放射性核素标记的生长抑素类似物可与神经内分泌肿瘤(NETs)细胞表面的生长抑素受体(SSTR)特异性结合,因此可用作NETs显像或治疗的靶点.本研究通过双功能螯合剂1,4,7-三氮杂环壬烷-1,4,7-三乙酸(NOTA)螯合Al18 F复合物设计合成了一种新型靶向SSTR的放射性探针[Al18 F]NOTA-GABA-KE108.[Al18 F]NOTA-GABA-KE108的合成时间为30 min左右,标记率为60％ ～80％(未校正),经Sep-pak C-18 light柱纯化后,放化纯度>95％.[Al18 F]NOTA-GABA-KE108呈水溶性(lg P=-1.67±0.07),在生理盐水及小牛血清中孵育2 h后放化纯度>95％.在SSTR阳性AR42J和BON1肿瘤细胞中,[Al18 F]NOTA-GABA-KE108探针与受体结合的亲和力(Kd)分别为(1.34±0.60)、(1.45±0.51)μmol/L,且能被特异性抑制,展现出较高的SSTR靶向能力.[Al18 F]NOTA-GABA-KE108在正常KM小鼠肝脏和肾脏中具有高放射性聚集,说明探针主要通过肝肾代谢,在SSTR表达较高的肾上腺和胰腺中有较高的放射性浓集,在BON1荷瘤鼠体内也具有相同的代谢途径,且在血液和肌肉中的本底低,而在肿瘤部位有较高的放射性摄取,具有高的靶与非靶比.以上结果为进一步研究Al18 F复合物标记的生长抑素类似物作为生长抑素受体阳性肿瘤显像剂提供了实验依据.

BackgroundRadionuclide labeled somatostatin analogs can specifically bind to somatostatin receptors (SSTRs) on the cell surface of neuroendocrine tumors (NETs), hence be used for imaging or treatment of NETs.PurposeThis study aims to label glycosylated KE108 protein with 18F nuclide, and to investigate the distributions and PET imaging of this probe in mice in vivo.MethodsA novel 18F-radiolabeled somatostatin analogue probe Gluc-Lys([Al18F]NOTA)-KE108 was designed and synthesized, which linked 18F nuclide and glycosylated KE108 protein by coupling bifunctional chelator (NOTA) to target SSTR positive tumors. The in vitro physicochemical properties, in vitro cell binding, ex vivo biodistribution and in vivo imaging of Gluc-Lys([Al18F]NOTA)-KE108 were further investigated to evaluate the SSTR targeting ability and feasibility of PET imaging in the diagnosis of NETs.ResultsThe efficiency of Gluc-Lys([Al18F]NOTA)-KE108 obtained with moderate labelling is (30±5)% without corrected (n=6), and the radiochemical purity is higher than >95%. The radiochemical yield is ((20±5)%, uncorrected) (n=6), and the total synthesis time is about 20 min. The specific activity is more than 1.37 GBq∙μmol-1. The probe shows expected nanomolar binding affinity in SSTR-positive AR42J and BON1 tumor cells, which Kd values are (152.3±49.1) nmol∙L-1 and (45.5±13.6) nmol∙L-1, respectively, and can be specifically inhibited, showing high SSTR targeting ability. In PET imaging of AR42J tumor bearing mice, Gluc-Lys([Al18F]NOTA)-KE108 has a high uptake of radioactivity and a high ratio of tumor to muscle uptake.ConclusionsGluc-Lys([Al18F]NOTA)-KE108 has high hydrophilicity and good stability in vitro, hence be served as a potential imaging agent for SSTR-positive tumors.

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-NaFPET显像和99Tcm-亚甲基二磷酸盐(99Tcm-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8h和30℃下放置10 h所有检验结果均无明显变化;18F-NaF PET和99Tcm-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99Tcm-MDP,而99Tcm-MDP需在给药后2h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99Tcm-MDP,可明显提高检查流通量和诊断效能.

目的 氟[18F]化钠是一种正电子计算机断层显像(PET)骨显像剂,主要用于诊断成骨活性有改变的病灶.本实验旨在考查氟[18F]化钠的药动学性质,并通过PET显像研究其诊断效果.方法 首先制备氟[18F]化钠注射液,并对其进行质量控制,然后研究其在新西兰兔体内的血液清除情况和血浆蛋白结合率,进行氟[18F]化钠PET和99Tcm-MDP SPECT显像的随机对照试验,并对显像效果进行比较.结果 制备了氟[18F]化钠注射液,检验结果均符合质控要求.氟[18F]化钠在血液中清除相半衰期为37 rnin,在体内的清除率(CL)为56 mL·min-1·kg-,血浆蛋白结合率为0.57％.2种显像方式均可见全身骨骼,但氟[18F]化钠PET显像给药后30 min就可获得良好的显像效果,骨骼部位显示更为清晰,骨骼部位与肌肉的放射性摄取比明显高于99Tcm-MDP.结论 氟[18F]化钠PET骨显像性能优于99Tcm-MDP SPECT,本实验为氟[18F]化钠PET用于骨显像的临床应用提供了实验依据.