Molecular Imaging in Drug Discovery and Development

被引:29
作者
Lindner, Jonathan R. [1 ,2 ]
Link, Jeanne [3 ]
机构
[1] Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA
[2] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA
[3] Oregon Hlth & Sci Univ, Ctr Radiol Res, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA
基金
美国国家卫生研究院;
关键词
cardiovascular agents; drug approval; drug discovery; molecular imaging; molecular medicine; POSITRON-EMISSION-TOMOGRAPHY; EXPERIMENTAL MYOCARDIAL-INFARCTION; STEM-CELL THERAPY; MAGNETIC-RESONANCE; CARDIOVASCULAR-DISEASE; ATHEROSCLEROTIC PLAQUE; VASCULAR INFLAMMATION; HEART-FAILURE; ANNEXIN A5; IRON-OXIDE;
D O I
10.1161/CIRCIMAGING.117.005355
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Noninvasive imaging has played an increasing role in the process of cardiovascular drug development. This review focuses specifically on the use of molecular imaging, which has been increasingly applied to improve and accelerate certain preclinical steps in drug development, including the identification of appropriate therapeutic targets, evaluation of on-target and off-target effects of candidate therapies, assessment of dose response, and the evaluation of drug or biological biodistribution and pharmacodynamics. Unlike the case in cancer medicine, in cardiovascular medicine, molecular imaging has not been used as a primary surrogate clinical end point for drug approval. However, molecular imaging has been applied in early clinical trials, particularly in phase 0 studies, to demonstrate proof-of-concept or to explain variation in treatment effect. Many of these applications where molecular imaging has been used in drug development have involved the retasking of technologies that were originally intended as clinical diagnostics. With greater experience and recognition of the rich information provided by in vivo molecular imaging, it is anticipated that it will increasingly be used to address the enormous time and costs associated with bringing a new drug to clinical launch.
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收藏
页数:11
相关论文
共 73 条
[1]   Multimodality molecular imaging identifies proteolytic and osteogenic activities in early aortic valve disease [J].
Aikawa, Elena ;
Nahrendorf, Matthias ;
Sosnovik, David ;
Lok, Vincent M. ;
Jaffer, Farouc A. ;
Aikawa, Masanori ;
Weissleder, Ralph .
CIRCULATION, 2007, 115 (03) :377-386
[2]   Molecular imaging of endothelial vascular cell adhesion molecule-1 expression and inflammatory cell recruitment during vasculogenesis and ischemia-mediated arteriogenesis [J].
Behm, Carolyn Z. ;
Kaufmann, Beat A. ;
Carr, Chad ;
Lankford, Miles ;
Sanders, John M. ;
Rose, C. Edward ;
Kaul, Sanjiv ;
Lindner, Jonathan R. .
CIRCULATION, 2008, 117 (22) :2902-2911
[3]   Cardiac Positron Emission Tomography Enhances Prognostic Assessments of Patients With Suspected Cardiac Sarcoidosis [J].
Blankstein, Ron ;
Osborne, Michael ;
Naya, Masanao ;
Waller, Alfonso ;
Kim, Chun K. ;
Murthy, Venkatesh L. ;
Kazemian, Pedram ;
Kwong, Raymond Y. ;
Tokuda, Michifumi ;
Skali, Hicham ;
Padera, Robert ;
Hainer, Jon ;
Stevenson, William G. ;
Dorbala, Sharmila ;
Di Carli, Marcelo F. .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2014, 63 (04) :329-336
[4]   Myocardial substrate and route of administration determine acute cardiac retention and lung bio-distribution of cardiosphere-derived cells [J].
Bonios, Michael ;
Terrovitis, John ;
Chang, Connie Y. ;
Engles, James M. ;
Higuchi, Takahiro ;
Lautamaeki, Riikka ;
Yu, Jianhua ;
Fox, James ;
Pomper, Martin ;
Wahl, Richard L. ;
Tsui, Benjamin M. ;
O'Rourke, Brian ;
Bengel, Frank M. ;
Marban, Eduardo ;
Abraham, M. Roselle .
JOURNAL OF NUCLEAR CARDIOLOGY, 2011, 18 (03) :443-450
[5]   Molecular Imaging of Aortic Aneurysms [J].
Buxton, Denis B. .
CIRCULATION-CARDIOVASCULAR IMAGING, 2012, 5 (03) :392-399
[6]   Dysregulated Selectin Expression and Monocyte Recruitment During Ischemia-Related Vascular Remodeling in Diabetes Mellitus [J].
Carr, Chad L. ;
Qi, Yue ;
Davidson, Brian ;
Chadderdon, Scott ;
Jayaweera, Ananda R. ;
Belcik, J. Todd ;
Benner, Cameron ;
Xie, Aris ;
Lindner, Jonathan R. .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2011, 31 (11) :2526-U415
[7]   Cardiac Sympathetic Imaging With mIBG in Heart Failure [J].
Carrio, Ignasi ;
Cowie, Martin R. ;
Yamazaki, Junichi ;
Udelson, James ;
Camici, Paolo G. .
JACC-CARDIOVASCULAR IMAGING, 2010, 3 (01) :92-100
[8]   Proinflammatory Endothelial Activation Detected by Molecular Imaging in Obese Nonhuman Primates Coincides With Onset of Insulin Resistance and Progressively Increases With Duration of Insulin Resistance [J].
Chadderdon, Scott M. ;
Belcik, J. Todd ;
Bader, Lindsay ;
Kirigiti, Melissa A. ;
Peters, Dawn M. ;
Kievit, Paul ;
Grove, Kevin L. ;
Lindner, Jonathan R. .
CIRCULATION, 2014, 129 (04) :471-478
[9]   Molecular imaging: The key to advancing cardiac stem cell therapy [J].
Chen, Ian Y. ;
Wu, Joseph C. .
TRENDS IN CARDIOVASCULAR MEDICINE, 2013, 23 (06) :201-210
[10]   Molecular Imaging in Atherosclerosis, Thrombosis, and Vascular Inflammation [J].
Choudhury, Robin P. ;
Fisher, Edward A. .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2009, 29 (07) :983-991