肿瘤PET分子探针3-O-(2-18F-氟乙基)-L-多巴的合成及初步生物学评价

正电子类氨基酸显像剂是¹⁸F-氟代脱氧葡萄糖（¹⁸F-Fluorodeoxyglucose,¹⁸F-FDG）在临床肿瘤PET显像应用中的重要补充。针对6-¹⁸F-氟-L-多巴（¹⁸F-FDOPA）前体制备及标记过程的复杂性,本研究设计合成了一种新型¹⁸F-标记的氨基酸类肿瘤PET显像剂3-O-(2-¹⁸F-氟乙基)-L-多巴（3-O-(2-¹⁸F-fluoroethyl-L-DOPA,¹⁸F-FEDOPA）,并对其内生物分布及肿瘤PET显像进行了评价。以L-多巴（L-DOPA）为原料经多步反应合成标记前体化合物-N-叔丁氧羰基-(3-O-甲苯磺酸酯乙基-4-O-叔丁氧羰基)-L-多巴甲酯,通过¹⁸F-亲核取代反应实现放射性标记,经半制备高效液相色谱纯化、盐酸水解、NaOH中和后得到¹⁸F-FEDOPA注射液。放化合成时间为90 min,放化产率（33±6）%（n=10,衰减校正）,放射性比活度为55 GBq/μmol,放化纯度>99％,4 h后测定放化纯度>95%,稳定性良好。小鼠体内生物分布表明,¹⁸F-FEDOPA主要经肾脏代谢,心脏和脑组织摄取值较低,骨骼摄取随时间无明显变化。microPET/CT显像显示,¹⁸F-FEDOPA在H22和S180肿瘤组织有明显摄取;与¹⁸F-FDG相比,¹⁸F-FEDOPA在注射60 min时肿瘤与心（或脑）的比值高。因此,¹⁸F-FEDOPA有望成为一种新型氨基酸代谢类肿瘤PET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。     

99mTc标记的前列腺特异性膜抗原抑制剂HYNIC-P137的制备与临床转化

为开发低膀胱滞留的前列腺癌SPECT显像剂，在⁶⁸Ga-P137结构的基础上制备了^99mTc-P137,对其进行临床前评估和初步的临床转化研究。通过固相合成方法制备标记前体HYNIC-P137,用EDDA作为共配体对前体进行^99mTc标记，并对产物^99mTc-P137进行质控。考察^99mTc-P137的脂水分配系数和体外稳定性，考察其在PSMA阳性细胞和阴性细胞上的摄取和抑制。进行正常昆明小鼠的生物分布和荷瘤鼠的SPECT/CT显像，最后进行临床转化研究。结果表明，前体HYNIC-P137的固相合成方便易得，标记产物^99mTc-P137的放化纯度接近100%,体外稳定性好，亲水性较强。正常昆明小鼠生物分布显示，该探针血液清除较快，主要通过肾脏代谢。荷瘤鼠的小动物SPECT/CT显示，^99mTc-P137主要在PSMA阳性肿瘤和肾脏区域浓集，且均可被明显抑制，显示出高度的体内特异性。临床转化显示，^99mTc-P13...     

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。     

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。     

~(18)F标记的白藜芦醇衍生物的合成及作为β-淀粉样斑块显像剂的初步评价

设计并合成四种白藜芦醇衍生物,以评价其用于Aβ-斑块PET显像的可能性。通过化学合成得到四种白藜芦醇衍生物的前体化合物和参比化合物;使用参比化合物测定其与Aβ1-42蛋白聚集体的体外结合性;经[~(18)F]亲核取代反应对具有较高亲和力的化合物进行放化标记,并进行体外稳定性、脂水分配系数、生物分布等的测定。体外竞争结合实验显示化合物(E)-1-(3,5-二甲氧基苯乙烯基)-4-(2-(2-(2-氟乙氧基)乙氧基)乙氧基)苯([~(19)F]F-7)具有中度的结合性(Ki=43.76nmol/L);[~(18)F]F-7的标记时间为32min,放化产率(未校正)为(23±2)%,经SEP PAK C18柱纯化后放化纯度大于95%,且在生理盐水中的稳定性大于3h,具有较好的脂溶性(lg P=3.08);生物分布实验显示化合物[~(18)F]F-7具有较快的脑清除,注射后2min和60min的脑摄取分别为(0.55±0.05)%ID/g和(0.06±0.01)%ID/g,清除比达到9。化合物[~(18)F]F-7是一种潜在的β-淀粉样斑块PET显像剂。     

O-（2-[^18F]氟代乙基）-5-羟基-L-色氨酸的合成、生物分布及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,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,放化收率为12％～16％（n=15）,产品的放化纯度〉98％。正常昆明小鼠体内生物分布显示,其脑组织摄取较低,最大摄取率为（2．354±0．405）％ID／g。血液清除较快,30min时摄取率已降为（2．974±0．278）％ID／g。肾脏给药60min摄取率值最大为（11．706±0．374）％ID／g,5-^18FEHTP经过肾脏排出体外。MicroPET小鼠显像结果表明,5-^18FEHTP在S180肉瘤中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。小鼠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。     

18F-FDG的稳定性及提高稳定性的方法

本工作研究了常规制备的大剂量、高浓度¹⁸F-FDG的稳定性,并在产品中添加稳定剂乙醇或对已部分分解的产品进行再纯化,以提高¹⁸F-FDG的放化纯度。结果显示,当¹⁸F-FDG产品浓度高于6 TBq/L时,放置4 h,其放化纯度＜95%;浓度大于7.4 TBq/L时,添加体积分数为0.1%的乙醇后,能明显降低¹⁸F-FDG的分解,6 h后放化纯度＞95%;已分解的¹⁸F-FDG经再纯化后,放化纯度＞99%。Micro PET/CT大鼠显像表明,采用已分解的¹⁸F-FDG对大鼠进行显像,其股骨有明显摄取;对其进行再纯化处理后对大鼠显像,大鼠股骨无放射性摄取。以上结果表明,高浓度的¹⁸F-FDG有效时间小于4 h;添加0.1%乙醇可明显减慢高浓度¹⁸F-FDG分解,而再纯化方法可以彻底除去分解的放射性杂质。为保证¹⁸F-FDG质量,将添加稳定剂和再纯化两种方法联合使用,保证产品放化纯度的同时还可提高¹⁸F-FDG的利用率。     

基于64Cu和超顺磁性氧化铁纳米粒子的PET/MRI双模态淋巴显像探针的研究

采用共沉淀法先合成了由葡聚糖包覆的超顺磁氧化铁纳米粒子（IO-Dex）,再用⁶⁴Cu标记二硫代氨基甲酸二磷酸盐(DTCBP),获得了⁶⁴Cu(DTCBP)₂。然后,利用DTCBP中二磷酸基团与氧化铁牢固结合的特点,将预标记的⁶⁴Cu(DTCBP)₂与IO-Dex结合,制备出一种用于淋巴结显像的PET/MRI双模态影像探针⁶⁴Cu(DTCBP)₂-IO-Dex。经分离纯化,⁶⁴Cu(DTCBP)₂-IO-Dex的放化纯度大于99%。该影像探针在Balb/C小鼠体内的生物分布结果显示：⁶⁴Cu(DTCBP)₂-IO-Dex 1 h时在腘窝淋巴结（PLN）和髂淋巴结（ILN）的吸收较高,分别为2.31%ID和1.84%ID;肝脏摄取最高,达15.41%ID/g;脾脏在3 h前无摄取。在PET/CT和MRI模式下,均能清晰地观察到腘窝淋巴结的摄取。     

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。     

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.     

国产FDG模块半自动合成~(18)F-氟乙基胆碱

18F-氟乙基胆碱(18F-FECH)是18F-FDG的重要补充,在脑瘤转移和前列腺癌及转移的诊断方面有重要的应用价值。利用国产单次PET-FDG-TI-I CPCU型FDG合成模块,未改变硬件,通过更改试剂与耗材,半自动合成18F-FECH,并在产品收集瓶前增加C18纯化柱,减少K2.2.2杂质的含量。合成时间约30min,放化产率42.0%(未时间校正,n=5),放置6h后放化纯度99.0%,体外稳定性良好;合成时间和产率与国内外模块结果相近。结果表明,在国产单次PET-FDG-TI-I CPCU型FDG模块上可半自动合成18F-FECH,合成效率及放化纯度较高。     

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.     

靶向前列腺特异膜抗原的放射性诊断药物的研究现状和进展北大核心CSCD

前列腺癌是男性常见的恶性肿瘤之一,较高的发病率和死亡率使其成为男性健康的重大威胁。目前,前列腺癌的常见诊断方法无法对前列腺癌进行早期、准确的诊断,而正电子发射断层显像/计算机断层成像(PET/CT)及单光子发射计算机断层成像/计算机断层成像(SPECT/CT)可对前列腺癌的发生和发展进行有效地早期诊断。前列腺特异性膜抗原(prostate-specific membrane antigen,PSMA)在前列腺癌细胞表面高表达,是前列腺癌显像和治疗的较理想靶点。本文首先简介了前列腺癌的发病情况及现行常见的诊断方法,然后描述了PSMA的基本结构及与单克隆抗体和小分子抑制剂的作用机理,接着,重点叙述了基于PSMA的放射性诊断药物(主要是^(99)Tc^(m)、^(68)Ga和^(18)F标记的药物)的研究现状和进展,最后,还对PSMA放射性诊断药物的前景进行了展望。     

64Cu标记DKFZ-PSMA-617探针的制备、质控及体内分布的研究

目的：利用医用回旋加速器固体靶系统制备PET核素⁶⁴Cu,进行前列腺特异性膜抗原（PSMA）分子探针DKFZ-PSMA-617（PSMA-617）研究。建立⁶⁴Cu-PSMA-617标记化合物生产及初步快速质量控制方法,为PSMA高表达肿瘤的PET显像及放射性免疫导向手术提供新型探针。方法：通过优化反应条件,实现固体靶制备的⁶⁴Cu对PSMA-617的快速标记与纯化。利用放射性薄层层析分析(Radio-thin layer chromatography, Radio-TLC)和放射性高效液相色谱(Radio-high performance liquid chromatography, Radio-HPLC),进行⁶⁴Cu-PSMA-617放化纯和稳定性检测。参考2015年《中国药典》进行⁶⁴Cu-PSMA-617的初步质量控制。通过静脉注射1.85 MBq的⁶⁴Cu-PSMA-617至Balb/c小鼠体内,进行该探针的体内分布研究。结果：⁶⁴Cu-PSMA-617的标记率>96%, 放化纯度>98%,标记化合物在多种缓冲液中放置24 h依然保持原有放化纯度。经过尾部静脉注射到小鼠体内后, 放射性主要积累在肝脏/肾脏部位,符合该探针在生物体内的代谢行为。结论：本研究实现了⁶⁴Cu-PSMA-617探针的快速标记并建立了其质量控制方法,⁶⁴Cu-PSMA-617具有较好的理化性质,体内分布研究确认了其具有较好的生物学性质,该研究结果可为其进一步用于前列腺癌诊疗的临床转化奠定基础。     

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.     

Preparation andBiodistribution of Myocardial Perfusion Imaging Agent 18F-TPT

⁹⁹Tc^m-sestamibi is typically used as amyocardial perfusion imaging agent for SPECT, however, the high uptake of liverand lung compromise the diagnostic accuracy. PET has higher spatial resolutionand quantitative measurement of myocardial tracer uptake. The lipophiliccationic compound, (4-[¹⁸F]fluorophenyl)triphenylphosphoniumion (¹⁸F-TPT)was synthesized as a potential positron emission tomography (PET) myocardialperfusion agent, biodistribution studies in the NH rats and Micro PET/CTimaging studies in the SD rats were performed. Total synthesis time was about 1h and the uncorrected synthesis yield was 2.5%, radiochemical purity was higherthan 99.5%, the product had good stability at room temperature. Biodistributiondata in rats showed high levels of accumulation in the heart with stableretention and rapid blood clearance, Heart-to-liver ratios at 30, 60, 90,and120 min were 33.1, 14.8, 25.7 and 17.3, respectively; Micro PET/CT imagingin the SD rat showed intense cardiac uptake and non-target tissues as liver,lung uptake were washed out quickly. The result show that ¹⁸F-TPT may have potential as amyocardial perfusion imaging agent for PET.     

靶向PSMA放射性小分子药物研究进展

前列腺癌(PCa)是男性死亡的常见诱因,严重危害着人们的生命健康。随着靶向前列腺特异性膜抗原（PSMA）的放射性药物在PET/CT和SPECT/CT中的应用,前列腺癌诊断的灵敏度与精确度得到了有效提高。本文首先对靶向PSMA小分子药物的核心结构单元进行介绍,然后重点介绍基于脲基发展而来的靶向PSMA放射性药物（放射性核素包括：⁶⁸Ga、¹⁸F、¹¹C、^99mTc、⁶⁴Cu、¹²³I、¹²⁵I、¹³¹I、¹⁷⁷Lu、²²⁵Ac、²¹³Bi和²¹²Pb等）,以及在前列腺癌中的诊断与治疗研究进展,最后对该研究领域进行总结与展望。