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Magnetic Resonance: It’s a Gas!

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Science Translational Medicine  07 May 2014:
Vol. 6, Issue 235, pp. 235ec80
DOI: 10.1126/scitranslmed.3009302

What happens when bacteria have gas? A new report by Shapiro et al. suggests that gas vesicles produced naturally by bacteria can be used to encapsulate hyperpolarized agents for magnetic resonance imaging (MRI). The resulting vesicles not only provide a stable environment for agents such as the noble gas xenon, but have a much brighter MR signal than that of conventional hydrogen (1H), the authors report.

Protein-coated gas-filled vesicles (GVs) are genetically encoded by prokaryotes and are used to regulate their buoyancy when in search of light or nutrients. The authors found that these protein vesicles could bind a highly polarized version of xenon from the surrounding solution, creating a strong MR signal in the cell. As the 129Xe moved in and out of the GVs, in rapid exchange with surrounding solution, the researchers could measure the chemical shift in a technique known as HyperCEST (chemical exchange through saturation transfer). Measuring 129Xe with HyperCESTdemonstrated sensitivity down to the mid-picomolar range, which was better than other genetically encoded MRI reporters, including green fluorescent protein. Furthermore, GVs from different organisms produced distinct shifts and could therefore be distinguished from one another, suggesting the ability to multiplex (measure many reporters at once).

These GV-based reporters could be used to track stem cells, watch cancers metastasize, and monitor molecular signaling in high-resolution whole-animal scans. To this end, Shapiro et al. took bacterially derived GVs and labeled them with antibodies against HER2. The functionalized GVs were then able to bind and signal the presence of HER2+ breast cancer cells in a heterogeneous culture in vitro. The next challenge is to translate these gassy genetic reporters to live animals for real-time imaging in vivo; the authors preliminarily examined the pharmacokinetics of these vesicles and believe that they could be used to image the brain and other highly vascularized organs.

M. G. Shapiro et al., Genetically encoded reporters for hyperpolarized xenon magnetic resonance imaging. Nat. Chem. 10.1038/nchem.1934 (2014). [Abstract]

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