18F-labeled FECNT: a selective radioligand for PET imaging of brain dopamine transporters

Fluorine-18 labeled 2beta-carbomethoxy-3beta-(4-chlorophenyl)-8-(2-fluoroethyl)nort ropane (FECNT) was synthesized in the development of a dopamine transporter (DAT) imaging ligand for positron emission tomography (PET). The methods of radiolabeling and ligand synthesis of FECNT, and the results of the in vitro characterization and in vivo tissue distribution in rats and in vivo PET imaging in rhesus monkeys of [18F]FECNT are described. Fluorine-18 was introduced into 2beta-carbomethoxy-3beta-(4-chlorophenyl)-8-(2-fluoroethyl)nort ropane (4) by preparation of 1-[18F]fluoro-2-tosyloxyethane (2) followed by alkylation of 2beta-carbomethoxy-3beta-(4-chlorophenyl)nortropane (3) in 21% radiochemical yield (decay corrected to end of bombardment [EOB]). Competition binding in cells stably expressing the transfected human DAT serotonin transporter (SERT) and norepinephrine transporter (NET) labeled by [3H]WIN 35428, [3H]citalopram, and [3H]nisoxetine, respectively, indicated the following order of DAT affinity: GBR 12909 > CIT > 2beta-carbomethoxy-3beta-(4-chlorophenyl)-8-(3-fluoropropyl) nortropane (FPCT) > FECNT. The affinity of FECNT for SERT and NET was 25- and 156-fold lower, respectively, than for DAT. Blocking studies were performed in rats with a series of transporter-specific agents and demonstrated that the brain uptake of [18F]FECNT was selective and specific for DAT-rich regions. PET brain imaging studies in monkeys demonstrated high [18F]FECNT uptake in the caudate and putamen that resulted in caudate-to-cerebellum and putamen-to-cerebellum ratios of 10.5 at 60 min. [18F]FECNT uptake in the caudate/putamen peaked in less than 75 min and exhibited higher caudate- and putamen-to-cerebellum ratios at transient equilibrium than reported for 11C-WIN 35,428, [11C]CIT/RTI-55, or [18F]beta-CIT-FP. Analysis of monkey arterial plasma samples using high performance liquid chromatography determined that there was no detectable formation of lipophilic radiolabeled metabolites capable of entering the brain. In equilibrium displacement experiments with CIT in rhesus monkeys, radioactivity in the putamen was displaced with an average half-time of 10.2 min. These results indicate that [18F]FECNT is a radioligand that is superior to 11C-WIN 35,428, [11C]CIT/RTI-55, [18F]beta-CIT-FP, and [18F]FPCT for mapping brain DAT in humans using PET.     

Biodistribution and catabolism of 18F-labeled N-epsilon-fructoselysine as a model of Amadori products

Amadori products are formed in the early stage of the so-called Maillard reaction between reducing sugars and amino acids or proteins. Such nonenzymatic glycosylation may occur during the heating or storage of foods, but also under physiological conditions. N-epsilon-fructoselysine is formed via this reaction between the epsilon-amino group of peptide-bound lysine and glucose. Despite the fact that, in certain heated foods, up to 50% of lysyl moieties may be modified to such lysine derivatives, up to now, very little is known about the metabolic fate of alimentary administered Amadori compounds. In the present study, N-succinimidyl-4-[18F]fluorobenzoate was used to modify N-epsilon-fructoselysine at the alpha-amino group of the lysyl moiety. The in vitro stability of the resulting 4-[18F]fluorobenzoylated derivative was tested in different tissue homogenates. Furthermore, the 4-[18F]fluorobenzoylated N-epsilon-fructoselysine was used in positron emission tomography studies, as well as in studies concerning biodistribution and catabolism. The results show that the 4-[18F]fluorobenzoylated N-epsilon-fructoselysine is phosphorylated in vitro, as well as in vivo. This phosphorylation is caused by fructosamine 3-kinases and occurs in vivo, particularly in the kidneys. Despite the action of these enzymes, it was shown that a large part of the intravenously applied radiolabeled N-epsilon-fructoselysine was excreted nearly unchanged in the urine. Therefore, it was concluded that the predominant part of peptide-bound lysine that was fructosylated during food processing is not available for nutrition.     

An improved synthesis of dopamine D2/D3 receptor radioligands [11C]fallypride and [18F]fallypride

Improved syntheses of dopamine D₂/D₃ receptor radioligands [¹¹C]Fallypride and [¹⁸F]Fallypride are reported. The phenolic precursor (9) for C-11 labeling and the Fallypride (10) reference standard were synthesized from the starting material 2-hydroxy-3-methoxy-5-(2-propenyl)benzoic acid methyl ester (1) in 7 and 8 steps with 16% and 5% overall chemical yields, respectively. The tosylated precursor (15) for F-18 labeling was synthesized from compound 1 in 5 steps with 32% overall chemical yield. An alternate synthetic approach for Fallypride has been developed using the same starting material 1 in 5 steps with 26% overall chemical yield. [¹¹C]Fallypride ([¹¹C]10) was prepared by O-[¹¹C]methylation of the phenolic precursor with [¹¹C]methyl triflate and purified with a semi-preparative HPLC method in 50–60% radiochemical yield, decay corrected to end of bombardment (EOB), based on [¹¹C]CO₂, and 370±185 GBq/μmol specific radioactivity at EOB. [¹⁸F]Fallypride ([¹⁸F]10) was prepared by nucleophilic substitution of the tosylated precursor with K[¹⁸F]F/Kryptofix 2.2.2 and HPLC combined with solid-phase extraction (SPE) purification in variable (up to 50%) decay corrected radiochemical yield from K[¹⁸F]F and 111–222 GBq/μmol specific activity at EOB.     

Biodistribution of [18F] SR144385 and [18F] SR147963: selective radioligands for positron emission tomographic studies of brain cannabinoid receptors

ABSTRACT. [¹⁸F] SR144385 and [¹⁸F] SR147963 were synthesized in a multistep reaction in which fluorine-18 was introduced by nucleophilic halogen displacement on a bromo precursor. The fluorine-18-labeled intermediate was deprotected and coupled with the appropriate alkyl amine to give the final products. Both radioligands had appropriate regional brain distribution for cannabinoid receptors with a target to nontarget ratio of 1.7 for [¹⁸F] SR147963 and 2.5 for [¹⁸F] SR144385 at 60 and 90 min postinjection, respectively. The uptake of both tracers was blocked with a 1 mg/kg dose of SR141716A.     

Effects of dopamine on the in vivo binding of dopamine D2 receptor radioligands in rat striatum

The effects of moderate changes in extracellular dopamine concentrations on the in vivo binding of specific dopaminergic D2 radioligands with different affinities and kinetics were investigated in rats. Either [125I]NCQ298 (Kd = 19 pM), or [25I]iodolisuride (Kd = 0.27 nM) or [3H]raclopride (Kd = 1.5 nM) were administered intravenously (IV) to animals 1 h after the intraperitoneal (IP) injection of either alpha-methyl-p-tyrosine (AMPT) (250 mg/kg) or nomifensine (15 mg/kg), or saline. The kinetics of radioactivity concentration in the striatum, cerebellum, and plasma were measured for up to 4 h after [125I]NCQ298 or [125I]iodolisuride injection and up to 1.5 h after [3H]raclopride injection. For each tracer, the striatum-to-cerebellum radioactivity concentration ratios (S/C) and the binding potential (BP), calculated as the association to dissociation binding rate constant ratios (k3/k4), were assessed and related to the changes in extracellular dopamine concentration induced by drug treatments. Results show that S/C and BP of [3H]raclopride were significantly diminished by pretreatment with nomifensine, a drug that increases extracellular dopamine concentration. Nomifensine pretreatment induced no changes in the in vivo binding indexes of the high affinity [125I]NCQ298 and a slight but not significant decrease of the binding indexes of 125I]iodolisuride. Treatment with AMPT, which induced a 40% reduction in dopamine concentration, did not change [125I]NCQ298 binding indexes but slightly increased those of [3H]raclopride and [125I]iodolisuride. In conclusion, the change of dopamine concentration induces modification of radiotracer kinetics. Thus, the combined use of tracers with high and low affinities could allow us to obtain information both on receptor density and neurotransmitter release in vivo. However, as indicated by the [3H]raclopride study with AMPT, small changes in the concentration of intrasynaptic dopamine cannot be easily detected.     

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.     

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.     

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.     

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

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.     

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.     

Biodistribution and first clinical results of 18F-SiFAlin-TATE PET: a novel 18F-labeled somatostatin analog for imaging of neuroendocrine tumors

European Journal of Nuclear Medicine and Molecular Imaging - PET/CT using 68Ga-labeled somatostatin analogs (SSA) targeting somatostatin receptors (SSR) on the cell surface of well-differentiated...     

18F-fallpride:一种多巴胺D2受体PET显像剂

18F-fallypride是一种新的多巴胺D2受体PET显像剂,它与多巴胺D2受体亲和力高(Ki=0.03nmol/L)、亲脂性适宜(logKw=2.43),适于纹状体及纹状体外多巴胺D2/D3受体显像.对其合成、药理作用及体内过程、临床应用等进行了综述.     

High affinity dopamine D2 receptor radioligands. 1. Regional rat brain distribution of iodinated benzamides.

Five 125I-labeled substituted benzamides, which are close structural analogues of (S)-sulpiride, eticlopride, and isoremoxipride, were evaluated for their selective in vivo uptake into dopamine D2 receptor rich tissue of the rat brain. "Iodopride" (KD 0.88 nM), an iodine substituted benzamide structurally related to sulpiride, displayed a maximal striatum: cerebellar uptake ratio of 7.6. Demonstration of saturation of the receptor with [125I]iodopride in striatum required uptake in frontal cortex to be used, rather than cerebellar uptake, to define nonspecific binding. Two other ligands structurally related to eticlopride, "iclopride" (KD 0.23 nM) and "itopride" (KD 0.16 nM), displayed maximal striatal: cerebellar uptake ratios of 9.8 and 3.3, respectively. The most potent ligands, "epidepride" (KD 0.057 nM) and "ioxipride" (KD 0.070 nM) showed striatal:cerebellar uptake ratios of 234 and 65, respectively. The observed uptake ratios correlated poorly with the affinity constants for the dopamine D2 receptor alone, but were highly correlated (r = 0.92) with the product of the receptor dissociation constant (KD) and the apparent lipophilicity (kw), as determined by reverse-phase HPLC at pH 7.5. Total striatal uptake also appeared dependent on lipophilicity, with maximal uptake occurring for ligands having log kw 2.4-2.8.