A bacterial gene, mms6, as a new reporter gene for magnetic resonance imaging of mammalian cells.

Abstract

Magnetic resonance imaging (MRI) allows for noninvasive, deep tissue imaging with high spatial resolution, making it an attractive modality for in vivo cellular imaging. Since reporter genes can generate magnetic resonance (MR) contrast based on molecular activity, they offer a potentially powerful tool for cellular imaging. The mms6 gene was originally identified in magnetotactic bacteria (MTB), which is known to play a key role in magnetic crystal formation. The purpose of the present work was to investigate the possibility of using mms6 as an MR reporter gene. We established a transgenic mammalian cell line that stably expresses mms6. In vitro experiments show that mms6-expressing cells form clusters of nanoparticles within and outside membrane-enclosed structures and produce changes in MR contrast, most likely by increasing iron uptake of intracellular iron. Additionally, in vivo MRI experiments demonstrate that mms6-expressing tumors can be distinguished from parental tumors not expressing mms6, even in the absence of exogenous iron supplementation. Our results demonstrate that mms6 can function as an MR reporter gene with the potential to monitor gene expression and to visualize the proliferation, migration, and metastasis of tumor cells expressing it.