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J Cereb Blood Flow Metab. 2009 Feb;29(2):434-40. doi: 10.1038/jcbfm.2008.137. Epub 2008 Nov 12.

Potential usefulness of D2R reporter gene imaging by IBF as gene therapy monitoring for cerebellar neurodegenerative diseases.

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Division of Tracer Kinetics, Advanced Science Research Center, Kanazawa University, Kanazawa, Ishikawa, Japan.


We investigated a gene expression imaging method to examine the level of therapeutic gene expression in the cerebellum. Using a human immunodeficiency virus derived lentivial vector, we expressed the dopamine D(2) receptor (D(2)R) as a reporter protein to mouse cerebellar Purkinje cells. Biodistribution and ex vivo autoradiography studies were performed by giving [(125)I]5-iodo-7-N-[(1-ethyl-2-pyrrolidinyl)methyl]carboxamide-2,3-dihydrobenzofuran ([(125)I]IBF) (1.85 MBq), as a radioactive D(2)R ligand, to model mice expressing the D(2)R with an HA tag (HA-D(2)R) in the cerebellum. In this study, [(125)I]IBF was bound to the D(2)R expressed in the cerebellum of the model mice selectively. Immunostaining was performed to confirm the HA-D(2)R expression in the cerebellum of the model mice. A significant correlation (r=0.900, P<0.001) between areas that expressed HA-D(2)R by immunostaining and areas in which [(125)I]IBF accumulated by the ex vivo autoradiograms was found. These results indicated that radioiodinated IBF is useful as a reporter probe to detect D(2)R reporter gene expression, which can be used for monitoring therapeutic gene expression in the cerebellum.

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