Preparation and Biological Evaluation of Novel 18F-labeled Phosphonuim Cation for Myocardial Perfusion Imaging with PET

In order to develop new PET myocardial perfusion imaging agent, a novel¹⁸F labeled phosphonium cation: (3-(［¹⁸F］fluoromethyl)benzyl) tris (2, 6-dimethoxyphenyl) phosphonium salt, ¹⁸F-2, had been designed and prepared. Biological evaluation of¹⁸F-2 had been performed in Kunming normal mice.¹⁸F-2 was obtained by a simple one-pot method and the radiochemical yield was (31±3)%. The total radio-synthesis time was less than 60 min and the radiochemical purity of final radiotracer was more than 95%. The biodistribution of¹⁸F-2 displayed a high heart uptake and good retention. The heart uptake of¹⁸F-2 at 5 and 60 min post-injection were (53.88±7.45)%ID/g and (23.93±3.28)%ID/g, respectively.¹⁸F-2 exhibited low radio-accumulation in non-target tissues and rapid clearance in liver, lung and blood. The heart to liver, heart to lungs and heart to blood ratio values were 3.99, 3.80 and 9.17, respectively. The results indicated that¹⁸F-2 could be as a promising myocardial perfusion imaging agent for PET imaging.     

多功能模块合成心肌显像剂18F-FTHA及Micro-PET显像

用国产氟多功能模块合成心肌脂肪酸代谢显像剂18F-FTHA用于临床研究.以苄基-14-（R,S）-对甲苯磺酰基-6-硫代十七烷酸酯为前体,在氟多功能模块上经亲核反应、水解及HPLC纯化,最后经固相萃取,得到18F-FTHA.研究其在正常NH小鼠体内的生物学分布以及正常SD大鼠Micro-PET显像.结果显示,18F-FTHA不校正合成效率为10.6％,合成时间为50min.18F-FTHA的放化纯度为99％,体外稳定性良好.生物学分布结果表明,60 min心肌摄取为19.04 ID％/g;心与肝放射性摄取比在60～90 min达到3～6倍;Micro-PET心肌显像清晰.结果提示,国产氟多功能模块合成18F-FTHA耗时短,放化纯度高,其质量符合氟-18药物的临床.     

18F-标记的前列腺特异性膜抗原JK-PSMA-7的制备及初步PET/CT显像

为合成一种新型¹⁸F^-标记的前列腺特异性膜抗原¹⁸F-JK-PSMA-7,经亲核取代、酸水解、高效液相色谱分离、固相萃取等4步合成¹⁸F-JK-PSMA-7,并测定其质量和体外稳定性,计算其脂水分配系数,通过动物实验评价其生物安全性和生物分布特性,同时对1例健康志愿者和3例前列腺癌患者行PET/CT显像。结果表明,¹⁸F-JK-PSMA-7的合成时间为45 min,合成产率为(31.0±2.5)%(未衰减校正,n=3),放化纯度>99%,体外稳定性良好,常温放置3个半衰期放化纯度仍>95%,脂水分配系数logP=-3.56±0.13,其他质控结果满足临床要求。生物分布实验显示其在体内稳定性较好,在所测时间点肌肉和骨骼几乎无摄取,药物在膀胱内的摄取较高,证明其经泌尿系统代谢。对1例健康志愿者和3例前列腺癌患者行PET/CT显像发现：1例健康志愿者主要在唾液腺、泪腺、下颌下腺、肝脏、脾脏和肠道、膀胱等器官有生理性高放射性摄取,3例前列腺癌患者前列腺病灶和转移灶都有浓聚,...     

Full Automated Synthesis of18F-FDOPA and Preliminary PET/CT Imaging

¹⁸F-fluoro-L-dihydroxyphenylalanine (¹⁸F-FDOPA) as a dopamine neurotransmitter imaging agent has been widely used for diagnosis and therapy evaluation of Parkinson's disease, brain tumors and neuroendocrine diseases with positron emission tomography (PET) imaging in clinical setting and research. To meet the increasing clinical demand in oncology and neurology, a routine protocol for the automated synthesis of¹⁸F-FDOPA with a disposable cassette system on an imported multifunctional synthesizer was studied and discussed.¹⁸F-FDOPA was automatically synthesized via a multiple-step reaction, including fluorination, reduction, iodization alkylation and hydrolysis, following purification by using a semi-preparative high-performance liquid chromatography (HPLC) system which was built in the multifunctional synthesizer. After HPLC purification, the purified¹⁸F-FDOPA solution was collected and passed through a sterilizing filter into a collection bottle. The final¹⁸F-FDOPA injection was obtained for quality control (QC) determination. The QC indexes of the final products were detected： the injection was colorless and transparent, pH value was at 4 to 5.5, radiochemical purity >98%, radionuclide purity >99%, specific activity >1.9 GBq/μmol, K_2.2.2 content <50 mg/L, methanol content <0.01%, alcohol content <0.01%, dichloromethane content <0.01 mg/L, dimethylformamide content <15 mg/L, bacterial endotoxin test <0.100 EU/mL, sterility test 0 cfu/mL,and abnormal toxicity test was negative. PET/CT imaging of rats was performed by intravenous injection of¹⁸F-FDOPA half an hour after the intraperitoneal injection of carbidopa, PET/CT scan was performed after 100 min post-injection. The imaging of¹⁸F-FDOPA showed symmetry high uptake in the bilateral striatum of normal rats. The decay-corrected radiochemical yield of¹⁸F-FDOPA from the¹⁸F-fluoride was (63.1±3.8)% (n=10) at the end of synthesis (EOS), the radiochemical purity was no less than 98%, and the total radiosynthesis time was within 80 min. The quality control results demonstrated that the quality indexes of the final injection solution met the relevant requirements of radiopharmaceutlcals, which were well-suited for clinical application. An efficient and high reproducible automatic method for the radiosynthesis of¹⁸F-FDOPA with high radiochemical yields and good radiochemical purity is obtained and performed via a multi-step reaction on the multifunctional synthesizer.¹⁸F-FDOPA can be used for animal and human PET imaging.     

Distribution of Dopamine D2 Receptor PET Imaging Agent 18F-Fallypride in the Brain of Normal and Aged Rats

With the progress of population aging, the incidence of age related disease has greatly increased. The dopamine D2 receptor is closely related to the age-related diseases, such as PD and AD. The PET imaging of the dopamine D2 receptor can provide noninvasive, dynamic, early and quantitative information on the function of the brain. So we intend to prepare dopamine D2 receptor PET imaging agent¹⁸F-Fallypride and to study the disturbution of the agent in the brain of normal and aged rats, further to explore the relationship between dopamine D2 receptor and senility.¹⁸F-Fallypride was prepared by nucleophilic reaction. And the PET image was performed in aged and normal rats 15 minutes after injection of the agent .Striatums were delineated as the region of interesting (ROI), the standard uptake value (SUV) of which was calculated. PMOD was used for image fusion ,partition and quantitative analysis of standard uptake values of each brain area. After imaging, cardiac ventricle was perfused. The brain was obtained and frozen. The contour structure was observed by HE staining.The results showed that the labeling yield was over 95% and the radiochemical purity was higher than 98%. The stability was still over 95% 2 hours after incubation with PBS. The striatum uptake of¹⁸F-Fallypride radioactivity in aged and normal rats 15 minutes after injection were (0.58±0.11)%ID/g, (0.39±0.14)%ID/g. The uptake of cortex cingulate, cortex insular, hypothalamus, olfactory, midbrain in normal rats ((0.120±0.012)%ID/g, (0.182±0.002)%ID/g, (0.111±0.002)%ID/g, (0.127±0.007)%ID/g, (0.083±0.012)%ID/g respectively) were inferior to aged rats ((0.154±0.013)%ID/g, （0.344±0.014）%ID/g, （0.244±0.019）%ID/g, （0.263±0.020）%ID/g, （0.216±0.012）%ID/g), which was displayed by PMOD. HE staining showed severe brain injury in elderly SD rats. Some neurons in the aged SD rats appeared acidophil change or nuclear fragmentation, accompanied by spongy deformation, lamellar or focal neuronal necrosis, and no obvious morphological changes. The relevance between dopamine D2 receptor and senility was demonstrated by PET imaging, which provided a basis for further research on the methodology of disease and pharmacodynamics research.     

Preparation and Clinical Application of 18F-DCFPyL

¹⁸F-DCFPyL, a PSMA-based PET imaging agent for prostate cancer, was auto synthesized and evaluated. Following the direct nucleophilic heteroaromatic substitution with ［¹⁸F］fluoride at the ortho-position of precursor, the deprotection of the ester moieties of the intermediate with different acids was attempted to obtain a good hydrolysis yield. The biodistribution in normal NIH mice and PET/CT imaging for a patient with biochemical recurrence of prostate cancer were also performed. The results showed that no remarkable discrepancy of the hydrolysis efficiency was found among three kinds of acids, H₃PO₄, HCl and HI, which were 17.1%, 16.9% and 18.4%, respectively with a specific activity of 54 to 90 GBq/μmol. The highest levels of radioactivity in the NIH mice were observed in the kidneys. Meanwhile, the uptake of the tracer in the blood was declined rapidly and a low accumulation of the radio-tracer was observed in most of the other organs. ¹⁸F-DCFPyL PET imaging for a postoperative patient with biochemical recurrence of prostate cancer can detect small metastatic foci that can not be detected by the CT. ¹⁸F-DCFPyL was synthesized reliably and repeatedly by domestic synthesis module and it passed the quality control. It has satisfactory properties in vivo and is probably suitable for early diagnosis of prostate cancer and detection of lesions in patients with biochemical recurrence of prostate cancer.     

Tau蛋白显像剂18F-THK5317的合成与初步临床应用

¹⁸F-THK5317是以tau为靶点的新型分子探针，本研究利用国产氟多功能模块自动化合成¹⁸F-THK5317，在动物实验基础上进行了初步的临床研究。以(S)-2-(4-甲氨基苯基)-6-［［2-(四氢吡喃基-)-3-对甲苯磺酰氧基］丙氧基］喹啉为前体，经亲核反应、酸水解、碱中和，分别采用混合液直接HPLC纯化与混合液经C18小柱预纯化后再HPLC分离纯化两种方法得到¹⁸F-THK5317；研究了药物在正常KM小鼠体内生物学分布；对比了¹⁸F-THK5317在正常人（HC）和阿尔茨海默病（AD）患者脑中PET/MR显像结果。先以C18小柱预纯化粗产品再用HPLC分离，能显著改善HPLC分离效果和提高产品放化纯度。¹⁸F-THK5317未校正合成产率为（18.7±5.3）%（n=7），放化纯度大于95%。小鼠生物分布表明，探针易穿透血脑屏障，并且能迅速从正常脑组织清除，Brain_{1 min}/Brain_{60 min}放射性摄取比为34；PET/MR结果显示，AD患者双侧颞叶、皮层的放射性滞留均高于健康对照。以上结果表明，国产氟多功能模块能够稳定高效地合成符合药物质控标准的¹⁸F-THK5317，动物实验及初步临床研究表明¹⁸F-THK5317具有在体显像tau蛋白的潜力。     

Preparation of 18F Labeled Octreotide Derivatives18F-Ta-Gluc-TOCA byClick Chemistry and its Biological Evaluation

The preparation of ¹⁸F labeled peptides usually needmany reaction steps, long time, harsh reaction conditions, which greatly limitsthe application of ¹⁸Flabeled PET probe. Using click chemistry for the synthesis of ¹⁸F labeled peptides make thereaction conditions more reliable, efficient and selective. The reactionconditions are mild, low cost, and fast. The purpose of this research was tosynthetize the glycosylated octreotide derivative quickly and easily, todevelop a method of ¹⁸Flabeled peptides by click chemistry. We also discussed the exploration of thefeasibility with ¹⁸Flabeled glycosylated octreotide derivatives as a somatostatin receptor positivetumor probe. This work prepared 2-¹⁸F-azide ethane precursor compounds by nucleophilic substitution and then labeledPr-Gluc-TOCA by click chemistry, finally we got the product ¹⁸F-Ta-Gluc-TOCA by purification.In addition, the in vitro stability and octanol water partition coefficient of ¹⁸F-Ta-Gluc-TOCA were measured.The biodistribution studies of ¹⁸F-Ta-Gluc-TOCAin normal mice and tumor bearing nude mice were investigated. The radiochemicalpurity of ¹⁸F-Ta-Gluc-TOCAwas 91%. The vitro stability was good. The octanol-water partition coefficientwas -0.43±0.05.The results of biodistribution in normal mice showed rapid clearance fromblood, and excreted mainly through the hepatobiliary metabolism, and also throughthe renal metabolism. The results of the biodistribution in tumor bearing nudemice showed high uptake in the tumor (4.34±0.47%ID/g, 60 min). The findings suggest that ¹⁸F-Ta-Gluc-TOCA is a potentialradiotracer for PET imaging of somatostatin receptor positive tumors.     

Aβ显像剂18F-AV45的自动化合成及临床验证

使用进口氟多功能合成模块TRACERlab FX2 N合成器自动化合成β-淀粉样蛋白（β-amyloid protein, Aβ）正电子显像剂¹⁸F-AV45,并进行临床验证。在TRACERlab FX2 N合成器上,以AV105为前体,与18F-发生亲核反应后,依次经酸水解及碱中和,经过高效液相色谱法（high performance liquid chromatography, HPLC）分离并纯化后获得¹⁸F-AV45,进行质量控制。并用制备的¹⁸F-AV45对1例阿尔兹海默病（Alzheimer disease, AD）患者及1例健康对照者行¹⁸F-AV45 PET/CT扫描。结果表明,¹⁸F-AV45合成时间为80 min,不校正合成效率为（17.02±1.52）%（n=6）,产品放化纯度大于95%。临床应用显示¹⁸F-AV45在AD患者大脑皮层摄取弥漫增高,提示大脑皮层β淀粉样蛋白沉积;在健康对照者大脑皮层未见明显摄取,即大脑皮层未见β淀粉样蛋白沉积。TRACERlab FX2 N合成器自动化合成¹⁸F-AV45简便快捷,重复性好,制备出的¹⁸F-AV45产品质量符合临床要求,该合成方法可为¹⁸F-AV45模块合成提供参考。     

5-羟色胺转运蛋白显像剂~(11)C-DASB的自动化合成及Micro PET/CT显像

目的:自动化合成5-羟色胺转运蛋白显像剂11 C-DASB并进行大鼠Micro PET/CT显像;方法:通过改变甲基化试剂、溶解前体溶剂及反应条件,得到优化的标记条件作为碳-11多功能合成模块的输入参数,进行自动化合成11 C-DASB,大鼠静脉注射11 C-DASB 45 min后进行显像;结果:采用11 C-CH3-Triflate作为甲基化试剂,通入新配制的含1mg去甲基DASB前体的500μL DMSO溶液内,80℃下加热2min,标准率为63.7%,大鼠显像表明,11 C-DASB特异性的浓聚于SERT富集区域;结论:经优化,11 C-DASB自动化合成可得到较高产率,大鼠显像表明,其特异性浓聚于SERT富集区域,有望作为5-羟色胺转运蛋白显像剂。     

(N-[~(18)F]氟甲基)-胆碱的自动化合成及其生物分布研究

采用住友CFN-multi-P100多功能模块快速、自动化合成(N-[~(18)F]氟甲基)-胆碱(~(18)F-FCH),并评价其在正常小鼠体内生物分布,以及胰腺癌裸鼠模型的PET/CT显像情况。前体CH2Br2与~(18)F-气相反应生成18FCH2Br,18FCH2Br经4个Si柱纯化后与三氟甲基磺酰银(Ag-Triflate)反应生成活性更高的氟代三氟甲基磺酰基甲烷(~(18)FCH2OTf),新中间体与预先加在C-18柱子上的N,N-二甲基乙醇胺(DMAE)反应再经SEP-PAK CM柱纯化得到18F-FCH。将~(18)F-FCH静脉给予正常小鼠,分别在给药后5、10、30、60、90、120min处死,测定主要脏器的质量及放射性计数。将~(18)F-FCH静脉给予胰腺癌裸鼠,注射10min后观察荷瘤裸鼠的PET/CT显像情况。结果显示,~(18)F-FCH合成时间32min,未校正的合成效率为(25±5)%(n=23),放化纯度大于97%。小鼠体内生物分布实验显示,18F-FCH在血液中清除快,绝大多数脏器在5min时放射性分布达最高值,后逐渐降低或处于相对稳定状态。放射性主要分布在肾脏、肝脏,而脑、肺、肌肉对~(18)F-FCH的摄取均较少。荷瘤(胰腺癌)裸鼠的PET/CT显像表明,~(18)FFCH在裸鼠肾脏、肝脏和脾脏聚集,胰腺癌细胞对~(18)F-FCH未见明显摄取。结果提示,住友CFN多功能模块可自动化、快速合成18F-FCH。18F-FCH在正常小鼠体内分布与文献报道的11 C-胆碱相似,具有一定的应用前景,但其对胰腺癌的诊断仍需进一步研究。     

~(99m)Tc-帕米膦酸盐的制备及骨分布

为观察99mTc标记的帕米膦酸盐(Pamidronate,PAM)的骨分布特点,以氯化亚锡为还原剂,优化99mTc直接标记PAM的条件,研究SnCl2(Ⅱ)含量、配体用量、pH及反应时间对标记率的影响,确定了优化的标记条件;考察99mTc-PAM的体外稳定性;评价99mTc-PAM在正常鼠体内的生物分布,尤其是骨摄取情况,比较99mTc-PAM与99mTc-MDP在正常小鼠体内的骨摄取。实验结果表明,PAM的99mTc标记方法简单,标记率大于95%,标记物体外稳定性好。正常鼠体内分布实验发现,99mTc-PAM骨摄取很高,且滞留时间长,在血液中清除快,在体内主要通过肾代谢;正常大鼠SPECT显像骨组织清晰可见,具有很好骨显像效果。与99mTc-MDP在正常小鼠体内的生物分布结果比较表明,99mTc-PAM的骨放射性摄取及骨与血放射性摄取比在不同时相均优于99mTc-MDP。研究表明,99mTc-PAM具有理想的骨显像性能,可用于骨显像、骨损伤探测以及肿瘤骨转移检测等应用研究。     

64Cu-NOTA-NOC的制备及体内生物分布初步研究

对生长抑素八肽类似物NOTA-NOC进行⁶⁴Cu标记,并对⁶⁴Cu-NOTA-NOC的体外稳定性、脂水分配系数、正常及荷瘤小鼠体内分布进行初步研究。建立⁶⁴Cu-NOTA-NOC的标记及质控条件;考察⁶⁴Cu-NOTA-NOC的体外稳定性,测定其脂水分配系数;通过尾静脉注射⁶⁴Cu-NOTA-NOC至小鼠体内,进行生物分布研究。结果表明：室温条件下即可获得标记率大于95%的⁶⁴Cu-NOTA-NOC;⁶⁴Cu-NOTA-NOC在缓冲溶液及10%胎牛血清溶液中具有良好的稳定性,脂水分配系数为-1.12±0.005 6;⁶⁴Cu-NOTA-NOC在正常昆明（KM）小鼠体内主要经肾脏代谢,血液摄取值随时间下降明显,显示其体内清除速度较快;在荷BON-1胰腺癌裸鼠体内也主要经肾脏代谢;在肿瘤中具有较高的摄取,注后2 h,肿瘤/肌肉摄取比值达10.38;荷BON-1胰腺癌裸鼠的PET/CT显像结果显示,1 h时,肿瘤对⁶⁴Cu-NOTA-NOC的摄取率最高,为7.7%ID/g,而给予阻断剂后,肿瘤对⁶⁴Cu-NOTA-NOC的摄取率显著降低,为0.94%ID/g。NOTA-NOC的⁶⁴Cu标记在室温条件下即可完成,⁶⁴Cu-NOTA-NOC在缓冲溶液及10%胎牛血清中具有较好的稳定性;其在动物体内主要经肾脏代谢,体内清除较快,在胰腺癌肿瘤组织中有较高摄取;PET/CT实验结果显示肿瘤对⁶⁴Cu-NOTA-NOC的摄取具有特异性。初步的研究结果表明,⁶⁴Cu-NOTA-NOC具有用于胰腺癌诊疗的潜质,值得开展进一步研究。     

新型Aβ斑块显像剂18F-W372

合成诊断阿尔茨海默病（Alzheimer’s disease,AD）的Aβ斑块显像剂：7-甲氧基-2(6-［¹⁸F］-氟-吡啶-3-基)咪唑［2,1-β］-8-吡啶噻唑（¹⁸F-W372）,不校正合成效率为（25.3±7.1）%（n=6）,产品放化纯大于99.5%,比活度为659~721PBq/mol。 ^{18F-W372小鼠体内分布实验显示,初始5min脑摄取为（4.36±1.44）%ID/g,清除较快,30min为（0.54±0.16）%ID/g,摄取比达到8,具有良好的生物学性能。急性毒性实验表明该药物安全可靠。在体试验显示药物注射40min,AD患者平均皮层/小脑吸收显著高于健康老年对照组。18F-W372是一种潜在的脑内Aβ淀粉显像剂。}     

68Ga标记成纤维细胞活化蛋白抑制剂的生物分布和胶质瘤模型micro-PET显像

为研究⁶⁸Ga标记的成纤维细胞活化蛋白抑制剂（⁶⁸Ga-FAPI-04）在正常小鼠和胶质瘤裸鼠模型体内的生物学分布及micro-PET显像,以DOTA修饰的成纤维活化蛋白抑制剂为前体合成⁶⁸Ga-FAPI-04。放射性HPLC测定其标记率,考察放化纯度及体外稳定性,通过测定⁶⁸Ga-FAPI-04脂水分配系数评估其水溶性。将20只ICR小鼠随机分为5组,尾静脉注射3.7 MBq ⁶⁸Ga-FAPI-04后5、15、30、60、120 min后处死并取出各脏器,称重并测定放射性计数,计算各组织器官的放射性摄取率。建立U87MG胶质瘤荷瘤鼠模型,进行生物分布及micro-PET显像研究。结果表明,⁶⁸Ga-FAPI-04的标记率为97.38%±1.32%（n=3）,放化纯度为100%,体外稳定性好,亲水性强。ICR正常小鼠生物分布实验显示,⁶⁸Ga-FAPI-04血液清除快,肾脏为主要排泄器官,脑部放射性摄取低。U87MG荷瘤裸鼠生物分布及micro-PET均显示肿瘤部位有较高的放射性摄取率,⁶⁸Ga-FAPI-04注射后90 min时肿瘤部位放射性摄取率达到（2.50±0.00）%ID/g。注射后30、60、90、120 min时,肿瘤与正常脑的肿瘤本底比(tumor-to-background ratio, TBR)分别为（6.26±0.09）、（5.06±0.02）、（5.54±1.47）、（5.51±0.03）。研究表明,⁶⁸Ga-FAPI-04制备简易方便、标记率高、体外稳定性好,主要通过肾脏排泄,在胶质肿瘤模型中具有较好的肿瘤靶向性,micro-PET显像清晰,是潜在的脑肿瘤显像剂。     

18F-NaF注射液的制备及新西兰兔骨折显像

由外伤或肿瘤骨转移造成的隐匿性骨折和愈合情况的准确诊断对制定合适的治疗方案具有非常重要的意义。为考查¹⁸F-NaF PET显像用于骨折诊断的诊断效能，本研究制备了¹⁸F-NaF注射液，并对其进行了质量控制和稳定性研究，然后建立新西兰兔骨折动物模型，模型建立约2周后进行了¹⁸F-NaF PET显像和⁹⁹Tc^m-亚甲基二磷酸盐（⁹⁹Tc^m-MDP）SPECT显像的自身对照实验，并对显像效果进行了比较。结果表明：¹⁸F-NaF的产量大于37 GBq，各项检验结果均符合质控要求，40 ℃下放置8 h和30 ℃下放置10 h所有检验结果均无明显变化；¹⁸F-NaF PET和⁹⁹Tc^m-MDP SPECT两种显像方式均可见全身骨骼，骨折部位呈明显放射性浓聚，但¹⁸F-NaF给药后30 min即可进行PET显像，骨折部位显示更为清晰，骨折部位与对侧正常骨骼的放射性摄取比（T/NT）明显高于⁹⁹Tc^m-MDP，而⁹⁹Tc^m-MDP需在给药后2 h才能进行SPECT显像。本研究表明¹⁸F-NaF PET对骨折的显像性能优于⁹⁹Tc^m-MDP，可明显提高检查流通量和诊断效能。     

超顺磁性氧化铁纳米粒子SPION-dopa-PEG-DOTA/RGD的~(64)Cu标记、纯化及生物分布

对64 Cu标记超顺磁性氧化铁纳米粒子SPION-dopa-PEG-DOTA/RGD的标记及纯化条件进行探索,并根据其在小鼠体内的生物分布研究结果,揭示其主要的代谢方式。通过对标记过程中配体浓度、温度、时间等条件的改变,探究64 Cu标记SPION-dopa-PEG-DOTA/RGD的最优条件;并采用二乙基三胺五乙酸(DTPA)螯合标记混合物中游离的64 Cu,经PD-10柱纯化后得到放化纯较高的标记物;采用快速薄层层析法测定标记物的标记率和放化纯;分别测定了标记物的体外稳定性和脂水分配系数;将64 Cu标记的氧化铁纳米粒子经尾静脉注射到正常鼠的体内,分别于注射后不同时间点取各脏器,称重、测定放射性计数率,计算每克组织的百分注射剂量率(%ID/g)。经条件优化后得到的64 Cu-SPION-dopa-PEG-DOTA/RGD的标记率为63%,PD-10柱纯化后放化纯大于95%,水溶性良好,且放化纯在标记后12h内在磷酸盐缓冲液和人血清白蛋白中表现出了较高的稳定性;动物体内生物分布实验显示,该标记物在小鼠体内主要经肝脏代谢,肾脏排泄,血液中放射性清除较快。该标记物可用于后续的PET/MRI双模态显像的研究。     

氟［18F］比他班自动化合成及初步临床应用

氟［¹⁸F］比他班（¹⁸F-florbetaben）是美国FDA于2014年批准上市的β-淀粉样蛋白显像剂,主要用于诊断阿尔茨海默病（AD）或其他认知障碍疾病。本研究使用改良后的国产氟多功能模块,建立¹⁸F-florbetaben自动化生产工艺,并针对其临床应用效果进行初步验证。结果显示,¹⁸F-florbetaben自动化合成耗时38 min,不校正合成效率为（45.0±2.3）%（n=6）,放化纯度大于95%,其临床PET显像效果理想。结果表明,国产氟多功能模块可实现¹⁸F-florbetaben的自动化生产,且工艺可靠,合成时间短。本文研究成果有助于推动该显像剂的国内临床使用。     

烟碱乙酰胆碱受体显像剂2-[~(18)F]-A-85380的合成及大鼠脑磷屏显像

通过18F标记前体Me3N+-Boc-A-85380·CF3SO-3,合成了烟碱乙酰胆碱受体显像剂2-[18 F]-A-85380,并探讨该显像剂在大鼠脑内的分布。采用取代法以Me3N+-Boc-A-85380·CF3SO-3为反应前体,在含氮芳香环的2位用18F进行标记,合成nAChRs显像剂2-[18F]-A-85380;以聚酰胺薄膜为支持介质、生理盐水为展开剂,测定标记物的标记率和放化纯度;SD大鼠4只尾静脉注射0.5mL(1.48MBq)2-[18F]-A-85380,分别在5、60、120、180min时用多聚甲醛灌流固定,取出大脑做冠状位切片,将切片与磷屏在专用暗盒内曝光30min,取出磷屏进行扫描显影。结果表明:2-[18 F]-A-85380的标记率达93%,其放化纯在标记后2、4、6h均大于90%。磷屏显像结果显示:注药后60min时磷屏所受辐射最强,所得图像光强度大于5min、120min和180min的;丘脑分布最多、皮质次之、小脑及脑干分布较少。     

Automatic Synthesis of 18F-6-F-L-DOPA and its Application in Clinical PET Imaging

¹⁸F-6-Fluoride-L-DOPA (¹⁸F-DOPA) has an important value in the imaging diagnosis of neuroendocrine tumors. In this study, we used homemade Fluoride-module to synthesis¹⁸F-DOPA and evaluate its clinical imaging.¹⁸F-DOPA was synthesized by direct nucleophilic reaction with 6-boric acid-dimethoxy-L-DOPA as precursor, Cu(OTf)₂(py)₄ as catalyst, and hydrolysis by hydriodic acid. Quality control and the in vitro stability were preformed. The¹⁸F-DOPA was confirmed PET imaging of neuroendocrine neoplasms and control. It took 60 minutes from ¹⁸F ions to ¹⁸F-DOPA, no corrected efficiency was （10.0±2.3）% (n=6), radiochemistry purity was over 99%. It could got 7.4 GBq of¹⁸F-DOPA once time. The trace of ascorbic acid or ethanol could prevent radiolysis of ¹⁸F-DOPA. The striatum was seen at¹⁸F DOPA imaging. The radioactivity were mainly extracted through kidney and urine. A positive lesion in pancreatic in patient with neuroendocrine tumor.¹⁸F-DOPA was synthesized by direct nucleophilic reaction with homemade Fluoride-module. It could got good repeatability and high quality for clinical used.