1999 Fiscal Year Final Research Report Summary
Development of optically active radioligand for biomedical imaging of neurotrasmission
| Project/Area Number |
10470474
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Physical pharmacy
|
|---|
| Research Institution | KYOTO UNIVERSITY |
|---|
Principal Investigator |
SAJI Hideo Kyoto University, Graduate School of Pharmaceutical Sciences, Professor, 薬学研究科, 教授 (40115853)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
OHMOMO Yoshiro Osaka University of Pharmaceutical Sciences, Associate Professor, 助教授 (70183241)
MAGATA Yasuhiro Kyoto University, Graduate School of Pharmaceutical Sciences, Associate Professor, 薬学研究科, 助教授 (20209399)
|
|---|
| Project Period (FY) |
1998 – 1999
|
| Keywords | Brain / Nicotine receptor / Monoamine oxidase / Radioligand / Bioimaging / In vivo mapping / Benzodiazepine receptor / Optical isomer |
|---|
| Research Abstract |
Dynamic biological imaging using nuclear medical imaging technique and the radioligand is effective for elucidation of the process of neurotransmission. In this study, the superior radiation properties of 123-I for nuclear medical imaging promoted us to synthesize a radioiodinated compound as a radioligand for imaging. In the molecular design, particular attention was given to optical isomerism since there are cases where a great difference for the affinity for receptors and enzymes is observed between optical isomers. To evaluate the activity of monoamine oxidase (MAO) in vivo, we synthesized a clorgyline analog iodinated at 6-position (6ICG) for MAO A and a Ro 16-6491 analogs iodinated 4-position (4Ro) for MAO B, respectively. Each compound showed a high affinity and selectivity for a corresponding enzyme. Furthermore, a good correlation was observed between the cerebral uptake of radioactivity after injection of radioligand and enzymatic activity. For the imaging of nicotinic cholinergic receptors, a radioiodinated nicotine analog iodinated at 5-position of the pyridine ring,5-iodo-A85380 (5IA) was synthesized and the obtained 5IA was evaluated as a potential radioligand for investigating brain nicotinic receptors. The results of binding affinity experiments revealed that the affinity of 5IA was 10-fold higher than that of (S)-nicotine. Regional cerebral distribution studies in mice and rats disclosed that the accumulation of 125-I-5IA was dense in the thalamus, intermediate in the cortex and less marked in the cerebellum. The marked regional cerebral distribution was reduced and uniformalized by the treatment with cytidine. Gathered data indicate that radioiodinated 6ICG, 4Ro, and 5IA are potential radioligands for in vivo imaging studies of cerebral neurotransmission.
|
