[18F]AlF-NOTA-P-L-Lys6-GnRH的自动化合成及初步Micro-PET/CT显像

Automated radiosynthesis and preliminary Micro-PET/CT imaging of [18F]AlF-NOTA-P-L-Lys6-GnRH

通过固相合成法合成新型促性腺激素释放激素(Gonadotropin Releasing Hormone,GnRH)衍生物,在商业模块上用[18F]AlF标记法自动化标记该衍生物,所标记示踪剂进一步在PC-3前列腺荷瘤模型裸鼠体内进行小动物PET/CT(Positron Emission Tomography/Computed Tomography)显像。L-Lys^6-GnRH的6-赖氨酸末端氮位上用聚乙二醇(Polyethylene Glycol,PEG)链接三-叔-丁基2,2′,2″(- 1,4,7,10-四氮杂环十二烷-1,4,7-三基)三乙酸(tri-tert-butyl 2,2′,2″(- 1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetate,NOTA)官能团合成一种新的GnRH衍生物(NOTA-P-GnRH),在国产模块PET-MF-2V-IT-I中通过一锅一步反应自动化制备[18F]AlF-NOTA-P-L-GnRH,自动化合成时间在 35 min 以内,衰变校正后产率(25±6)%,放射化学纯度>95%,比活度 8~30 GBq·μmol^-1(n=6)。进一步用[^18F]AlF-NOTA-P-L-Lys^6-GnRH在PC-3前列腺荷瘤模型裸鼠体内进行小动物PET/CT动态显像,肿瘤部位清晰可见,具有高的肿瘤与肌肉摄取比值,动态活度与时间曲线显示示踪剂主要通过肾脏排泄。结果表明:[18F]AlF标记法在商业模块中的自动化生产操作简便、高效可靠,[18F]AlF-NOTA-P-L-Lys^6-GnRH是PC-3前列腺肿瘤的潜在显象剂。

[Backgroud] Gonadotropin releasing hormone (GnRH) receptor is overexpressed in many human tumors and is currently used as a target for molecular imaging.[Purpose] This study aims to design and synthesize a new 18F-labeled GnRH peptide by automatic radiosynthesis for preliminary Micro-PET/CT imaging.[Methods][18F]AlF-NOTA-P-L-Lys^6 -GnRH was automated radiolabeled with 18F by using Al 18F complex on the modified PET-MF-2V-IT-I synthesis module. The stability of [18F]AlF-NOTA-P-L-Lys^6 -GnRH was incubated in phosphate buffer saline (PBS) at 37 ℃ and the octanol/water partition coefficient was studied. The dynamic Micro-positron emission tomography (PET) study of [18F]AlF-NOTA-P-L-Lys^6 -GnRH in nude mice bearing PC-3 cancer was carried out.[Results] The total radiochemical synthesis and purification of [18F]AlF-NOTA-P-L-Lys^6 -GnRH was completed in 35 min with a decay-corrected yield of (25±6)% and a specific activity of 8~30 GBq·μmol^-1 (n=6). The logP value of [^18F]AlF-NOTA-P-L-Lys^6 -GnRH was -2.70±0.06 and the tracer was stable in phosphate-buffered saline for 2 h. Dynamic PET imaging analysis revealed that [18F]AlF-NOTA-P-L-Lys^6 -GnRH was clearly delineated in PC-3 xenografted tumor with high tumor-to-muscle ratios and excreted mainly through the kidneys.[Conclusion][18F]AlF-NOTA-P-L-Lys^6- GnRH was an efficient automated production of commercially available synthetic modules that could be used as a potential PET tracer for the imaging PC-3 prostate tumors.