title: PET imaging of serotonin transporters with 4-[18F]-ADAM in a Parkinsonian rat model.
abstract: This study was undertaken to address the effects of fetal mesencephalic tissue transplantation on the serotonin system in a rat model of Parkinson's disease (PD) while also investigating the usefulness of 4-[18F]-ADAM (a serotonin transporter imaging agent) coupled with micro-PET for imaging serotonin transporters (SERTs). A PD model was induced by unilateral injection of 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle of the nigrostriatal pathway, while cell transplantation was performed via intrastriatal injection of mesencephalic brain tissue dissected from embryonic (E14) rats. The 4-[18F]-ADAM/micro-PET scanning was performed following both 6-OHDA lesioning and transplantation. Immunohistochemistry (IHC) studies were also performed following the final PET scan, and the results were compared to show a 17-43% decrease in the specific uptake ratio (SUR) and a 23-52% decrease in serotonin transporter immunoreactivity (SERT-ir) within various brain regions on the lesioned side. The number of methamphetamine-induced rotations also decreased significantly at the 4th week postgraft. In addition, striatal SUR and the SERT-ir levels were restored to 77% and 83% 5 weeks postgraft. These results suggest that Parkinson's disease also affects the serotonergic system, while both the dopaminergic and serotonergic systems can be partially restored in a rat model of PD after E14 mesencephalic tissue transplantation. In addition, we have also determined that 4-[18F]-ADAM/micro-PET can be used to detect serotonergic neuron loss, monitor the progress of Parkinson's disease, and oversee the effectiveness of therapy.
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Shao-Ju
authors.initials: SJ
authors.lastname: Weng
authors.forename: Chyng-Yann
authors.initials: CY
authors.lastname: Shiue
authors.forename: Wen-Sheng
authors.initials: WS
authors.lastname: Huang
authors.forename: Cheng-Yi
authors.initials: CY
authors.lastname: Cheng
authors.forename: San-Yuan
authors.initials: SY
authors.lastname: Huang
authors.forename: I-Hsun
authors.initials: IH
authors.lastname: Li
authors.forename: Chih-Chieh
authors.initials: CC
authors.lastname: Tao
authors.forename: Ta-Kai
authors.initials: TK
authors.lastname: Chou
authors.forename: Mei-Hsiu
authors.initials: MH
authors.lastname: Liao
authors.forename: Yung-Ping
authors.initials: YP
authors.lastname: Chang
authors.forename: Kuo-Hsing
authors.initials: KH
authors.lastname: Ma
mesh_terms: D051722:ADAM Proteins / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000502:physiology; D005462:Fluorine Radioisotopes / Q000737:chemistry; D007150:Immunohistochemistry; D008297:Male; D008636:Mesencephalon / Q000166:cytology / Q000637:transplantation; D016017:Odds Ratio; D016627:Oxidopamine / Q000494:pharmacology; D010300:Parkinson Disease / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D049268:Positron-Emission Tomography; D051381:Rats; D017207:Rats, Sprague-Dawley; D059326:Serotonergic Neurons / Q000502:physiology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D014184:Transplantation, Homologous
chemical_list: D005462:Fluorine Radioisotopes; D050486:Serotonin Plasma Membrane Transport Proteins; D016627:Oxidopamine; D051722:ADAM Proteins