, M.
C1  - 1112
C2  - 26084
SP  - 236-243
TI  - The German Mouse Clinic: A platform for systemic phenotype analysis of mouse models.
JO  - Curr. Pharm. Biotechnol.
VL  - 10
IS  - 2
PB  - Bentham
PY  - 2009
SN  - 1389-2010
ER  - 

TY  - JOUR
AB  - Aim of this review is to demonstrate the relevance of animal models created by ENU mutagenesis for the pharmaceutical community to understand diseases and the modulation of disease status by pharmaceutical compounds. We give an overview of what ENU mutagenesis in mice implies and introduce the main research centers running ENU mutagenesis projects. The different strategies of ENU mutagenesis screens are explained as well as the latest advances in mapping and mutation detection strategies, which until recently have been the main limiting step in forward genetics/phenotype- driven approaches. ENU mutagenesis in mice has shown its power by providing animal models for human monogenic diseases. Moreover, the development of modifier and sensitized screens extended this resource to models for multigenic diseases and thereby opened the perspective to understand the modulation of disease states. Finally, we provide information about the accessibility and availability of these models for academic research.
AU  - Soewarto, D.*
AU  - Klaften, M.
AU  - Rubio-Aliaga, I.*
C1  - 1035
C2  - 26085
SP  - 198-213
TI  - Features and strategies of ENU mouse mutagenesis.
JO  - Curr. Pharm. Biotechnol.
VL  - 10
IS  - 2
PB  - Bentham
PY  - 2009
SN  - 1389-2010
ER  -