Real-time MR imaging of adeno-associated viral vector delivery to the primate brain.
We are developing a method for real-time magnetic resonance imaging (MRI) visualization of convection-enhanced delivery (CED) of adeno-associated viral vectors (AAV) to the primate brain. By including gadolinium-loaded liposomes (GDL) with AAV, we can track the convective movement of viral particles by continuous monitoring of distribution of surrogate GDL. In order to validate this approach, we infused two AAV (AAV1-GFP and AAV2-hAADC) into three different regions of non-human primate brain (corona radiata, putamen, and thalamus). The procedure was tolerated well by all three animals in the study. The distribution of GFP determined by immunohistochemistry in both brain regions correlated closely with distribution of GDL determined by MRI. Co-distribution was weaker with AAV2-hAADC, although in vivo PET scanning with FMT for AADC activity correlated well with immunohistochemistry of AADC. Although this is a relatively small study, it appears that AAV1 correlates better with MRI-monitored delivery than does AAV2. It seems likely that the difference in distribution may be due to differences in tissue specificity of the two serotypes.
Fiandaca
Massimo S
MS
Department of Neurological Surgery, University of California San Francisco, 1855 Folsom Street, Room 226, San Francisco, CA 94103, USA.
Varenika
Vanja
V
Eberling
Jamie
J
McKnight
Tracy
T
Bringas
John
J
Pivirotto
Phillip
P
Beyer
Janine
J
Hadaczek
Piotr
P
Bowers
William
W
Park
John
J
Federoff
Howard
H
Forsayeth
John
J
Bankiewicz
Krystof S
KS
D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000235:genetics / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging* / Q000502:physiology / Q000821:virology*; D000229:Dependovirus / Q000235:genetics*; D005682:Gadolinium; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008081:Liposomes; D008253:Macaca mulatta; D008279:Magnetic Resonance Imaging; D008297:Male; D049268:Positron-Emission Tomography; D011699:Putamen / Q000821:virology; D013788:Thalamus / Q000821:virology
D008081:Liposomes; D049452:Green Fluorescent Proteins; D005682:Gadolinium; D001142:Aromatic-L-Amino-Acid Decarboxylases