摘要
目的 研究正电子断层显像剂 2 18F 2 脱氧 D 葡萄糖 (18F FDG)的合成改进及其小鼠体内药动学。方法 采用回旋加速器通过核反应18O(p ,n) 18F生产18F-,18F-在相转移催化剂Kryptofix 2 2 2存在下与前体 1,3,4,6 四乙酰基 2 三氟磺酰甲基 β D(+)甘露糖发生亲核取代反应 ,经水解、中和、纯化得18F FDG注射液。建立其质量控制方法 ,并测定其药动学参数和体内生物分布。结果 经时间衰减校正后 ,18F FDG放射化学产率约为 72 % ,总合成时间为 5 0min ,各项质量控制指标符合美国药典要求。18F FDG的药动学符合三室模型 ,分布相半衰期分别为t1/ 2π(0 .4min)和t1/ 2α(4 .8min) ,消除相半衰期为t1/ 2 β(85 .4min)。18F FDG在小鼠心肌和脑中有较高的摄取率及较高的心 非靶器官和脑 非靶器官比 ,且放射性持续时间较长 ,并通过肾脏迅速排出 ;注入18F FDG 45min后 ,放射性在血和各脏器中的分布逐渐达到平衡。正常人体内分布实验结果与肺癌患者相类似 ,但肺癌患者体内有很高的肿瘤 正常组织的放射性比值。结论 制备的18F
OBJECTIVE To modify the synthesis of 2-deoxy-2- 18F-fluoro-D-glucose ( 18F-FDG) as a positron emission tomography (PET) imaging agent and to study its pharmacokinetics in mice.METHODS 18F-FDG injection was synthesized via nucleophilic substitution reaction of 18F - produced by the nuclear reaction 18O(p,n) 18F in PETtrace Cyclotron with precursor 1,3,4,6-tetra-O-trifluoro-methanesulfonyl-β-D-mannopyranose in the presence of the Kryptofix 222 as a phase-transfer catalyst after hydrolysis, neutralization, and purification.Its pharmacokinetic parameters in mice and biodistribution in mice or man were determined after quality control of 18F-FDG was finished.RESULTS The corrected radiochemical yield of 18F-FDG was about 72%,the whole synthesis time was 50 min, and the radiochemical purity was above 95% by HPLC and TLC respectively.All quality criteria of 18F-FDG met the requirements of the pharmacopoeia of USA.The pharmacokinetic characteristics of 18F-FDG conformed to a three-compartment model, and the main parameters were t 1/2π(0.4 min),t 1/2α(4.8 min),t 1/2β(85.4 min),respectively. The biodistribution of 18F-FDG in mice showed that the higher uptake rates of 18F-FDG in heart and brain, and the higher heart to nontarget organs and brain to nontarget organs ratios were found.The radioactivity in heart and brain remained longer time, but the radioactivity in kidney was rapidly cleared. The radioactivity in blood and organs slowly ran up to relatively constant after 45 min postinjection of 18F-FDG. The biodistributions of 18F-FDG in healthy volunteers were similar to those in patients with lung cancer, however, the higher tumor to normal organs ratios were observed in patients with lung cancer.CONCLUSION The synthesized FDG can be used for PET study and clinical diagnosis.
出处
《中国药学杂志》
EI
CAS
CSCD
北大核心
2002年第4期287-290,共4页
Chinese Pharmaceutical Journal
