1. ¹Department of Biotechnology and Molecular Medicine, University of Kuopio, Kuopio, Finland
2. ²Ark Therapeutics Oy, Neulaniementie 2L9, Kuopio, Finland
3. ³Cellular and Molecular Imaging Group, Department of Biomedical NMR, AI Virtanen Institute for Molecular Sciences, Kuopio, Finland
4. ⁴Department of Biological and Environmental Science, University of Jyväskylä, Jyväskylä, Finland
5. ⁵Department of Chemistry, University of Kuopio, Kuopio, Finland
6. ⁶Department of Medicine and Gene Therapy Unit, University of Kuopio, Kuopio, Finland
7. ⁷Department of Clinical Radiology, University of Kuopio, Kuopio, Finland

Correspondence: JK Räty, Department of Biotechnology and Molecular Medicine, University of Kuopio, PO Box 1627, FIN 70211 Kuopio, Finland. E-mail: jani.raty@uku.fi (JK Räty);; J Hakumäki or S Ylä-Herttuala, AI Virtanen Institute for Molecular Sciences, University of Kuopio, PO Box 1627, FZN-70211, Kuopio, Finland. E-mails: Juhana.Hakumaki@uku.fi (JM Hakumäki); Seppo.Ylaherttuala@uku.fi (S Ylä-Herttuala)

⁸These authors contributed equally to the work

Received 1 March 2006; Revised 12 June 2006; Accepted 13 June 2006; Published online 20 July 2006.

Abstract

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 10¹⁰ 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 -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.