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心肌灌注显像(myocardial perfusion imaging,MPI)是临床常用的无创性诊断心肌缺血的影像学方法,在冠心病诊断、疗效评价和预后判断中发挥着重要作用,是国内外认可的一项重要的检查技术[1]。目前国内主要采用SPECT进行MPI检查,常用显像剂为99Tcm-MIBI和99Tcm-替曲膦[2]。众多研究结果表明,SPECT MPI有一定的局限性,与PET相比其灵敏度较低,受膈肌和乳腺的衰减伪影影响较大,且传统SPECT无法进行心肌血流的绝对定量分析[3-4]。此外,PET MPI检查中患者所受辐射剂量更小[5]。但由于PET MPI中常用的显像剂为13N-NH3·H2O(13N-氨水),需要配备价格昂贵的医用回旋加速器,并且因其物理半衰期较短(9.98 min),导致患者显像的通过量低;另外,由于运动负荷显像很难进行,导致PET MPI的临床应用受到很大的限制,当前国内只有少数临床机构具备开展PET MPI的能力。因此,开发半衰期相对较长、适于配送的正电子心肌灌注显像剂已成为当前研究的热点之一[6],其中一种新型18F标记的心肌灌注显像剂18F-Flurpiridaz(BMS-747158)在国外已进入临床Ⅲ期研究阶段,其应用前景广阔[7-8]。目前国内尚未见此类显像剂在动物或人体显像的研究报道,为此,本研究探讨18F-Flurpiridaz的合成工艺,并初步研究其在正常巴马小型猪体内的MPI图像质量和体内分布特点。
18F-Flurpiridaz的制备及其在正常巴马小型猪PET/CT心肌灌注显像中的初步实验研究
Primary experimental study on 18F-flurpiridaz synthesis and its myocardial perfusion imaging through PET/CT in normal miniature pigs
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摘要:
目的 探讨合成18F-Flurpiridaz的优化方法,评估其在正常巴马小型猪PET/CT心肌灌注显像(MPI)中的分布情况。 方法 以18F取代2-叔丁基-4-氯-5-[4-(2-甲基磺酰基-乙氧基甲基)苯基甲氧基]哒嗪-3-哒嗪酮中的苯磺酸离去基团进行标记,通过高效液相色谱非梯度洗脱的方法纯化产物。5头正常巴马小型猪经耳缘静脉注射37 MBq 18F-Flurpiridaz后10 min行PET/CT MPI,并于注射后30和60 min进行PET/CT全身显像,观察显像剂在其体内主要脏器的摄取情况。 结果 18F-Flurpiridaz的制备时间约为50 min,非校正放射化学产率为40%,放射化学纯度>97%。MPI图像显示心肌细胞摄取明显,肝脏仅有少量摄取,肺基本无摄取,心肌图像质量好。全身显像中,显像剂注射后30 min,心肌和肾脏摄取明显,肌肉组织中有少量摄取,而其他组织器官均无明显摄取;显像剂注射后60 min,心脏内仍有较高摄取。 结论 实现并优化了18F-Flurpiridaz的自动化合成,为其临床应用奠定了基础。 -
关键词:
- 心肌灌注显像 /
- 氟放射性同位素 /
- Flurpiridaz /
- 正电子发射断层显像计算机体层摄影术 /
- 放射合成
Abstract:Objectve To explore the synthesis method of 18F-flurpiridaz and evaluate its ability for myocardial perfusion imaging (MPI) through PET/CT and bio-distribution in normal miniature pigs. Methods 18F-Flurpiridaz was prepared through the substitution of the toluene sulfonate leaving group of tert-butyl-4-chloro-5(4-(2-methyl(sulfonyl-ethoxymethyl)phenyl)methyl)pyridazin-3-one followed by radiolabeling with 18F. The product was isolated and purified by high performance liquid chromatography (HPLC) non-gradient elution. PET/CT MPI was performed 10 min after intravenous injection of 37 MBq 18F-flurpiridaz in five normal miniature pigs, and PET/CT whole-body scans were performed 30 and 60 min after injection to observe the bio-distribution. Results The total synthesis time (including HPLC separation) of 18F-flurpiridaz was approximately 50 min. The radiochemical yield was 40% (decay uncorrected), and the radiochemical purity was >97% (after HPLC purification). MPI results demonstrated that the radioactive uptake primarily accumulated in heart muscles, whereas little radioactivity was distributed throughout the liver and lungs. Moreover, the image quality was good. The whole-body PET/CT data showed high uptake in heart muscles and kidneys, whereas the skeleton muscle only had little radioactive uptake. No evident accumulations of activity in other organs were observed. 18F-Flurpiridaz had higher retention in the myocardium 60 min after injection. Conclusion The automatic synthesis of 18F-flurpiridaz is realized and optimized, which lays a foundation for its clinical application. -
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