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In Vivo PET Measurements With [11C]PE2I to Evaluate Fetal Mesencephalic Transplantations to Unilateral 6-OHDA-Lesioned Rats

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Abstract:

Positron emission tomography (PET) is a useful tool to assess and visualize neurotransmissions in vivo. In this study, we performed repeated PET scans with [11C]PE2I, a tracer of the dopamine transporter, to evaluate the alteration of the expression of dopamine (DA) transmission component after a fetal mesencephalic transplantation. The fetal mesencephalic cells were transplanted into the striatum of unilateral 6-OHDA-lesioned rats. PET scans with [11C]PE2I were performed to evaluate the DA transporter before and 2 and 4 weeks after the transplantation. Rotation behavior tests, in vitro autoradiography, measurements of DA contents in the striatum by high-performance liquid chromatography (HPLC), and tyrosine hydroxylase (TH) immunohistological examinations were performed at the same time points and examined for their relationship to changes in the dopamine transporter. The number of ipsilateral rotations induced by methamphetamine injections decreased. DA contents in the striatum measured with HPLC significantly increased. In the PET study, the binding potential of [11C]PE2I increased at 4 weeks. The results of the in vitro autoradiography study corresponded with those of the PET study. The degrees of the change in the binding potentials correlated with those of the numbers of rotations in the behavioral study and the DA contents in the striatum. In the histological examination, TH-positive cells with axons were observed at 2 and 4 weeks after the transplantation. As the dopamine transporter exists only in the axon terminal of DA neurons, these results suggested that PET measurements of [11C]PE2I binding indicated not only survival, but maturity and functioning of the transplanted cells. Repeated PET measurements of DA transporters are a useful tool in assessing the effectiveness of neural transplantations.

Keywords: 6-Hydroxydopamine (6-OHDA); Dopamine transporter; PE2I; PET; Transplantation

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/000000005783982684

Affiliations: 1: Brain Imaging Project, National Institute of Radiological Science, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan, Department of Neurosurgery, Tokyo Medical and Dental University, Tokyo 113-8519, Japan 2: Department of Physiology, Keio University School of Medicine, Tokyo 160-8582, Japan, Japanese Scientific and Technology Agency, Core Research for Evolutional Science and Technology (CREST), Tokyo, Japan 3: Brain Imaging Project, National Institute of Radiological Science, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan 4: Department of Neurosurgery, Tokyo Medical and Dental University, Tokyo 113-8519, Japan 5: Neurobehavioral Unit, Central Institute for Experimental Animal, Kawasaki 216-0001, Japan

Publication date: September 1, 2005

More about this publication?
  • Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.
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