Magnetic resonance imaging of viral particle biodistribution in vivo.
We describe here a technique for the visualization of viral vector delivery by magnetic resonance imaging (MRI) in vivo. By conjugating avidin-coated baculoviral vectors (Baavi) with biotinylated ultra-small superparamagnetic iron oxide particles (USPIO), we are able to produce vector-related MRI contrast in the choroid plexus cells of rat brain in vivo over a period of 14 days. Ten microlitres of 2.5 x 10(10) PFU/ml nuclear-targeted LacZ-encoding Baavi with bUSPIO coating was injected into rat brain ventricles and visualized by MRI at 4.7 T. As baculoviruses exhibit restricted cell-type specificity in the rat brain, altered MRI contrast was detected in the choroid plexus of the injected ventricles. No specific signal loss was detected when wild-type baculoviruses or intact biotinylated USPIO particles were injected into the lateral ventricles. Cryosectioned brains were stained for nuclear-targeted beta-galactosidase gene expression, which was found to colocalize with MRI contrast. This study provides the first proof of principle for robust and non-invasive viral vector MRI by using avidin-displaying viruses in vivo. Considering the widespread use of MRI in current medical imaging, the approach is likely to provide numerous future applications in imaging of therapeutic gene transfer.
Räty
J K
JK
Department of Biotechnology and Molecular Medicine, University of Kuopio, Kuopio, Finland. jani.raty@uku.fi
Liimatainen
T
T
Wirth
T
T
Airenne
K J
KJ
Ihalainen
T O
TO
Huhtala
T
T
Hamerlynck
E
E
Vihinen-Ranta
M
M
Närvänen
A
A
Ylä-Herttuala
S
S
Hakumäki
J M
JM
D000818:Animals; D016367:Baculoviridae / Q000235:genetics / Q000648:ultrastructure*; D015415:Biomarkers; D001921:Brain / Q000821:virology*; D005290:Ferric Compounds; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage; D008279:Magnetic Resonance Imaging; D053758:Nanoparticles; D051381:Rats; D014018:Tissue Distribution; D014161:Transduction, Genetic; D001616:beta-Galactosidase / Q000235:genetics
D015415:Biomarkers; D005290:Ferric Compounds; C000499:ferric oxide; D001616:beta-Galactosidase