Apoptosis Imaging
Apoptosis, which was first proposed by Kerr in 1972, is a basic physiological mechanism of life, and it is also the pathological basis for the development of many diseases [1]. With the deepening of research, increasingly explicit about mechanism of apopt
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Hui Wang and Xiao-Jun Zhang
Apoptosis, which was first proposed by Kerr in 1972, is a basic physiological mechanism of life, and it is also the pathological basis for the development of many diseases [1]. With the deepening of research, increasingly explicit about mechanism of apoptosis was considered to be one of the most important progresses in biological field in recent decades. In the field of cancer treatment, apoptosis has a broad application prospect in the observation of curative effect or new drug evaluation. Radionuclide imaging using radiopharmaceuticals detects apoptosis by targeting apoptotic cells with high sensitivity and specificity. With decades of effort, the radioactive probes for different targets of the apoptotic cells were developed and evaluated. Many kinds of probes have been applied in clinical research [2].
14.1 B asic Physiology, Biology, and Pathophysiology of Apoptosis The physiological, biological, and pathophysiological characteristics of apoptosis differ substantially from other cell death patterns.
14.1.1 Definition of Apoptosis The term “apoptosis” contains two Greek roots “apo” and “ptosis,” which means “from” and “falling,” respectively. Apoptosis is known as programmed cell death that participates in cell growth, differentiation, the immune system regulation, and clearing abnormal cells [3]. Dysregulated apoptotic progress would result in harmful effects on normal tissues in various conditions, including tumor development H. Wang (*) Nuclear Medicine Department, Hainan Branch of the Chinese PLA General Hospital, Sanya, P. R. China X.-J. Zhang Nuclear Medicine Department, The Chinese PLA General Hospital, Beijing, P. R. China
that is due to too little apoptosis or neurodegenerative diseases and autoimmune disorder because of too much apoptosis [4].
14.1.2 Molecular Biological Mechanism The mechanism of cell apoptosis is precise and complex, which belongs to the cascade reaction of energy-consuming molecules. The apoptotic process is mainly induced by two well-defined cellular pathways, the intrinsic pathway and the extrinsic pathway. Infection, radiation, heat, nutrient deprivation, glucocorticoids, or exorbitant intracellular calcium concentration can cause the release of apoptotic signals in cells, and extracellular signals were usually induced by toxic nitric oxide. Two distinct but convergent pathways can initiate apoptotic receptor pathways. Both apoptotic pathways shared a common cascade named caspases, consisting of cysteine-dependent aspartate-specific proteases. Executioner caspases degrade intercellular components in order to induce the morphological changes for apoptosis, finally disposed by macrophages. This program protects the microenvironment from proteolytic enzymes and cytosolic material during apoptosis. Multiple inducements of apoptosis are known, including growth factor withdrawal, chemotherapy, DNA damage, immunoreaction, and ischemic injury. The interval between the trigger of apoptosis and the time of detectable biologic reactions largely depen
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