The MRI contrast agent gadoteridol enhances distribution of rAAV1 in the rat hippocampus

• Published in: Gene therapy Vol. 20; no. 12; pp. 1172 - 1177
• Main Authors: Hullinger, R, Ugalde, J, Purón-Sierra, L, Osting, S, Burger, C
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.12.2013; Nature Publishing Group
• Subjects: 631/326/596/2561; 631/378/1595/1554; 631/61/2300; Adeno-associated virus; Adenoviruses; Animals; Biomedical and Life Sciences; Biomedicine; Brain; Cell Biology; Contrast agents; Contrast media; Dependovirus - genetics; Dependovirus - physiology; Dependoviruses; Gadolinium - pharmacology; Gene Expression; Gene Therapy; Genetic Vectors; Green Fluorescent Proteins - genetics; Heterocyclic Compounds - pharmacology; Hippocampus; Hippocampus - virology; Human Genetics; Magnetic resonance imaging; Methods; Nanotechnology; Neostriatum; Neuroimaging; Neurological disorders; NMR; Nuclear magnetic resonance; Organometallic Compounds - pharmacology; original-article; Physiological aspects; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Rodents; Spatial memory; Testing; Transduction; Transduction, Genetic; Viral Tropism; hippocampus; gadoteridol; AAV; spatial memory
• ISSN: 0969-7128; 1476-5462
• DOI: 10.1038/gt.2013.47

Contrast agents are commonly used in combination with magnetic resonance imaging (MRI) to monitor the distribution of molecules in the brain. Recent experiments conducted in our laboratory have shown that co-infusion of recombinant Adeno-associated virus serotype 5 (rAAV5) and the MRI contrast agent gadoteridol (Gd) enhances vector transduction in the rat striatum. The goal of this study was to determine whether gadoteridol may also be used as a tool to enhance transduction efficiency of rAAV1 and rAAV5 within the rat hippocampus. We show that Gd/rAAV1-GFP but not Gd/rAAV5-GFP co-infusion results in significantly higher distribution of the transgene both in the injected hemisphere as well as in the contralateral side and adjacent areas of cortex along the injection track. We also show that Gd/rAAV1-GFP co-infusion has no deleterious effect on hippocampal function as assessed by two tests of spatial memory formation. This work indicates that Gd can be exploited as a method to increase transduction efficiency of AAV1 in the hippocampus for animal studies.