新型细胞死亡显像剂18F-FPDuramycin的自动化合成  

Automated synthesis of novel cell death imaging tracer ^(18)F-FPDuramycin

作　　者：要少波[1,2] 胡孔珍[2] 唐刚华[2] 梁祥[2] 姜申德[1] 

机构地区：[1]天津大学药物科学与技术学院,天津300072 [2]中山大学附属第一医院核医学科,广州510080

出　　处：《核技术》2014年第3期44-49,共6页Nuclear Techniques

基　　金：国家高科技计划(863计划)专题课题(No.2008AA02Z430);国家自然基金项目(No.30970856、No.81371584、No.81201116);广东省科技计划项目(No.2010B031600054);广州市科技计划重点项目(No.2011J5200025);教育部留学回国启动基金(教外司留[2010]609号);天津市科技支撑计划国际合作项目(No.11ZCGHHZ00800);天津大学自主创新基金No.1207;吴阶平医学基金(No.320675013203)资助

摘　　要：通过引入氟标记辅助基团尝试多肽耐久霉素(Duramycin)的18F标记,探索其放化标记的自动化合成过程。使用国产PET-MF-2V-IT-I合成模块,先通过三步简单的反应,合成辅助基团4-nitrophenyl 2-[18F]fluoropropionate(18F-NFP);随后将18F-NFP与耐久霉素反应生成18F-FPDuramycin,产物通过固相萃取的方法进行纯化,并对相应反应条件(溶剂、碱和反应时间)做了正交试验以确定其最佳条件。从18F离子起始合成18F-NFP共需80 min,未经衰变矫正,放化收率为(25±5)%(n=10);以18F-NFP为原料合成至18F-FPDuramycin共需20 min,未经衰变矫正,放化收率为(70±3)%(n=8),终产物18F-FPDuramycin的放化纯度大于99%,比活度为(23.7±13.7)GBq·?mol-1(n=10)。通过使用"二锅法"自动化合成18F-FPDuramycin,操作简便,收率稳定,质量控制检测满足放射性药物质量管理条例规定,能满足科研和临床正电子断层显像的要求。Background： The noninvasive imaging of cell death plays an important role in the evaluation of degenerative diseases and detection of tumor treatments. Duramycin, a peptide with 19-amino acid, is produced by Streptoverticillium cinnamoneus. It binds specifically to phosphatidylethanolamine （PE）, a novel molecular target for cell death. Purpose： The aim is to develop a synthetic method to label duramycin using lSF ion. The automated synthesis was carried out by multi-step procedure on the modified PET-MF-2V-IT-I synthesizer. Methods： Firstly, the prosthetic group of 4-nitrophenyl 2-[18F]fluoropropionate （18F＋NFP） was automatically synthesized by a convenient three-step procedure. Secondly, 18F-FPDuramycin was synthesized by conjunction of 18F-NFP with duramycin, which was purified by a solid-phase extraction cartridge. Orthogonal test was performed to confirm the suitable reaction conditions （solvent, base and temperature）. Results： The radiochemical yields of 18F-NFP were （25±5）% （n=10, decay-uncorrected） based on [18F]fluoride in 80 min. 18F-FPDuramycin was obtained with yield of （70±3）% （n=8, decay-uncorrected） based on 18F-NFP within 20 min. The radiochemical purity of 18F-FPDuramycin was greater than 99% and the specific activity was greater than （23.7±13.7） GBq. umol-1 （n=10）. Conclusion： 18F-FPDuramycin injection is easy to be prepared with ＂two-pot reaction＂ and is a promising radiotracer used for the clinical and scientific study on laositron emission tomograohy （PET） imaging.

关 键 词：自动化合成 18F-FPDuramycin 细胞死亡显像剂 磷脂酰乙醇胺 放化标记 

分 类 号：TL923[核科学技术—核燃料循环与材料]