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: Shao-Ju Weng, Chyng-Yann Shiue, Wen-Sheng Huang, Cheng-Yi Cheng, San-Yuan Huang, I-Hsun Li, Chih-Chieh Tao, Ta-Kai Chou, Mei-Hsiu Liao, Yung-Ping Chang, Kuo-Hsing Ma
• Journal: Cell transplantation (Cell Transplant) Vol. 22 Issue 7 Pg. 1295-305 ( 2013) ISSN: 1555-3892 [Electronic] United States
• PMID: 23127756 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fluorine Radioisotopes
• Serotonin Plasma Membrane Transport Proteins
• Oxidopamine
• ADAM Proteins

Topics

• ADAM Proteins (chemistry, metabolism, pharmacology)
• Animals
• Brain (diagnostic imaging, drug effects)
• Disease Models, Animal
• Dopaminergic Neurons (physiology)
• Fluorine Radioisotopes (chemistry)
• Immunohistochemistry
• Male
• Mesencephalon (cytology, transplantation)
• Odds Ratio
• Oxidopamine (pharmacology)
• Parkinson Disease (diagnostic imaging, metabolism, pathology)
• Positron-Emission Tomography
• Rats
• Rats, Sprague-Dawley
• Serotonergic Neurons (physiology)
• Serotonin Plasma Membrane Transport Proteins (metabolism)
• Transplantation, Homologous