In vivo small animal imaging: Current status and future prospects George C. Kagadis a Department of Medical Physics, School of Medicine, University of Patras, P.O. BOX 132 73, GR 265 04 Rion, Greece and Department of Radiology, Mayo Clinic, Rochester, Minnesota 55905 George Loudos Department of Medical Instruments Technology, Technological Educational Institute of Athens, 28 Ag. Spyridonos Street, GR 122 10 Egaleo, Greece Konstantinos Katsanos Department of Radiology, School of Medicine, University of Patras, GR 265 04 Rion, Greece Steve G. Langer Department of Radiology, Mayo Clinic, Rochester, Minnesota 55905 George C. Nikiforidis Department of Medical Physics, School of Medicine, University of Patras, GR 265 04 Rion, Greece Received 4 July 2010; revised 13 October 2010; accepted for publication 20 October 2010; published 24 November 2010 The use of small animal models in basic and preclinical sciences constitutes an integral part of testing new pharmaceutical agents prior to commercial translation to clinical practice. Whole-body small animal imaging is a particularly elegant and cost-effective experimental platform for the timely validation and commercialization of novel agents from the bench to the bedside. Biomedical imaging is now listed along with genomics, proteomics, and metabolomics as an integral part of biological and medical sciences. Miniaturized versions of clinical diagnostic modalities, including but not limited to microcomputed tomography, micromagnetic resonance tomography, microsingle- photon-emission tomography, micropositron-emission tomography, optical imaging, digital angiog- raphy, and ultrasound, have all greatly improved our investigative abilities to longitudinally study various experimental models of human disease in mice and rodents. After an exhaustive literature search, the authors present a concise and critical review of in vivo small animal imaging, focusing on currently available modalities as well as emerging imaging technologies on one side and mo- lecularly targeted contrast agents on the other. Aforementioned scientific topics are analyzed in the context of cancer angiogenesis and innovative antiangiogenic strategies under-the-way to the clinic. Proposed hybrid approaches for diagnosis and targeted site-specific therapy are highlighted to offer an intriguing glimpse of the future. © 2010 American Association of Physicists in Medicine. DOI: 10.1118/1.3515456 Key words: small animal imaging, molecular imaging, micro-SPECT, micro-PET, micro-CT, micro-MRI, digital angiography, optical imaging, ultrasound, hybrid imaging I. INTRODUCTION The use of small animal models in basic and preclinical sci- ences constitutes an integral part of testing new pharmaceu- tical agents prior to commercial translation to clinical practice. 1,2 Nowadays, owing to the development of gene knockout and transgenic techniques, small animals such as mice and other rodents are widely used for experimental modeling in preclinical studies of cardiovascular and neo- plastic disorders. 3,4 Whole-body small animal imaging is a particularly elegant and cost-effective experimental platform for the timely validation and commercialization of novel agents from the bench to the bedside. On average, $800 mil- lion and 12 years of research are spent for the successful translation of an experimental compound to human therapy. Only 1 out of 1000 agents tested enter preclinical research and approximately only 1 out of 5000 make it from the bench to the bedside. 5,6 Preclinical animal imaging is thus of crucial importance in the majority of stages of new drug discovery and development, contributing to high-throughput phenotyping of transgenic animals, profiling of new disease models, pharmacological and pharmacokinetic analysis for target identification, and safety testing and evaluation of drug-effects on host anatomy, function, and metabolism. 7,8 Imaging is now listed along with genomics, proteomics, and metabolomics as a part of the more general “biomarker con- cept.” Biomarkers are objectively measured, quantitative pa- rameters of normal and abnormal biological processes that serve as indicative end points guiding safety and efficacy of an experimental compound for potential drug development. 7 For example, noninvasive radiological imaging permits evaluation of toxic side-effects on target organs longitudi- nally in vivo or postmortem without invasive and labor in- tensive tissue dissection, fixation, and sectioning. 1,9 Miniaturized versions of clinical diagnostic modalities, such as micropositron-emission tomography micro-PET, microsingle-photon-emission tomography micro-SPECT, 6421 6421 Med. Phys. 37 „12…, December 2010 0094-2405/2010/37„12…/6421/22/$30.00 © 2010 Am. Assoc. Phys. Med.