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Am J Nucl Med Mol Imaging 2012;2(4):432-447
Review Article
Radiolabelled probes for imaging of atherosclerotic plaques
Takashi Temma, Hideo Saji
Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, 46- 29 Yoshida
Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Received June 5, 2012; Accepted July 20, 2012; Epub October 15, 2012; Published October 30, 2012
Abstract: Cardiovascular disease is the leading cause of death worldwide. Unstable atherosclerotic plaques are prone to rupture
followed by thrombus formation, vessel stenosis, and occlusion and frequently lead to acute myocardial infarction and brain
infarction. As such, unstable plaques represent an important diagnostic target in clinical settings and the specific diagnosis of
unstable plaques would enable preventive treatments for cardiovascular disease. To date, various imaging methods such as
computed tomography (CT), magnetic resonance imaging (MRI), ultrasound (US), and intravascular ultrasound (IVUS) have been
widely used clinically. Although these methods have advantages in terms of spatial resolution and the ability to make detailed
identification of morphological alterations such as calcifications and vessel stenosis, these techniques require skill or expertise to
discriminate plaque instability, which is essential for early diagnosis and treatment and can present difficulties for quantitative
estimation. On the other hand, nuclear imaging techniques such as positron emission tomography (PET) and single photon
emission computed tomography (SPECT) can noninvasively collect quantitative information on the expression levels of functional
molecules and metabolic activities in vivo and thus provide functional diagnoses of unstable plaques with high sensitivity.
Specifically, unstable plaques are characterized by an abundance of invasive inflammatory cells (macrophages), increased oxidative
stress that increases oxidized LDL and its receptor expressed on cells in the lesions, increased occurrence of apoptosis of
macrophages and other cells involved in disease progression, increased protease expression and activity, and finally thrombus
formation triggered by plaque rupture, which is the most important mechanism leading to the onset of infarctions and ischemic
sudden death. Therefore, these characteristics can all be targets for molecular imaging by PET and SPECT. In this paper, we review
the present state and future of radiolabelled probes that have been developed for detecting atherosclerotic unstable plaques with
nuclear imaging techniques. (ajnmmi1206002).
Keywords: Molecular imaging, atherosclerosis, plaque, positron emission tomography, single photon emission computed
tomography, 2-[18F]Fluoro-2-deoxy-D-glucose, lectin-like oxidized low density lipoprotein receptor-1, apoptosis, matrix
metalloproteinase, thrombus
Address all correspondence to:
Dr. Hideo Saji
Department of Patho-Functional Bioanalysis
Graduate School of Pharmaceutical Sciences
Kyoto University, 46-29 Yoshida Shimoadachi-cho
Sakyoku, Kyoto 606-8501, Japan.
Tel: +81-75-753-4556; Fax: +81-75-753-4568
E-mail: hsaji@pharm.kyotou.ac.jp
Review Article
Radiolabelled probes for imaging of atherosclerotic plaques
Takashi Temma, Hideo Saji
Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, 46- 29 Yoshida
Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Received June 5, 2012; Accepted July 20, 2012; Epub October 15, 2012; Published October 30, 2012
Abstract: Cardiovascular disease is the leading cause of death worldwide. Unstable atherosclerotic plaques are prone to rupture
followed by thrombus formation, vessel stenosis, and occlusion and frequently lead to acute myocardial infarction and brain
infarction. As such, unstable plaques represent an important diagnostic target in clinical settings and the specific diagnosis of
unstable plaques would enable preventive treatments for cardiovascular disease. To date, various imaging methods such as
computed tomography (CT), magnetic resonance imaging (MRI), ultrasound (US), and intravascular ultrasound (IVUS) have been
widely used clinically. Although these methods have advantages in terms of spatial resolution and the ability to make detailed
identification of morphological alterations such as calcifications and vessel stenosis, these techniques require skill or expertise to
discriminate plaque instability, which is essential for early diagnosis and treatment and can present difficulties for quantitative
estimation. On the other hand, nuclear imaging techniques such as positron emission tomography (PET) and single photon
emission computed tomography (SPECT) can noninvasively collect quantitative information on the expression levels of functional
molecules and metabolic activities in vivo and thus provide functional diagnoses of unstable plaques with high sensitivity.
Specifically, unstable plaques are characterized by an abundance of invasive inflammatory cells (macrophages), increased oxidative
stress that increases oxidized LDL and its receptor expressed on cells in the lesions, increased occurrence of apoptosis of
macrophages and other cells involved in disease progression, increased protease expression and activity, and finally thrombus
formation triggered by plaque rupture, which is the most important mechanism leading to the onset of infarctions and ischemic
sudden death. Therefore, these characteristics can all be targets for molecular imaging by PET and SPECT. In this paper, we review
the present state and future of radiolabelled probes that have been developed for detecting atherosclerotic unstable plaques with
nuclear imaging techniques. (ajnmmi1206002).
Keywords: Molecular imaging, atherosclerosis, plaque, positron emission tomography, single photon emission computed
tomography, 2-[18F]Fluoro-2-deoxy-D-glucose, lectin-like oxidized low density lipoprotein receptor-1, apoptosis, matrix
metalloproteinase, thrombus
Address all correspondence to:
Dr. Hideo Saji
Department of Patho-Functional Bioanalysis
Graduate School of Pharmaceutical Sciences
Kyoto University, 46-29 Yoshida Shimoadachi-cho
Sakyoku, Kyoto 606-8501, Japan.
Tel: +81-75-753-4556; Fax: +81-75-753-4568
E-mail: hsaji@pharm.kyotou.ac.jp
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