6-[~(18)F]氟-L-多巴的合成

以硝基藜芦醛为原料,采用亲核取代合成法,利用手性相转移催化烷基化等多步反应制备了6-[^18F]氟-L-多巴（^18FDOPA）,并用手性流动相和反相C18柱的HPLC法测定对映纯度。结果表明,^18FDOPA总的合成时间少于120min,经衰减校正后总放化产额约为6.3%,对映纯度和放化纯度分别大于95%和99%。     

6-[~(18)F]氟-L-多巴的合成

以硝基藜芦醛为原料 ,采用亲核取代合成法 ,利用手性相转移催化烷基化等多步反应制备了6 [18F]氟 L 多巴 (18FDOPA) ,并用手性流动相和反相C18柱的HPLC法测定对映纯度。结果表明 ,18FDOPA总的合成时间少于 12 0min ,经衰减校正后总放化产额约为 6 3% ,对映纯度和放化纯度分别大于 95 %和 99%     

6—[^18F]氟—L—多巴的合成与制备技术进展

介绍了合成6－[^18F]氟－L－多巴的意义和制约因素，亲电取代法和亲核取代法的主要原理、考虑因素和一些具有代表性的合成路线，并对这两类方法进行了比较。     

O-(2-~(18)F-氟代乙基)-L-酪氨酸的全自动合成

采用PET trace回旋加速器－FDG全自动合成系统，通过^18O(p,n)^18F核反应生产^18F^-，然后与乙二醇二对甲苯磺酸酯发生亲核氟化取代反应，生成2-^18F-氟代乙醇对甲苯磺酸酯，后者与L－酪氨酸二钠反应生成O－（2-^18F-氟代乙基）－L－酪氨酸（^18F-FET)。总合成时间为52min，未校正放化产率约为4％，放化纯度大于95％。     

99Tcm-HEDTMP的制备及其生物分布

采用SnCl2还原法制备了^99Tc^m－HEDTMP，研究了标记物的体外稳定性、兔SPECT骨扫描及小鼠体内分布。结果表明，^99Tc^m－HEDTMP具有较高的体外稳定性，5h内放化纯度＞95％；兔骨骼系统显像清晰；小鼠体内分布结果表明标记物主要被小鼠骨骼摄取，其它非目标组织的摄取较低、骨清除较快。这表明^99Tc^m－HEDTMP是非常有希望的新型骨显像剂。     

由大鼠体内分布估算6-18F-L-多巴在人体内的吸收剂量

在大鼠尾静脉注射6－^18F-L-多巴（^18F-DOPA）后5、30、60、90、120和150min时处死动物,测定大鼠体内各脏器中^18F活度分布,换算至标准人体内分布,按MIRD法估算人体^18F-DOPA内照射吸收剂量。估算结果表明,肾脏的内照射吸收剂量最高,为22.9pGy/Bq,脑的内照射吸收剂量为11.8pGy/Bq,其它脏器的内照射吸收剂量为（9－18）pGy/Bq,有铲剂量当量为20.5pSv/Bq。这表明,由大鼠体内分布资料可估算^18F-DOPA在人体内的吸收剂量,为临床安全应用^18F-DOPA提供了参考资料。     

18F标记氟甲基胆碱的半自动合成及其生物分布

利用^18F—FDG化学合成模块（CPCU）改装的半自动化多用氟标药物仪合成了氟甲基胆碱（^18F—FCH）,并进行了放射化学纯度测定、稳定性分析、生物分布、荷瘤小鼠显像以及安全性检验。利用半自动装置合成只需要55min,产率稳定,产品的放射化学纯度大于99％,体外稳定性良好。^18F-FCH的正常小鼠体内分布与文献报道的^11-CCholine相似,毒性较小。荷瘤小鼠显像结果表明,^18F—FCH可选择性地浓集于肿瘤细胞,是较好的肿瘤显像剂。     

肿瘤受体显像剂99Tcm-octreotide的放化纯度分析

采用高压液相色谱分析(HPLC)和双层析结合银染色两种方法，对新型肿瘤受体显像剂^99Tc^m—oc—treotide的放化纯度进行分析。结果表明，双层析法结合银染色可以准确、有效地分离^99Tc^m—octreotide及其它放射性组分，可以较精确地计算出显像剂的放化纯度。为Octreotide及其它多肤类显像剂的放化纯度测定提供了一种简捷、准确的新手段。     

~(18)F-6-L-多巴自动化合成及其初步PET/CT显像

~(18)F-6-L-多巴(~(18)F-FDOPA)作为多巴胺神经递质显像剂,已广泛应用于帕金森病、脑肿瘤以及神经内分泌疾病正电子发射断层(PET)显像诊断和疗效评估。本文使用进口多功能合成仪及其配套卡套和试剂盒,经氟化、还原、碘化、烷基化和水解多步反应,以及HPLC分离纯化,再经无菌过滤器传入产品瓶,得到~(18)F-FDOPA注射液,实现~(18)F-FDOPA自动化生产。并对获得的~(18)F-FDOPA注射液进行质量检测与分析:~(18)F-FDOPA注射液无色、澄清,pH为4~5.5,放化纯度98%,放射性核纯度99%,比活度1.9 GBq/μmol,K2.2.2含量50 mg/L,甲醇含量0.01%,乙醇含量0.01%,二氯甲烷含量0.01mg/L,二甲基甲酰胺含量15 mg/L,细菌菌内毒素0.100 EU/mL,无菌检查结果为0cfu/mL,异常毒性实验为阴性。正常Wistar大鼠腹腔注射卡比多巴30 min后,尾静脉注射~(18)FFDOPA,100min后行microPET/CT扫描,图像显示双侧纹状体可见对称性放射性摄取。进口多功能合成仪可高效、稳定地自动化合成~(18)F-FDOPA,合成时间约80min,校正放化产率为(63.1±3.8)%(n=10),放化纯度大于98%,产品质量达到动物和人体PET显像要求。     

中枢神经系统5—羟色胺受体显像剂WAY类似物的研究进展

阐述了WAY类似物在中枢神经系统5－羟色胺（5－HT）受体显像剂方面的研究状况,介绍了这类化合物在中枢神经系统5－HT受体显像剂方面的优越性,并对^99Tc^m标记WAY类似物受体显像剂的研究方法和进展进行了详细的阐述。     

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。     

PET显像剂~(18)F-氟化钠的制备、作用机制和临床应用

~(18)F-氟化钠是一种正电子发射计算机断层显像(PET)药物,主要用于成骨性反应活跃的骨疾病、尤其是恶性肿瘤骨转移的诊断。~(18)F-氟化钠PET骨显像具有高灵敏度和高特异性的特点,能更早发现99 Tcm-亚甲基二膦酸盐(99 Tcm-MDP)单光子发射计算机断层显像(SPECT)不能探测到的病灶。这对肿瘤治疗方案的选择和预后判断具有重要的临床意义。另外,18 F-氟化钠也能够有效鉴别破裂高风险的冠状动脉粥样硬化斑块。本工作就PET显像剂~(18)F-氟化钠的制备、质量控制、药理作用、辐射安全和临床应用作出综述。     

18F-FDG的放射性标记、显像原理与临床研究进展

PET/CT是当今最先进的诊断技术之一,实现了解剖学影像与功能学影像的融合。¹⁸F-FDG是最为重要的正电子药物,其使用量占全部PET/CT显像的95%以上。FDG-PET已经广泛应用于诊断肿瘤、心脏病和癫痫等多种疾病。本文回顾了¹⁸F-FDG的发展历史,介绍了¹⁸F-FDG的制备与质量控制,分析了¹⁸F-FDG显像原理,阐述了FDG-PET等临床应用研究进展。     

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.     

PET imaging of cerebral metabolic change in tinnitus using 18F-FDG

1 INTRODUCTIONTiunitus is a hearing disorder diaracterized by periodic or continuous auditory hallucination in one or both ear without real son-nd source. Over 90% of tin-"itus are associated with cochlear dysfUnction such as hearing loss. The sensory disorder varies inseventy. In the worst case j it induces unbearable noise in ear(s), even interfering withsleep and daily life. However, tinnitus is also a kind of "subjective" abnormality, becauseno morphological or fUllctional alteration…     

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.     

基于国产氟多功能合成模块的~(18)F-FMISO自动合成工艺验证

为验证特异性肿瘤PET乏氧显像剂1-H-1-(3-~(18)F-2-羟基丙基)-2-硝基咪唑(~(18)F-FMISO)注射液的临床前即时标记工艺的可行性、可靠性和稳定性,采用国产氟多功能自动化合成装置,以1-(2′-硝基-1′-咪唑基)-2-O-四氢吡喃基-3-O-甲苯磺酰基丙二醇(NITTP)为前体,经氟化、水解反应制备18 F-FMISO注射液,按照优化的制备工艺进行~(18)F-FMISO三批连续生产,并对其关键工艺参数和产品质量标准进行验证。结果表明:总合成时间小于40min,产品放化产率大于45%(未衰减校正,n=5),比活度大于3.7×1010 Bq/mmol,放置3个半衰期后放化纯度仍大于95%,体外稳定性良好。该自动合成工艺稳定可行,三批产品各项指标均符合质量标准规定,满足临床PET显像要求。     

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,...     

O-(2-[18F]氟乙基)-5-羟基-L-色氨酸(5-18FEHTP)的合成动物体内分布及MicroPET显像

通过对现有CTI公司计算机控制的化学合成模块(CPCU) 进行改造,首次合成了L-5-羟基色氨酸类似物(5-18FEHTP),并用高效液相(HPLC) 检测其放化纯度,所得的产品用于昆明小鼠的S180肉瘤模型显像。结果显示,采用改进方法合成5-18FEHTP的总时间是45min,纯化时间是20min,放化收率为12-16%(n=15),产品的放化纯度大于98%。MicroPET显像结果表明,5-18FEHTP在S180肉瘤浓集程度明显高于周围其它组织。以上结果提示利用CPCU半自动合成5-18FEHTP,方法简便、稳定、产品纯度较高。动物生物分布和显像结果表明5-18FEHTP可能成为一种新的PET显像剂。