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-RGD环肽二聚体的自动化合成及小动物PET显像

目的 应用国产多功能18F标记模块制备4-[18F]氟-3-三氟甲基苯甲酰基-谷氨酸-(RGD -苯丙氨酸-赖氨酸)环肽二聚体(4-18 F-TFMB-E[c(RGDfk)2]),并用micro PET观察其在肿瘤模型鼠内的生物分布.方法 基于PET-MF-2V-IT-I多功能合成模块,采用“一锅法”完成4-18F-TFMB-E[ c(RGDfk)2]的制备和纯化.荷人胰腺癌BxPC-3裸鼠给药后行micro PET活体显像.结果 4-18 F-TFMB-E[ c(RGDfk)2]放化产率为(27.4±2.3)％(衰减校正后),总合成时间为30 min,无需HPLC法分离,放化纯＞98％.荷人胰腺癌BxPC-3裸鼠注射4-18 F-TFMB-E[c(RGDfk)2]后30、60和120 min后肿瘤摄取值(％ID/g)分别为4.03±0.32、3.31±0.20和2.72±0.17;注射后30 min肿瘤与对侧肌肉摄取值比值大于6(对侧肌肉摄取值为0.47 ±0.12).4-18F-TFMB-E[c (RGDfk)2]主要经肝、肠排泄.结论 4-18F-TFMB-E[ c(RGDfk)2]自动化合成速度快、效率高,胰腺癌肿瘤模型显影清晰.     

23-羟基白桦酸在Caco-2细胞模型中的吸收特性研究

 目的研究23-羟基白桦酸在Caco-2细胞模型中的吸收特性,为设计合理的给药方式提供依据。方法利用MTT实验筛选出23-羟基白桦酸在Caco-2细胞中的安全浓度,然后用Caco-2细胞单层模型研究23-羟基白桦酸的双向转运,采用同位素示踪法检测药物浓度,计算其表观渗透系数,考察时间、药物浓度对23-羟基白桦酸吸收的影响。结果23-羟基白桦酸在Ca- co-2细胞模型中的转运中对应时间点表观渗透系数值(P_app)A→B约等于(P_app)B→A,随时间增加P_app逐渐下降,而在所测浓度范围内P_app值基本保持恒定。结论23-羟基白桦酸在Caco-2细胞模型中的吸收机制主要是被动转运。     

(S)-1-烯丙基-2-氨甲基吡咯烷的制备

（S）-1-烯丙基-2-氨甲基吡咯烷（1）是制备新型多巴胺D2-受体正电子发射断层扫描（PET）显像剂18^F-fallypride的中间体。本研究参考文献，用L-脯氨酰胺（2）经烯丙基化、还原制得1（图1），并进行了改进。用烯丙基溴代替价昂且不稳定的烯丙基碘反应制得（S）-l-烯丙基吡咯烷酰胺（3），收率92％（文献：70％）；用LiAlH4在0℃还原（文献：用DIBALH在-78℃反应）后，回流反应24h制得1，操作简便。改进后的1总收率大于50％。     

^18F-fallypride-新型多巴胺受体显像剂在脑神经疾病研究中的临床应用

^18F-Fallypride是一种新型安全的多巴胺D2受体PET显像剂,具有亲和力高、亲脂性适宜、半衰期短等特点,本文综述^18F-Fallypride用于精神分裂症、癫痫、抽动秽语综合征、兴奋剂成瘾性等的多巴胺D2/D3受体变化的研究。     

N- 18F-氟乙基-托法替尼的制备及其在类风湿关节炎显像中的研究

目的:制备探针 N- 18F-氟乙基-托法替尼,探讨其用于类风湿关节炎(RA)诊疗的可行性。 方法:采用"两步法"对托法替尼进行 18F-氟乙基修饰,应用高效液相色谱(HPLC)对探针的标记率和放化纯进行测定,并考察探针的体内外稳定性。BABL/c小鼠(正常组; ...     

2480 WIZARD2珈玛计数器测量正电子核素^68Ga的应用研究

目的建立2480 WIZARD2珈玛计数器测定68Ga放射性活度的方法。方法制备68Ga贮备液（3.7×107Bq/mL）。倍比稀释后,用PE公司2480 WIZARD2珈玛计数器测定活度,建立标准曲线,对测量时间、精密度、重复性、稳定性及测量效率等进行研究。结果 2480 WIZARD2珈玛计数器的测量时间优选为5 s。68Ga活度在18.5~3.7×104Bq范围内线性关系良好,回归方程为：y（cpm）=24.67x（Bq）,r=0.9999。最低检测限为3.7 Bq,计数器本底值为（142±49）cpm。精密度、重复性与稳定性试验的RSD分别为0.86%,0.70%和0.71%。珈玛计数器的测量效率为（41.04±0.95）%。结论该法操作简单、快速、准确且灵敏,适用于68Ga的放射性活度测定。     

SPECT显像剂埘131I-Nalepride的合成

5-碘-2，3-二甲氧基苯甲酸与（S）-1-烯丙基-2-氨甲基吡咯烷反应得到（S）-（-）-N-[（1-烯丙基-2-吡咯烷基）甲基]-2,3-二甲氧基-5-碘苯甲酰胺，与双三丁基锡反应得到标记前体（S）-（-）-M[（1-烯丙基-2-吡咯烷基）甲基]-2，3-二甲氧基-5-三丁基锡苯甲酰胺，总收率约70％。用双氧水法对标记前体进行碘[131↑I]标记得到SPECT显像剂131↑I-nalepride，标记率和放射化学纯度分别为95．4％和96．3％。     

靶向整合素αvβ3探针用于甲状腺乳头状癌显像的研究

目的 制备特异性整合素αvβ3探针[^18F]氟化铝-匹仑吉肽（^18F-Al-NOTA-PRGD2）,探讨其用于甲状腺乳头状癌（PTC） PET显像的可行性.方法 采用氟化铝新策略制备18F-Al-NOTA-PRGD2.取新鲜切除的人PTC肿瘤组织接种于裸鼠右腋下,制得荷人PTC裸鼠模型.再分别取人PTC标本及毗邻的正常组织、荷瘤裸鼠移植瘤行整合素αvβ3免疫组织化学染色.荷瘤裸鼠（n=5）尾静脉注射1.1 MBq ^18F-Al-NOTA-PRGD2后30、60和120 min分别行microPET显像,通过ROI技术计算肿瘤和主要脏器的放射性摄取值（％ ID/g）,并通过阻断实验验证其特异性.另取15只荷瘤裸鼠研究其注药后30、60及120 min生物分布,计算放射性摄取值（％ID/g）.用两样本t检验进行统计学处理.结果 成功制备^18F-Al-NOTA-PRGD2,标记率＞45％.免疫组织化学染色证实人PTC标本和裸鼠移植瘤组织整合素αvβ3染色均呈棕褐色阳性表达,人PTC毗邻正常组织不表达.荷瘤裸鼠注射^18 F-Al-NOTA-PRGD2后行microPET显像示,肿瘤清晰可见,且与周围组织对比度良好.注射后30、60、120 min肿瘤对显像剂的摄取值分别为（2.81±0.35）、（2.45±0.27）和（1.80±0.21） ％ID/g.PRGD2阻断后,注射^18F-Al-NOTA-PRGD2后60 min肿瘤对显像剂的摄取值降为（0.51±0.05） ％ID/g.荷瘤裸鼠生物分布实验示,注射显像剂后30、60、120 min肿瘤摄取值分别为（3.09±0.25）、（2.75±0.37）和（1.90±0.16） ％ID/g,与microPET显像基本一致（t=1.456、1.465和0.847,均P＞0.05）.^18F-Al-NOTA-PRGD2在血液和肌肉中清除快,注射后60 min肿瘤与血液和肌肉的摄取比值分别为6.15±0.45和7.86±0.56.结论 ^18F-Al-NOTA-PRGD2制备简单,放化纯高,可有效监测PTC中整合素αvβ3表达水平;其PET显像有望为研究PTC整合素αvβ3受体相关机制提供一种新方法.     

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.