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Molecular imaging is broadly defined as the visualization of molecular and cellular processes on either a macro- or microscopic level. Because of its high spatial resolution and ability to noninvasively visualize internal organs, magnetic resonance (MR) imaging is widely believed to be an ideal platform for ''in vivo'' molecular imaging.〔Rodriguez I, Perez-Rial S, Gonzalez-Jiminez J, et al., Magnetic Resonance Methods and Applications in Pharmaceutical Research. J Pharma Sci, 28 Jan. 2008 (E-publication ahead of print)〕 For this reason, MR contrast agents that can detect molecular events are an active field of research.〔Meade TJ, Taylor AK, and Bull SR, New magnetic resonance contrast agents as biochemical reporters. Curr Opin Neurobiol 13, pp. 597-602.〕 One group of compounds that has shown particular promise is enzyme-activated MR contrast agents. Enzyme-activated MR contrast agents are compounds that cause a detectable change in image intensity when in the presence of the active form of a certain enzyme. This makes them useful for ''in vivo'' assays of enzyme activity. They are distinguished from current, clinical MR contrast agents that give only anatomical information,〔Welssleder R, and Umar M, Molecular Imaging. Radiology 219, pp. 316-333.〕 such as aqueous gadolinium compounds, by their ability to make molecular processes visible. Enzyme-activated contrast agents are powerful tools for molecular imaging. To date, β-galactosidase-activated contrast agents have attracted the most attention in the literature, although there no theoretical reason that other enzymes could not be used to activate contrast agents. Also, mechanisms other than enzyme activation, such as Ca2+-dependent activation, can theoretically be used.〔 In general, enzyme-activated agents contain a paramagnetic metal ion which can affect the T1 or T2 relaxation times for nearby water molecules. However, the metal ions are unable to interact with the water until an enzyme-catalyzed reaction takes place. Steric hindrance or coordination with other ions prevents water from accessing the paramagnetic center prior to the enzymatic reaction.〔Urbanczyk-Pearson LM, Femia FJ, Smith J, et al., Mechanistic Investigation of β-Galactosidase-Activated MR Contrast Agents. Inorg Chem 48, pp. 56-68〕 == Structure of β-galatosidase-activated contrast agents == Two distinct β-galatosidase-activated contrast agents have been reported. Both consist of a Gd(III) ion complexed with a tetraazamacrocycle. At the N-10 position, a two-carbon chain links the gadolinium-tertaazamacrocycle complex to a molecule of galactose. The galactose is linked to the complex by a β-glycosidic bond at its C-1 position.〔 The two forms of the contrast agent differ only in the location of a single methyl group. The first class, known as the α-series, has a methyl group bound to the carbon that is α to the tetraazamacrocycle. The other class, called the β-series, has a methyl attached to the β carbon relative to the tetraazamacrocycle. The position of this methyl group is significant for the structure of the agent, and thus determines the mechanism by which the non-active compound shields the Gd(III) ion from interacting with water. The α-series adopts a conformation in which the sugar lies directly over the paramagnetic center, thus sterically prohibitting water from accessing the gadolinium. The β-series, on the other hand, blocks water from the gadolinium by coordinating with a carbonate ion. There is no evidence that the stereochemical orientation of the methyl-bearing carbon affects the either the enzyme-catalyzed cleavage or the ability of the sugar to exclude water from the gadolinium ion.〔 Studies have shown that the α-series is far more effective at blocking water from the paramagnetic center prior to cleavage.〔 The need to coordinate with a carbonate ion and the lower level of signal suppression inherent to the β-series make the α-series a better candidate for use in research and clinical medicine. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Enzyme-activated MR contrast agents」の詳細全文を読む スポンサード リンク
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