There is strong interest in MR imaging methods for in vivo MR imaging of gene transcription. Such imaging would enable MR detection of mRNA alterations in disease. A range of MRI methods bave 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 a gene assay technique is established to differentiate the induction profiles fosB and fosB mRNA in vivo, a superior contrast agent that will be administered using systemic as opposed to local administration and assess whether it will target and accumulate at the burn site is not available. To visualize in live tissue the differential fosB gene expression profile after burn trauma, we developed MR probes that link T2* contrast agent [superparamagnetic iron oxide nanoparticles (SPION)] with a oligodeoxynucleotide (ODN) sequence complementary to fosB or fosB mRNA to visualize endogenous mRNA targets via in vivo hybridization. The presence of this SPION-sODN 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 live mouse tissue. Following the successful transfection of the animals the mRNA expression is imaged and quantified in vivo. Specifically, we developed and delivered pegylated lipid coated MR probe with ultra-small super-paramagnetic iron oxide nanoparticles (USPION, a T2 susceptibility agent) coated with polymer modified fusogenic lipids and covalently linked to a phosphorothioate-modified oligodeoxynucleotide (sODN) complementary to c-fos mRNA (SPION-cfos) and imaged mice subjected leg burn. Our study demonstrates the feasibility to monitor burn injury using MR imaging of c-fosB? transcription in vivo, in a clinically relevant mouse model of burn trauma for the first time.
V. Righi, A. Papagiannaros, J. He, G. Dai, L. Rahme, V. Tugnoli, et al. (2011). Magnetic resonance imaging of c-fos gene transcription after burn trauma using a superior contrast agent.. NY : Curren Associates, Inc.
Magnetic resonance imaging of c-fos gene transcription after burn trauma using a superior contrast agent.
RIGHI, VALERIA;TUGNOLI, VITALIANO;
2011
Abstract
There is strong interest in MR imaging methods for in vivo MR imaging of gene transcription. Such imaging would enable MR detection of mRNA alterations in disease. A range of MRI methods bave 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 a gene assay technique is established to differentiate the induction profiles fosB and fosB mRNA in vivo, a superior contrast agent that will be administered using systemic as opposed to local administration and assess whether it will target and accumulate at the burn site is not available. To visualize in live tissue the differential fosB gene expression profile after burn trauma, we developed MR probes that link T2* contrast agent [superparamagnetic iron oxide nanoparticles (SPION)] with a oligodeoxynucleotide (ODN) sequence complementary to fosB or fosB mRNA to visualize endogenous mRNA targets via in vivo hybridization. The presence of this SPION-sODN 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 live mouse tissue. Following the successful transfection of the animals the mRNA expression is imaged and quantified in vivo. Specifically, we developed and delivered pegylated lipid coated MR probe with ultra-small super-paramagnetic iron oxide nanoparticles (USPION, a T2 susceptibility agent) coated with polymer modified fusogenic lipids and covalently linked to a phosphorothioate-modified oligodeoxynucleotide (sODN) complementary to c-fos mRNA (SPION-cfos) and imaged mice subjected leg burn. Our study demonstrates the feasibility to monitor burn injury using MR imaging of c-fosB? transcription in vivo, in a clinically relevant mouse model of burn trauma for the first time.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
