Purpose
We applied the in vivo measurement of pre- and post-synaptic dopaminergic function with Positron Emission Tomography (PET) to assess the alteration of neural transmission after fetal nigral transplantation to hemi-Parkinson model rats.
Method
We transplanted 4.0×10∧5 fetal mesencepharic cells in the damaged striatum of unilaterally 6-OHDA lesioned rats. We performed PET scans with [11C]PE2I (PET tracer of dopamine transporter) and [11C]raclopride (that of D2 receptor) to evaluate the pre- and post-synaptic dopaminergic function before, and 2 and 4 weeks after transplantation in the same individual. PET scan was performed in 2-dimensional acquisition mode with a high-resolution PET camera, SHR7700 (Hamamatsu Photonics). Rats were fixated by ear bar and incision bar under isoflurane anesthesia. After 20 min transmission scan for attenuation correction, 90 min dynamic emission scan started immediately after a tracer injection (ca. 37 MBq/ 300 ml) via tail-vein. The acquired images were reconstructed with a 4-mm of Hanning filter. The regions of interest were placed over the bilateral striatum and cerebellum. Regional binding potential (BP; k3/k4) of dopamine transporter and D2 receptor were calculated using a simplified reference tissue model, and cerebellum was used as reference region. Rotational behavior test with apomorphine and methamphetamine, in vitro autoradiography with [11C]PE2I and [11C]raclopride, and measurement of dopamine contents by HPLC were simultaneously performed.
Results
In the PET studies, binding potential of [11C]PE2I in the transplanted striatum increased significantly four weeks after the transplantation. Then the binding potential of [11C]raclopride, which was up-regulated in all experimental period in sham rats, decreased significantly 4 weeks after transplantations. In vitro autoradiographic studies corresponded with the results of PET studies. Number of rotations induced by methamphetamine and apomorphine injection significantly decreased after transplantation. Dopamine contents in the striatum significantly increased.
Discussion
The increase in the binding of [11C]PE2I in the transplanted striatum was detected with PET and it indicated not only survival, but maturation and function of the transplanted cells. Although the recovery of pre-synaptic function was incomplete, complete recovery of the rotational behavior test was observed 4 weeks after transplantation. These results strongly suggest the contribution of up-regulated post-synaptic D2 receptors to the recovery of the dopaminergic function. We considered that the serial and simultaneous PET measurement of pre- and post-synaptic dopaminergic function is inevitable to investigate the functional recovery of dopaminergic function by the neural transplantation therapy.