放射合成
转运蛋白
化学
产量(工程)
放射性配体
高效液相色谱法
比活度
去甲基
化学合成
核化学
放射化学
正电子发射断层摄影术
代谢物
色谱法
有机化学
核医学
生物化学
材料科学
医学
内科学
神经炎症
冶金
体外
炎症
酶
结合位点
作者
Min Wang,Mingzhang Gao,Kathy D. Miller,Qi Zheng
出处
期刊:Steroids
[Elsevier]
日期:2011-11-01
卷期号:76 (12): 1331-1340
被引量:59
标识
DOI:10.1016/j.steroids.2011.06.012
摘要
The translocator protein 18 kDa (TSPO) is an attractive target for molecular imaging of neuroinflammation and tumor progression. [18F]PBR06, a fluorine-18 labeled form of PBR06, is a promising PET TSPO radioligand originally developed at NIMH. [11C]PBR06, a carbon-11 labeled form of PBR06, was designed and synthesized for the first time. The standard PBR06 was synthesized from 2,5-dimethoxybenzaldehyde in three steps with 71% overall chemical yield. The radiolabeling precursor desmethyl-PBR06 was synthesized from 2-hydroxy-5-methoxybenzaldehyde in five steps with 12% overall chemical yield. The target tracer [11C]PBR06 was prepared by O-[11C]methylation of desmethyl-PBR06 with [11C]CH3OTf in CH3CN at 80 °C under basic condition and isolated by HPLC combined with SPE purification with 40–60% decay corrected radiochemical yield and 222–740 GBq/μmol specific activity at EOB. On the similar grounds, [18F]PBR06 was also designed and synthesized. The previously described Br-PBR06 precursor was synthesized from 2,5-dimethoxybenzaldehyde in two steps with 78% overall chemical yield. A new radiolabeling precursor tosyloxy-PBR06, previously undescribed tosylate congener of PBR06, was designed and synthesized from ethyl 2-hydroxyacetate, 4-methylbenzene-1-sulfonyl chloride, and N-(2,5-dimethoxybenzyl)-2-phenoxyaniline in four steps with 50% overall chemical yield. [18F]PBR06 was prepared by the nucleophilic substitution of either new tosyloxy-PBR06 precursor or known Br-PBR06 precursor in DMSO at 140 °C with K[18F]F/Kryptofix 2.2.2 for 15 min and HPLC combined with SPE purification in 20–60% decay corrected radiochemical yield, >99% radiochemical purity, 87–95% chemical purity, and 37–222 GBq/μmol specific activity at EOB. Radiosynthesis of [18F]PBR06 using new tosylated precursor gave similar radiochemical purity, and higher specific activity, radiochemical yield and chemical purity in comparison with radiosynthesis using bromine precursor.
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