11C-(-)间羟基麻黄素的合成及Micro PET显像

摘要

11C标记(-)间羟基麻黄素(11C-(-)HED,11C-HED)是一种交感神经系统显像剂,可用于心肌和肾上腺肿瘤的显像.碘代甲烷与(-)间羟胺直接甲基化反应,生成11C-HED,经HPLC梯度淋洗纯化；通过动物实验研究在11C-HED中添加前体后对心肌摄取的影响.结果表明,用碘代甲烷作甲基化试剂可减少副反应,分别用含3％乙醇和10％乙醇的0.24 mol/L磷酸二氢钠溶液梯度淋洗,能有效去除前体间羟胺,同时放化纯度从93.2％提高到98％.11 C-HED在动物体内的生物分布表明,注射含2 mg/kg前体间羟胺的11 C-HED后,30 min时心肌摄取明显降低,而肾上腺摄取增高.Micro PET显像证实,注射11C-HED后正常心肌显像,但加入前体后心肌摄取降低,清除加快.以上结果提示,分别用含3％和10％乙醇的0.24 mol/L磷酸二氢钠溶液梯度淋洗可提高产品化学纯度和放化纯度；在11C-HED中加入前体间羟胺后对心肌摄取明显降低,而肾上腺摄取增高.%11C-meta-(-)Hydroxyephedrine(11C-(-) HED, 11C-HED) is a radiotracer suitable for mapping human sympathetic nervous system for heart failure, heart transplantation, arrhythmia and diabetic autonomic neuropathy and imaging tumors of the adrenal marrow. 11C-HED was synthesized by direct N-methylation of metaraminol with the 11C-methy-iodine and purified by semi-preparative reversed-phase HPLC(Semi-HPLC). The uptake of myocardium was studied by co-injection of 11C-(-)HED with metaraminol in mice. The results showed that the by-products can be reduced with 11C-methy-iodine as the N-methylation a-gents. HPLC purification was started with 3% EthOH in 0. 24 moL/L NaH2PO4, and then switched to 10% EthOH in 0. 24 moL/L NaH2PO4 after 10 min, through this process theprecursor was speparated from 11C-HED. Results of biodistribution showed that the uptake of 11C-HED in heard was blocked by co-injection of the metaraminol at 2 mg/kg, but the ID/'o/g of adrenals was increased. Micro PET imaging showed that the heart can be visualized at 10 and 30min postinjection, but the uptake of myocardium was decreased and the washout was speeded after co-injection of the precursor. The chemical and radiochemical purity of -C-(-)HED can be improved by using 3% EthOH in 0. 24 moL/L NaH2PO4 and then switching to 10% EthOH in 0. 24 moL/L NaH2PO4 as the HPLC mobile phase.