The ligand of N-(3-fluoropropyl)-2β-carbomethoxy-3β-(4’-iodophenyl) nortropane (FP-β-CIT) and mesylate precursor were synthesized by hydrolysis of cocaine, followed by dehydration, esterification, Grignard reactio...The ligand of N-(3-fluoropropyl)-2β-carbomethoxy-3β-(4’-iodophenyl) nortropane (FP-β-CIT) and mesylate precursor were synthesized by hydrolysis of cocaine, followed by dehydration, esterification, Grignard reaction, N-demethylation, iodination, N-alkylation with 3-bromopropanol and methylsulfonylation. Finally, 18F-FP-β-CIT was prepared by nucleophilic fluorination of the mesylate with K18F/K2.2.2 (Kryptofix). The labeling yield of 18F-FP-β-CIT is 25%~30%. The total radiochemical yield of this compound, calculated from the end of bombardment (EOB) with decay correction, is 10%~12% with a synthesis time of 100~110.min. The radiochemical purity of 18F-FP-β-CIT is greater than 90%, and this compound in aqueous solution is also stable for more than 4 hours at room temperature. It is stable enough for clinical study.展开更多
The paper is to study pharmacologic characteristics of 18F-FP-β-CIT (18F-N-(3-fluoropropyl)-2β-carbomethoxy-3β- (4-iodophenyl)nortropane) as an imaging agent for dopamine transporter. The radiochemical purity of 18...The paper is to study pharmacologic characteristics of 18F-FP-β-CIT (18F-N-(3-fluoropropyl)-2β-carbomethoxy-3β- (4-iodophenyl)nortropane) as an imaging agent for dopamine transporter. The radiochemical purity of 18F-FP-β-CIT in aqueous solution was over 95% after standing at room temperature for 4h. Biodistribution displayed rapid uptake in rat brain (1.375 %ID/organ at 5min and 0.100 %ID/organ at 180 min) and the striatal uptake was 1.444, 0.731, 0.397, 0.230 and 0.146 %ID/g at 5, 30, 60, 120 and 180 min, respectively. The values of striatum/cerebellum, striatum /frontal cortex and striatum / hippocampus in rat's brain at 30 min were 3.38, 2.17 and 2.40 respectively. The uptake in striatum can be blocked by β-CFT, suggesting that 18F-FP-β-CIT binds to DAT peculiarly. The compound was rapidly cleared from monkey's blood. The striatal uptake was bilaterally decreased in the left-sided lesioned PD rats, compared with normal control. Brain PET imaging studies in normal monkey showed that 18F-FP-β-CIT was concentrated in striatum. The test of undue toxicity showed that the dose received by mice was 1250 times as by human, which indicates that 18F-FP-β-CIT is very safe. So 18F-FP-β-CIT is a promising PET imaging agent for DAT with safety and validity.展开更多
目的 探讨西妥昔单抗联合5-氟尿嘧啶+顺铂(5-fluorouracil+cisplatin,FP)方案对中晚期食管癌患者肿瘤标志物及外周血磷脂酰肌醇-3激酶信号通路关键蛋白(phosphatidylinositol3 kinase,PI3K)、蛋白激酶B信号通路关键蛋白(phosphorylated ...目的 探讨西妥昔单抗联合5-氟尿嘧啶+顺铂(5-fluorouracil+cisplatin,FP)方案对中晚期食管癌患者肿瘤标志物及外周血磷脂酰肌醇-3激酶信号通路关键蛋白(phosphatidylinositol3 kinase,PI3K)、蛋白激酶B信号通路关键蛋白(phosphorylated protein kinase B,pAKT)、微小核糖核酸-21(microribonucleic acid-21,miR-21)表达水平的影响。方法 将中晚期食管癌患者80例作为研究对象,用随机数字表法分为A组和B组,每组40例。A组给予FP方案治疗,B组在A组治疗的基础上加用西妥昔单抗。3周为1个周期,连续治疗4个周期。比较2组治疗后的临床疗效,治疗前、后的生存质量、功能状态、碱性成纤维细胞生长因子(basic fibroblast growth factor,bFGF)、可溶性E-钙黏蛋白(soluble E-cadherin,sE-Cad)、肿瘤标志物、PI3K、pAKT及miR-21和治疗期间的安全性。结果 治疗4个周期后,2组的总有效率比较差异无统计学意义(P>0.05)。治疗后,2组欧洲癌症研究组织生存质量测定表(European Organization for Research and Treatment of Cancer Quality of Life Questionnair,EORTC QLQ-C30)和卡氏功能状态(Karnofsky performance status,KPS)评分均升高,且B组高于A组;血清bFGF、sE-Cad、鳞状细胞癌抗原(squamous cell carcinoma antige,SCC)、癌胚抗原(carcinoembryonic antigen,CEA)、糖类抗原125(carbohydrate antigen 125,CA125)、细胞角蛋白19片段抗原(cytokeratin 19 fragment antigen21-1,CYFRA21-1)、外周血PI3K、pAKT和miR-21水平均降低,且B组低于A组(P<0.05)。2组治疗期间不良反应发生率比较差异无统计学意义(P<0.05)。结论 西妥昔单抗联合FP方案可有效降低中晚期食管癌患者肿瘤标志物水平,调节相关因子水平,改善患者血管内皮功能,进而提高患者生存质量及功能状态,临床疗效和安全性良好。展开更多
Dopamine transporter (DAT) mediates the regulation of dopaminergic function. Two agents of TRODAT-1 and FP-CIT were observed in evaluating DAT change of Parkinson's disease (PD). The relationship between them was ...Dopamine transporter (DAT) mediates the regulation of dopaminergic function. Two agents of TRODAT-1 and FP-CIT were observed in evaluating DAT change of Parkinson's disease (PD). The relationship between them was also evaluated. The results suggested that 99mTc-TRODAT-1 SPECT and 131I-FP-CIT SPECT may serve as sensitive and objective in vivo markers to reflect the severity of PD. The 99mTc-TRODAT-1 image is more accurate and clearer compared with 131I-FP-CIT.展开更多
基金the National Natural Science Foundation (39770230) Natural Science Foundation ofJiangsu Province (BK99163) and Department of
文摘The ligand of N-(3-fluoropropyl)-2β-carbomethoxy-3β-(4’-iodophenyl) nortropane (FP-β-CIT) and mesylate precursor were synthesized by hydrolysis of cocaine, followed by dehydration, esterification, Grignard reaction, N-demethylation, iodination, N-alkylation with 3-bromopropanol and methylsulfonylation. Finally, 18F-FP-β-CIT was prepared by nucleophilic fluorination of the mesylate with K18F/K2.2.2 (Kryptofix). The labeling yield of 18F-FP-β-CIT is 25%~30%. The total radiochemical yield of this compound, calculated from the end of bombardment (EOB) with decay correction, is 10%~12% with a synthesis time of 100~110.min. The radiochemical purity of 18F-FP-β-CIT is greater than 90%, and this compound in aqueous solution is also stable for more than 4 hours at room temperature. It is stable enough for clinical study.
基金the National Natural Science Foundation of China (30570518)Science Foundation of Health Department of Jiangsu Province (H200401)
文摘The paper is to study pharmacologic characteristics of 18F-FP-β-CIT (18F-N-(3-fluoropropyl)-2β-carbomethoxy-3β- (4-iodophenyl)nortropane) as an imaging agent for dopamine transporter. The radiochemical purity of 18F-FP-β-CIT in aqueous solution was over 95% after standing at room temperature for 4h. Biodistribution displayed rapid uptake in rat brain (1.375 %ID/organ at 5min and 0.100 %ID/organ at 180 min) and the striatal uptake was 1.444, 0.731, 0.397, 0.230 and 0.146 %ID/g at 5, 30, 60, 120 and 180 min, respectively. The values of striatum/cerebellum, striatum /frontal cortex and striatum / hippocampus in rat's brain at 30 min were 3.38, 2.17 and 2.40 respectively. The uptake in striatum can be blocked by β-CFT, suggesting that 18F-FP-β-CIT binds to DAT peculiarly. The compound was rapidly cleared from monkey's blood. The striatal uptake was bilaterally decreased in the left-sided lesioned PD rats, compared with normal control. Brain PET imaging studies in normal monkey showed that 18F-FP-β-CIT was concentrated in striatum. The test of undue toxicity showed that the dose received by mice was 1250 times as by human, which indicates that 18F-FP-β-CIT is very safe. So 18F-FP-β-CIT is a promising PET imaging agent for DAT with safety and validity.
文摘目的 探讨西妥昔单抗联合5-氟尿嘧啶+顺铂(5-fluorouracil+cisplatin,FP)方案对中晚期食管癌患者肿瘤标志物及外周血磷脂酰肌醇-3激酶信号通路关键蛋白(phosphatidylinositol3 kinase,PI3K)、蛋白激酶B信号通路关键蛋白(phosphorylated protein kinase B,pAKT)、微小核糖核酸-21(microribonucleic acid-21,miR-21)表达水平的影响。方法 将中晚期食管癌患者80例作为研究对象,用随机数字表法分为A组和B组,每组40例。A组给予FP方案治疗,B组在A组治疗的基础上加用西妥昔单抗。3周为1个周期,连续治疗4个周期。比较2组治疗后的临床疗效,治疗前、后的生存质量、功能状态、碱性成纤维细胞生长因子(basic fibroblast growth factor,bFGF)、可溶性E-钙黏蛋白(soluble E-cadherin,sE-Cad)、肿瘤标志物、PI3K、pAKT及miR-21和治疗期间的安全性。结果 治疗4个周期后,2组的总有效率比较差异无统计学意义(P>0.05)。治疗后,2组欧洲癌症研究组织生存质量测定表(European Organization for Research and Treatment of Cancer Quality of Life Questionnair,EORTC QLQ-C30)和卡氏功能状态(Karnofsky performance status,KPS)评分均升高,且B组高于A组;血清bFGF、sE-Cad、鳞状细胞癌抗原(squamous cell carcinoma antige,SCC)、癌胚抗原(carcinoembryonic antigen,CEA)、糖类抗原125(carbohydrate antigen 125,CA125)、细胞角蛋白19片段抗原(cytokeratin 19 fragment antigen21-1,CYFRA21-1)、外周血PI3K、pAKT和miR-21水平均降低,且B组低于A组(P<0.05)。2组治疗期间不良反应发生率比较差异无统计学意义(P<0.05)。结论 西妥昔单抗联合FP方案可有效降低中晚期食管癌患者肿瘤标志物水平,调节相关因子水平,改善患者血管内皮功能,进而提高患者生存质量及功能状态,临床疗效和安全性良好。
基金National "Tenth Five" Scientific Technique Research Plan Project (2001BA702B02)
文摘Dopamine transporter (DAT) mediates the regulation of dopaminergic function. Two agents of TRODAT-1 and FP-CIT were observed in evaluating DAT change of Parkinson's disease (PD). The relationship between them was also evaluated. The results suggested that 99mTc-TRODAT-1 SPECT and 131I-FP-CIT SPECT may serve as sensitive and objective in vivo markers to reflect the severity of PD. The 99mTc-TRODAT-1 image is more accurate and clearer compared with 131I-FP-CIT.
