Analytical Sciences

In vivo Imaging of Brain Dopaminergic Neurotransmission System in Small Animals with High-resolution Single Photon Emission Computed Tomography

Hideo SAJI,*  Yasuhiko IIDA,** Hidekazu KAWASHIMA,* Mikako OGAWA,* Youji KITAMURA,* Takahiro MUKAI,* Seiichiro SHIMAZU,** and Fumiro YONEDA**

*Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan
**Fujimoto Pharmaceutical Corporation, Nishiotsuka, Matsubara 580-0011, Japan

High-resolution single photon emission computed tomography (SPECT) provides a unique capability to image the biodistribution of radiolabeled molecules in small laboratory animals. Thus, we applied the high-resolution SPECT to in vivo imaging of the brain dopaminergic neurotransmission system in common marmosets using two radiolabeled ligands, [¹²³I]2beta-carbomethoxy-3beta-(4-iodophenyl)tropane (beta-CIT) as a dopamine transporter (DAT) ligand and [¹²³I]iodobenzamide (IBZM) as a dopamine D₂ receptor (D₂R) ligand. Specific images of the striatum, a region with a high density of dopaminergic synapses, were obtained at 240 min and 60 min after injection of [¹²³I] beta-CIT and [¹²³I]IBZM, respectively. Furthermore, a significantly low accumulation of [¹²³I]beta-CIT in the striatum was observed in MPTP-treated animals compared with results for a control group, and a similar accumulation in the control group was observed with the pretreatment of deprenyl in the MPTP-treated animals. However, the striatal accumulation of [¹²³I]IBZM showed no changes among the control, MPTP-treated, and deprenyl-MPTP-treated groups. These SPECT imaging results agreed well with those of DA concentration and motor behavior. Since MPTP destroys nigrostriatal dopamine nerves and produces irreversible neurodegeneration associated with Parkinsonian syndrome, SPECT imaging data in this study demonstrated that deprenyl shows its neuroprotective effect on Parkinsonism by protecting against the destruction of presynaptic dopamine neurons.

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