In vivo PET measurement of expression of dopamine D2 receptor gene injected into rat striatum

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As the basic study of gene therapy, we investigated whether the expression of dopamine DィイD22ィエD2 receptor (DィイD22ィエD2R) gene injected into the rat striatum was evaluated in vivo by positron emission tomography (PET). preliminarily we established that the striatal DィイD22ィエD2R was evaluated by PET with ィイD111ィエD1C-labeled DィイD22ィエD2R-specific ligands by using normal rats and a rat model for striatal neurodegenerative diseases induced by striatal injection of quinolinic acid. To overcome the spatial resolution of PET camera, a technique of PET-MRI registration on the rat brain was developed.PET measurement demonstrated that the uptake of three kinds of DィイD22ィエD2R-specific ligands, [ィイD111ィエD1C]raclopride, [ィイD111ィエD1C]nemonapride and [ィイD111ィエD1C]N-methylspiperone was higher in the striatum injected with the vectors for DィイD22ィエD2R than the contralateral striatum injected with a control vector 2-3 days after injection. The uptake of [ィイD111ィエD1C]SCH 23390, a dopamine DィイD21ィエD2 receptor … More specific ligand, or [ィイD111ィエD1C]β-CIT-FP, a dopamine transporter specific tracer, was not different between bilateral striata, and co-injection of excess unlabeled raclopride inhibited the uptake of [ィイD111ィエD1C]raclopride, suggesting the PET signal reflects the DィイD22ィエD2R-specific gene-expression. These findings were confirmed by ex vivo and in vitro autoradiography. At day 16 the increased uptake of [ィイD111ィエD1C]raclopride declined to basal level, suggesting that the gene expression is temporary.We concluded that PET imaging is capable of detecting adenovirus-mediated gene transfer in vivo. This technique represents a major advance over in vitro ARG analysis of DィイD22ィエD2R binding which must be done post-hoc. PET imaging permits in vivo analysis of the efficiency of DィイD22ィエD2R gene transfer that can be followed longitudinally and related to any functional changes being observed. Such imaging will prove highly valuable for assessment of gene transfer using this and similar vectors. Less