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
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
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.
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.
