In vivo assessment of adenoviral vector-mediated gene expression of dopamine D(2) receptors in the rat striatum by positron emission tomography.
For functional assessment of gene therapy in experimental animals, in vivo assessment of transferred genes will provide a major advance over an in vitro analysis which must be done post-hoc. In the current study we conducted positron emission tomography (PET) analysis in rats following injection of the adenoviral vector encoding the cDNA for the rat dopamine D(2) receptors (D(2)R) (AdCMV.DopD(2)R) into rat brain to provide a quantitative evaluation of D(2)R overexpression. Quantitative measurements as well as images by PET and ex vivo autoradiography demonstrated the significant increase of D(2)R binding of [(11)C]raclopride, a specific D(2)R radioligand, in the AdCMV.DopD(2)R-injected rat striatum 2 or 3 days after vector injection. Longitudinal in vivo assessment of the gene expression by PET demonstrated decreased binding of [(11)C]raclopride with time, which was in agreement with the observation in a cross-sectional autoradiographic study. The results of the current study demonstrate that PET can be used for longitudinal in vivo assessment of D(2)R expression mediated by adenoviral vector in rat brain.
Umegaki
Hiroyuki
H
Department of Geriatrics, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, Aichi 466-8550 Japan. umegaki@tsuru.med.nagoya-u.ac.jp
Ishiwata
Kiichi
K
Ogawa
Osamu
O
Ingram
Donald K
DK
Roth
George S
GS
Yoshimura
Juri
J
Oda
Keiichi
K
Matsui-Hirai
Hisako
H
Ikari
Hiroyuki
H
Iguchi
Akihisa
A
Senda
Michio
M
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology*; D003342:Corpus Striatum / Q000000981:diagnostic imaging* / Q000187:drug effects; D018492:Dopamine Antagonists; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D015316:Genetic Therapy / Q000295:instrumentation / Q000379:methods; D005822:Genetic Vectors; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D020891:Raclopride; D051381:Rats; D011916:Rats, Inbred F344; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D014055:Tomography, Emission-Computed
D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D020891:Raclopride