PET/SPECT imaging of hindlimb ischemia: focusing on angiogenesis and blood flow
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REVIEW PAPER
PET/SPECT imaging of hindlimb ischemia: focusing on angiogenesis and blood flow Hakan Orbay • Hao Hong • Yin Zhang Weibo Cai
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Received: 17 September 2012 / Accepted: 22 October 2012 / Published online: 2 November 2012 Ó Springer Science+Business Media Dordrecht 2012
Abstract Peripheral artery disease (PAD) is a result of the atherosclerotic narrowing of blood vessels to the extremities, and the subsequent tissue ischemia can lead to the up-regulation of angiogenic growth factors and formation of new vessels as a recovery mechanism. Such formation of new vessels can be evaluated with various non-invasive molecular imaging techniques, where serial images from the same subjects can be obtained to allow the documentation of disease progression and therapeutic response. The most commonly used animal model for preclinical studies of PAD is the murine hindlimb ischemia model, and a number of radiotracers have been investigated for positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging of PAD. In this review article, we summarize the PET/SPECT tracers that have been tested in the murine hindlimb ischemia model as well as those used clinically to assess the extremity blood flow. Keywords Hindlimb ischemia Peripheral artery disease (PAD) Angiogenesis Positron emission tomography
H. Orbay H. Hong W. Cai (&) Department of Radiology, School of Medicine and Public Health, University of Wisconsin, Madison, 1111 Highland Ave, Room 7137, Madison, WI 53705-2275, USA e-mail: [email protected] Y. Zhang W. Cai Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin, Madison, 1111 Highland Ave, Room 7137, Madison, WI 53705-2275, USA W. Cai University of Wisconsin Carbone Cancer Center, Madison, WI, USA
(PET) Single photon emission computed tomography (SPECT) Molecular imaging
Introduction Peripheral arterial disease (PAD) is predominantly a disease of the elderly population and the incidence rate is increasing as the western world population continues to age. Prevalence of PAD in asymptomatic adults over 40 years old is 4.2 % in the United States, which can be as high as 7.0 % in those with metabolic syndrome [1]. PAD is a consequence of systemic atherosclerosis that leads to progressive narrowing of the arteries to many different organs, and the circulation of the lower extremities is the most frequently involved [1]. As a compensatory response to ischemia, the human body upregulates the expression of angiogenic growth factors, such as vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), hepatocyte growth factor (HGF), and the corresponding receptors that collectively can stimulate the development of collateral vessels [2]. In cases that these biological compensatory mechanisms fail (which usually do), therapeutic interventions such as exercise training, surgical bypass grafting, exogenous growth factors, gene/stem cell therapies, and drug delivery systems can be used to help the reconstitution of ext
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