| Project/Area Number |
09670913
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Radiation science
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| Research Institution | Tohoku University |
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Principal Investigator |
IWATA Ren Cyclotron & Radioisotope Center, Tohoku University Associate Professor, サイクロトロンRIセンター, 助教授 (60143038)
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| Co-Investigator(Kenkyū-buntansha) |
YANAI Kazuhiko School of Medicine, Tohoku University Professor, 医学部, 教授 (50192787)
IDO Tatsuo Cyclotron & Radioisotope Center, Tohoku University Professor, サイクロトロンRIセンター, 教授 (80134063)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Histamine receptor / Fluorobenzyl halide / positron emitter / PET / Radiopharmaceutical / Fluorine-18 / Fluoroproxyfan / Radioligand |
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| Research Abstract |
A new, useful positron emitting radioligand, [^<18>F]fluoroproxyfan (3-(1H-Imidazol-4-yl)propyl 4-[^<18>F]fluorobenzyl ether), was successfully prepared from 4-[^<18>F]fluorobenzyl halide for imaging of histamine 113 receptors and preliminarily evaluated for its affinity and selectivity to the receptors.
4-[^<18>F]Fluorobenzaldehyde, synthesized from [^<18>F]fluoride by aromatic nucleophilic substitution on 4-trimethylammoniumbenzaldehyde triflate, was first retained on a C18 cartridge and there efficiently reduced to 4-[^<18>F]fluorobenzyl alcohol simply by flowing an aqueous solution of NaBH_<4-> 4-[^<18>F]Fluorobenzyl alcohol was efficiently converted to 4-[^<18>F]fluorobenzyl halide using P_2I_4 or Ph_3PBr_2 in GH_2Cl_2. The conversion rapidly proceeded in radiochemical yields of nearly 90% at 40ﾟC with P_2I4 and almost quantitatively at room temperature with Ph_3PBr_2- With this last reagent 4-['8F]fluorobenzyl bromide was obtained in overall radiochemical yields of 45-55% within 30 mm from EOB.This method is expected to be suitable for automated preparation of 4-[^<18>F]fluorobenzyl halides from [^<18>F]fluoride.
[^<18>F]Trityl-fluoroproxyfan was synthesized in around 25% radiochemical yields from 4-[^<18>F]fluoro-benzyl bromide using silver triflate under mild reaction conditions. The crude product was purified with a silica gel cartridge and then hydrolyzed into [^<18>F]fluoroproxyfan with 50% HCOOH.[^<18>F]Fluoroproxyfan was obtained in 10% overall radiochemical yields within 2 hrs from EOB.
The binding of [^<18>F]fiuoroproxyfan to the membranes of rat forebrain was found to be stereoselective, saturable, reversible and temperature-dependent. it was also increased in the rat brain following 6-hydroxydopamine injection to substantia nigra. These data suggest that [^<18>F]fluoroproxyfan is a potential ligand for imaging "supersensitivity" induced by dopaminergic denervation.
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