18F-FECNT的生物分布特性及小动物PET显像研究

Objective 2β-carbomethoxy-3β-(4-corophenyl)-8-(2-18F-fluoroethyl) nortropane (18F-FECNT) is a recently developed dopamine transporter (DAT) imaging agent. The aim of this study was to evaluate its brain biedistribution and to assess its usefulness in quantitation of DAT density in normal and hemiparkinsonian rats. Methods Six groups of mice (5 mice each group) received 18F-FECNT were sacri-ficed at indicated time post injection. Different brain regions (cortex, hippocampus, striatum, cerebellum) were removed, weighed, and countered. DAT blocking effect was investigated in mice pretreated with 2β-Carbomethoxy-3β-(4-fluorpbenyl)tropane (β-CFT) at before 18F-FECNT injection. MicroPET scans were performed in beth normal and unilaterally 6-hydroxydopamine-lesioned rats. Results The brain uptake of 18F-FECNT was 2.22, 1.20, 1.02, 0.78, 0.71, and 0.67 percent injection dose (%ID) at 5, 15, 30, 60, 120, and 180 min post injection. Radioactivity concentration of the striatum, the target region, was the highest in the brain regions and decreased quickly from 5 to 60 min and reached to background at 120 min of post injection. The striatum/cerebellum ratio was 2.56, 3.47, 2.78, 1.63, 0.97, and 0.88 at 5, 15, 30, 60, 120, and 180 min, respectively, post injection. The selective striatum uptake of 18F-FECNT decreased dramatically to the background when the DAT was blocked with β-CFT. The striatum of normal rats in micro-PET exhibited symmetrical (left/right = 1.00±0.05) and the highest uptake of radioactivity (striatum/cere-helium =2.18±0. 16 at 5- 125 min, n =3). As for the hemiparkinsonian rats, nonsymmetrical [unlesioned striatum/cerebellum vs lesioned striatum/cerebellum = 2.01 ± 0.23 (n = 3) vs 1.04 ± 0. 05] and the high-est uptake of radioactivity were also noted. Conclusions The results suggest that 18F-FECNT rapidly pas-ses through blood-brain barrier and locates in stiatal region with high affinity and selectivity to DAT. It is a potential radiotracer to assess the in vivo DAT density in Parkinson's disease.     

MicroPET显像测定小鼠心肌葡萄糖摄取及代谢率的实验条件分析

目的 建立适合的microPET测定小鼠心肌葡萄糖代谢率(MRGlu)的实验方法和条件,并评价该方法的可行性.方法 控制温度在30～ 34℃,取正常进食的野生型BKS小鼠20只,按随机数字表法分为不同异氟烷体积分数(1.3％、1.5％、1.8％和2.0％)麻醉组,观察小鼠呼吸频率及存活状态,获得最佳浓度;另取BKS小鼠20只,在最佳异氟烷浓度麻醉下,注射不同体积(0、75、150、300 μl)生理盐水,观察各组小鼠血糖变化,获得最适宜注射体积.取BKS小鼠6只,在最佳异氟烷浓度麻醉下,注射最适宜体积18 F-FDG,对小鼠心肌行microPET显像,通过勾画ROI获取心肌TAC,计算SUV.同时,经小鼠尾静脉多点采血获取尾静脉TAC,利用输入函数数学模型显像分析系统,获得代谢速率常数k1,k2,k3,k4,计算心肌MRGlu:MRGlu=Ki ×Glu/LC[Ki=k1×k3/(k2+k3),Glu为平均血糖浓度,LC为集总常数(心肌取1)].数据比较采用单因素方差分析和q检验.结果 小鼠在正常进食的情况下,以体积分数1.5％～1.8％异氟烷麻醉,小鼠呼吸频率在80次/min以上,无任何体位移动.注射生理盐水75μl组小鼠在不同时间点的血糖与不注射生理盐水相比,差异均无统计学意义(F=1.215,P＞0.05).150μl组小鼠血糖在30 min(q=2.485,P=0.024)、45 min(q=2.287,P=0.036)、60 min(q=2.709,P=0.015)与0μl组差异均有统计学意义;300ul组小鼠血糖在45 min(q=2.435,P=0.027)与0山组差异有统计学意义.18F-FDG注射体积≤75止、剂量为7.4～11.1 MBq时,micro-PET显像可获得小鼠相对接近生理状态下的清晰稳定图像,45～55 min小鼠心肌SUV中位数为11.88(范围9.71～14.93),K值中位数为0.19(范围0.10～0.54) ml·min-1·g-1,MRGlu值中位数为19.64(范围5.55～23.28) mg·kg-1· min-1.结论 在microPET18F-FDG显像评估小鼠心肌葡萄糖摄取及代谢率过程中,适宜异氟烷麻醉体积分数为1.5％～1.8％,18F-FDG注射体积需≤75 μl;该方法切实可行.     

nor-β-CFT的HPLC测定

建立了nor-β-CFT含量的HPLC测定法.采用Lichrospher C18色谱柱,以甲醇-水(75:25)为流动相,检测波长254nm.在浓度0.2～1.2mg/ml范围内线性关系良好(r＝0.9997).方法平均回收率为99.6%,RSD为0.71%.     

TRODAT-1冻干品稳定性探讨

目的 :研究TRODAT 1冻干品的稳定性。方法 :经光照、高温、高湿、加速、室温留样、低温(- 18°C)条件放置 ,测定其标记率及pH值。结果 :在光照、高湿度下 ,标记率及 pH值均没有明显变化 ;(4 1.0±s1.0 )°C的高温下 ,标记率有明显降低 ;室温下 3mo内稳定 ;加速条件下 2mo内稳定。结论 :TRODAT 1冻干品对光、湿稳定 ,对热不稳定 ,应保存在冰箱冷冻室中 ,在此条件下 ,有效期至少 1a ,能满足常规临床要求。     

实验性高眼压对兔睫状体多巴胺转运体和多巴胺D2受体的影响

目的研究兔实验性高眼压对睫状体多巴胺能系统的影响.方法将新西兰兔随机分为3组:实验A组于前房内注射复方卡波姆溶液0.1 ml,实验B组于前房内注射等量生理盐水,对照组不作前房注射.每日测量眼压,共1周.利用放射性配体125I-epidepride多巴胺D2(DAD2)显像剂、99mTc-TRODAT-1多巴胺转运体(DAT)显像剂,结合放射自显影技术观察兔虹膜睫状体内的DAD2受体(DAD2R)和DAT含量.结果实验A组虹膜睫状体DAD2R特异性放射性摄取比值(3.8231±0.6487)较对照组(6.3949±0.7780)下降67.27%(P＜0.05);DAT特异性放射性摄取比值(10.4431±1.2430)较对照组(16.2321士0.5939)下降35.66%(P＜0.05);而对照组与实验B组DAD2R、DAT特异性放射性摄取比值的差异无显著性(P＞0.05).结论高眼压时实验兔睫状体多巴胺能系统受到损害.     

18F-FECNT的生物分布特性及小动物PET显像研究

Objective 2β-carbomethoxy-3β-(4-corophenyl)-8-(2-18F-fluoroethyl) nortropane (18F-FECNT) is a recently developed dopamine transporter (DAT) imaging agent. The aim of this study was to evaluate its brain biedistribution and to assess its usefulness in quantitation of DAT density in normal and hemiparkinsonian rats. Methods Six groups of mice (5 mice each group) received 18F-FECNT were sacri-ficed at indicated time post injection. Different brain regions (cortex, hippocampus, striatum, cerebellum) were removed, weighed, and countered. DAT blocking effect was investigated in mice pretreated with 2β-Carbomethoxy-3β-(4-fluorpbenyl)tropane (β-CFT) at before 18F-FECNT injection. MicroPET scans were performed in beth normal and unilaterally 6-hydroxydopamine-lesioned rats. Results The brain uptake of 18F-FECNT was 2.22, 1.20, 1.02, 0.78, 0.71, and 0.67 percent injection dose (%ID) at 5, 15, 30, 60, 120, and 180 min post injection. Radioactivity concentration of the striatum, the target region, was the highest in the brain regions and decreased quickly from 5 to 60 min and reached to background at 120 min of post injection. The striatum/cerebellum ratio was 2.56, 3.47, 2.78, 1.63, 0.97, and 0.88 at 5, 15, 30, 60, 120, and 180 min, respectively, post injection. The selective striatum uptake of 18F-FECNT decreased dramatically to the background when the DAT was blocked with β-CFT. The striatum of normal rats in micro-PET exhibited symmetrical (left/right = 1.00±0.05) and the highest uptake of radioactivity (striatum/cere-helium =2.18±0. 16 at 5- 125 min, n =3). As for the hemiparkinsonian rats, nonsymmetrical [unlesioned striatum/cerebellum vs lesioned striatum/cerebellum = 2.01 ± 0.23 (n = 3) vs 1.04 ± 0. 05] and the high-est uptake of radioactivity were also noted. Conclusions The results suggest that 18F-FECNT rapidly pas-ses through blood-brain barrier and locates in stiatal region with high affinity and selectivity to DAT. It is a potential radiotracer to assess the in vivo DAT density in Parkinson's disease.     

18F-FECNT的生物分布特性及小动物PET显像研究

Objective 2β-carbomethoxy-3β-(4-corophenyl)-8-(2-18F-fluoroethyl) nortropane (18F-FECNT) is a recently developed dopamine transporter (DAT) imaging agent. The aim of this study was to evaluate its brain biedistribution and to assess its usefulness in quantitation of DAT density in normal and hemiparkinsonian rats. Methods Six groups of mice (5 mice each group) received 18F-FECNT were sacri-ficed at indicated time post injection. Different brain regions (cortex, hippocampus, striatum, cerebellum) were removed, weighed, and countered. DAT blocking effect was investigated in mice pretreated with 2β-Carbomethoxy-3β-(4-fluorpbenyl)tropane (β-CFT) at before 18F-FECNT injection. MicroPET scans were performed in beth normal and unilaterally 6-hydroxydopamine-lesioned rats. Results The brain uptake of 18F-FECNT was 2.22, 1.20, 1.02, 0.78, 0.71, and 0.67 percent injection dose (%ID) at 5, 15, 30, 60, 120, and 180 min post injection. Radioactivity concentration of the striatum, the target region, was the highest in the brain regions and decreased quickly from 5 to 60 min and reached to background at 120 min of post injection. The striatum/cerebellum ratio was 2.56, 3.47, 2.78, 1.63, 0.97, and 0.88 at 5, 15, 30, 60, 120, and 180 min, respectively, post injection. The selective striatum uptake of 18F-FECNT decreased dramatically to the background when the DAT was blocked with β-CFT. The striatum of normal rats in micro-PET exhibited symmetrical (left/right = 1.00±0.05) and the highest uptake of radioactivity (striatum/cere-helium =2.18±0. 16 at 5- 125 min, n =3). As for the hemiparkinsonian rats, nonsymmetrical [unlesioned striatum/cerebellum vs lesioned striatum/cerebellum = 2.01 ± 0.23 (n = 3) vs 1.04 ± 0. 05] and the high-est uptake of radioactivity were also noted. Conclusions The results suggest that 18F-FECNT rapidly pas-ses through blood-brain barrier and locates in stiatal region with high affinity and selectivity to DAT. It is a potential radiotracer to assess the in vivo DAT density in Parkinson's disease.     

多巴胺转运蛋白显像剂18F-FP-β-CIT制备与分布

目的　探讨简易制备和纯化多巴胺转运蛋白 (DAT)显像剂1 8F N (3 氟丙基 ) 2 β 甲酯基 3β (4′ 碘苯基 )去甲基托烷 (1 8F FP β CIT)的方法 ,进行大鼠脑内分布研究。方法　采用一步法标记 ,在氨基聚醚 (Kryptofix 2 2 2 )催化下 ,标记前体化合物N 3 (甲磺酰氧基丙基 ) 2 β 甲酯基 3β (4 碘苯基 )去甲基托烷 (MsOP CIT)直接与K1 8F在乙腈溶液中反应 ,生成1 8F FP β CIT ,用Sep PakSiO2 小柱分离纯化。大鼠给药后于不同时间处死 ,分离脑组织 ,分别称重后测定放射性计数。结果　1 8F FP β CIT总放化产率约为 10 % ,放化纯 >95 % ,纯化无需制备型高效液相色谱。总合成时间为 6 0～ 80min。药物能迅速被脑组织摄取 ,后不断清除 ,5和 180min时全脑摄取量 (%ID)分别为 1.4 9和 0 .17。纹状体放射性摄取大于其他区域 ,其与小脑的比值在 5、30、6 0、12 0和 180min时分别为 1.75、3.38、3.73、3.71和 3.2 0。结论　一步法可简便制得1 8F FP β CIT。     

^18F-FECNT的生物分布特性及小动物PET显像研究

目的探讨多巴胺转运蛋白（DAT）显像剂^18F-N-（2-氟乙基）-2β-甲酯基-3β-（4-氯苯基）去甲基托烷（FECNT）的体内生物分布特性,并进行小动物PET显像研究,以评价其临床应用潜力。方法自制^18F-FECNT注射液,进行正常小鼠脑内分布、DAT阻断实验、正常和单侧帕金森病（PD）模型大鼠小动物PET脑显像。结果正常ICR小鼠在给药后5,15,30,60,120,180min的进脑量分别达2．22,1．20,1．02,0．78,0．71,0．67百分注射剂量率（％ID）。给药后5～60min内,药物在纹状体（ST）部位浓聚,纹状体／小脑（ST／CB）比值在5,15,30,60min时分别为2．56,3．47,2．78,1．63。120min后ST的放射性浓度下降至与其他脑组织相近。脑内DAT经β-CFF阻断的小鼠,其ST未见放射性浓聚。正常大鼠小动物PFT显像图中ST显影清晰（ST／CB=2．18±0．16,n=3）,双侧对称;PD模型大鼠未损毁侧ST放射性浓聚（ST未损毁侧／CB=2．01±0．23,n=3）,而损毁侧ST放射性摄取不明显,与小脑相当（ST损毁侧／CB=1．04±0．05）。结论^18F-FECNT能透过无损的血脑屏障浓聚于ST,对DAT具有高亲和性与特异性,是一种有临床应用潜力的DAT显像剂。     

18F-FECNT的生物分布特性及小动物PET显像研究

Objective 2β-carbomethoxy-3β-(4-corophenyl)-8-(2-18F-fluoroethyl) nortropane (18F-FECNT) is a recently developed dopamine transporter (DAT) imaging agent. The aim of this study was to evaluate its brain biedistribution and to assess its usefulness in quantitation of DAT density in normal and hemiparkinsonian rats. Methods Six groups of mice (5 mice each group) received 18F-FECNT were sacri-ficed at indicated time post injection. Different brain regions (cortex, hippocampus, striatum, cerebellum) were removed, weighed, and countered. DAT blocking effect was investigated in mice pretreated with 2β-Carbomethoxy-3β-(4-fluorpbenyl)tropane (β-CFT) at before 18F-FECNT injection. MicroPET scans were performed in beth normal and unilaterally 6-hydroxydopamine-lesioned rats. Results The brain uptake of 18F-FECNT was 2.22, 1.20, 1.02, 0.78, 0.71, and 0.67 percent injection dose (%ID) at 5, 15, 30, 60, 120, and 180 min post injection. Radioactivity concentration of the striatum, the target region, was the highest in the brain regions and decreased quickly from 5 to 60 min and reached to background at 120 min of post injection. The striatum/cerebellum ratio was 2.56, 3.47, 2.78, 1.63, 0.97, and 0.88 at 5, 15, 30, 60, 120, and 180 min, respectively, post injection. The selective striatum uptake of 18F-FECNT decreased dramatically to the background when the DAT was blocked with β-CFT. The striatum of normal rats in micro-PET exhibited symmetrical (left/right = 1.00±0.05) and the highest uptake of radioactivity (striatum/cere-helium =2.18±0. 16 at 5- 125 min, n =3). As for the hemiparkinsonian rats, nonsymmetrical [unlesioned striatum/cerebellum vs lesioned striatum/cerebellum = 2.01 ± 0.23 (n = 3) vs 1.04 ± 0. 05] and the high-est uptake of radioactivity were also noted. Conclusions The results suggest that 18F-FECNT rapidly pas-ses through blood-brain barrier and locates in stiatal region with high affinity and selectivity to DAT. It is a potential radiotracer to assess the in vivo DAT density in Parkinson's disease.