ポジトロン断層法によるヒト脳ドーパミン代謝測定へのF-18標識プロドラッグの応用
| Project/Area Number |
04670714
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Psychiatric science
|
|---|
| Research Institution | Tokyo Metropolitute of Gerontology |
|---|
Principal Investigator |
ISHIWATA Kichi Tokyo Metropolitan Institute of Gerontology, Positron Medical Center, Senior Researsh Scientist, ポジトロン医学研究部門, 主任研究員 (50143037)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
ISHII Kenji Tokyo Metropolitan Institue of Gerontology, Positron Medical Center. Reserch Sci, ポジトロン医学研究部門, 研究員 (10231135)
SENDA Michio Tokyo Metropolitan Institute of Gerontology, Positron Medical Center, Chief of D, ポジトロン医学研究部門, 副参事研究員 (00216558)
|
|---|
| Project Period (FY) |
1992 – 1993
|
| Project Status |
Completed (Fiscal Year 1993)
|
| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1993: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1992: ¥1,500,000 (Direct Cost: ¥1,500,000)
|
|---|
| Keywords | dopamine metabolism / fluorodopa / radiopharmaceutical / positron emission tomography / nuclear medicine / プロドラッグ |
|---|
| Research Abstract |
The potential of a fluorinated dopa prodrug as a tracer for studying presynaptic dopamine metabolism by PET was evaluaed in vivo. 6-[^<18>F]fluoro-O-pivaloyl-L-dopa (6-[^<18>F]FPDOPA) was prepared by direct fluorination of 4-O-pIVALOYl-L-dopa with acetyl [^<18>F]hypofluorite. In mice, brain uptake of the compound was lower than that of 6-[^<18>F]FDOPA ; however, the uptake ratios of striatum-to-other reference regions was larger in the 6-[^<18>F]FPDOPA than in the 6-[^<18>F]fdopa. Inhibitors of aromatic amino acid decarboxylase and catechol-O-methyl transferase enhanced selective uptake by the striatum ; the effect was smaller for 6-[^<18>F]FPDOPA than for 6-[^<18>F]FDOPA.reduced brain uptake of both compounds by L-phenylalanine-loading suggested that transport of the compounds across the blood-brain barrier was mediated by the neutral amino acid transoport system. BY HPLC analysis, 6-[^<18>F]FPDOPA, 6-[^<18>F]FDOPA, 6-[^<18>F]fluorodopamine and other metabolies were found in the striatum, although 6-[^<18>F]fluorodopamine was not found in other brain regions. The results show the potential of 6-[^<18>F]FPDOPA as a dopa prodrug.
The HCl-hydrysis of 6-[^<18>F]FPDOPA followed by HPLC separation using the buffered physiological saline as an eluting solution, gave a steril and apyrogenic 6-[^<18>F]FDOPA injection. The method was suitable for routine production in human PET studies as compared to the methods reported prevously. In human PET studies using 6-[^<18>F]FDOPA, the metabolic images of the brain obtained by PET were superimposed precicely to the structual images obatined by MRI, has been developed. Semi-quantitative assesment of doamine metabolism in the striatum has been performed in normal subjects.
|
Report
(3 results)
Research Products
(7 results)
