Molecular Imaging

Abstract

Molecular imaging is defined as the non-invasive visualization and measurement of biological processes at the molecular and cellular levels within living systems including humans.1Probes emitting signals, such as radiation, bioluminescence, fluorescence, and nuclear magnetic resonance, are often used to visualize in vivo molecular processes, such as gene expression and protein-protein interactions. The signals acquired through the probes are converted into images. Among the various signals, radiation is said to be highly sensitive and quantitative owing to its deep penetration into the body. Therefore, molecular imaging techniques using radiation, called nuclear medical molecular imaging, have been applied in various fields, including clinical diagnoses and preclinical studies of diseases, such as cancer2,3and Alzhermer’s disease.4,5Compared to nuclear medical molecular imaging, optical imaging using signals, such as bioluminescence and fluorescence, has a lower ability to penetrate into human tissues, which renders them unsuitable for whole-body diagnoses in clinical settings. However, the advantages of optical imaging are high spatiotemporal resolution, especially at cellular levels, and are cost-effective. Moreover, such optical imaging can involve high signal-to-background noise ratios when used with so-called “activatable” probes, where the fluorescent signals are turned on only after they interact with the target molecules. Wu et al. developed an activatable probe (MW-PD) to detect palladium. MW-PD showed high selectivity and sensitivity for palladium and had a detection limit of 8.0 nM. Fluorescence imaging of palladium-treated living cells was also successfully performed.6Wang et al. developed an innovative BODIPY- based fluorescent probe (BDP-DM) for detecting cysteine (Cys). BDP-DM reacted only with Cys, and not with other intracellular biothiols, such as homocysteine (Hcy) and glutathione (GSH). Intracellular Cys could be detected by fluorescent imaging with BDP-DM.7Other research groups have also attempted to distinguish intracellular biothiols using different probes. Men et al. developed a cyanine-based near-infrared fluorescent probe (Cy-S-Py) that could sense Cys and Hcy (but not GSH) at a detection limit of 0.17 μM. This probe could be used for cellular and in vivo imaging. It enabled the visualization of Cys/Hcy in HeLa cells and mice.8Zhu et al. developed a fluorescent probe (NR-NBD) by conjugating Nile red dye and 4-chloro-7-nitro-1,2,3-benzoxadiazole. This probe had a unique characteristic: both green (548 nm) and red (652 nm) fluorescence emissions were observed upon reacting with Cys/ Hcy, while only red fluorescence emission was observed upon reacting with GSH. NR-NBD efficiently discriminates Cys/Hcy from GSH, both in vitro (living cells) and in vivo (zebrafish).9Magnetic resonance imaging (MRI) also needs to be mentioned because it has been widely used for clinical diagnosis. The advantages of MRI are its extremely high spatial resolution and having no radiation exposure. Hyperpolarized MRI has recently attracted much attention because it is expected to overcome the problem of low sensitivity. Fujiwara et al. successfully developed a novel system for 129Xe hyperpolarized MRI.10Molecular imaging is a useful method for visualizing physiological functions and disease-related changes at molecular levels in vivo. In addition to the aforementioned information, the following references would be helpful for an in-depth understanding of the recent promising advances concerning molecular imaging in various fields of research.11–13