MR imaging of gene transcription is important as it should enable the non-invasive detection of
mRNA alterations in disease. A range of MRI methods have been proposed for in vivo molecular imaging of cells based on the use of ultra-small super-paramagnetic
iron oxide (
USPIO) nanoparticles and related susceptibility weighted imaging methods. Although immunohistochemistry can robustly differentiate the expression of
protein variants, there is currently no direct gene assay technique that is capable of differentiating established to differentiate the induction profiles of c-Fos
mRNA in vivo. To visualize the differential FosB gene expression profile in vivo after
burn trauma, we developed MR probes that link the T2*
contrast agent [superparamagnetic iron oxide nanoparticles (SPION)] with an
oligodeoxynucleotide (ODN) sequence complementary to FosB
mRNA to visualize endogenous
mRNA targets via in vivo hybridization. The presence of this SPION-ODN probe in cells results in localized signal reduction in T2*-weighted MR images, in which the rate of signal reduction (R2*) reflects the regional
iron concentration at different stages of
amphetamine (AMPH) exposure in living mouse tissue. Our aim was to produce a superior
contrast agent that can be administered using systemic as opposed to local administration and which will target and accumulate at sites of
burn injury. Specifically, we developed and evaluated a PEGylated
lipid coated MR probe with ultra-small super-paramagnetic iron oxide nanoparticles (USPION, a T2 susceptibility agent) coated with cationic fusogenic
lipids, used for cell transfection and gene delivery and covalently linked to a phosphorothioate modified
oligodeoxynucleotide (sODN) complementary to c-Fos
mRNA (SPION-cFos) and used the agent to image mice with leg
burns. Our study demonstrated the feasibility of monitoring
burn injury using MR imaging of c-Fos transcription in vivo, in a clinically relevant mouse model of
burn injury for the first time.