Nkepang Gregory N, Hedrick Andria F, Awasthi Vibhudutta, Gali Hariprasad
Department of Pharmaceutical Sciences, College of Pharmacy, The University of Oklahoma Health Sciences Center, 1110 N. Stonewall Avenue, Room 301, Oklahoma City, OK 73117, USA.
Department of Pharmaceutical Sciences, College of Pharmacy, The University of Oklahoma Health Sciences Center, 1110 N. Stonewall Avenue, Room 301, Oklahoma City, OK 73117, USA.
Bioorg Med Chem Lett. 2016 Jan 15;26(2):479-483. doi: 10.1016/j.bmcl.2015.11.091. Epub 2015 Nov 25.
para-[(18)F]fluorohippurate ([(18)F]PFH) is a renal tubular agent suitable for conducting positron emission tomography (PET) renography. [(18)F]PFH is currently synthesized by a four-step two-pot procedure utilizing a classical prosthetic group, N-succinimidyl-4-[(18)F]fluorobenzoate, followed by glycine conjugation. Considering the short half-life of fluorine-18 (110min), it is important to reduce the number of synthetic steps and overall production time for successful translation of any fluorine-18 radiopharmaceutical in to clinical practice. Here, we report a new two-step one-pot procedure using a novel spirocyclic iodonium ylide precursor for producing a dose of [(18)F]PFH suitable for human use in 45min including HPLC purification with an overall decay-corrected radiochemical yield of 46.4±2.9% (n=3) and radiochemical purity of >99%.
对-[(18)F]氟马尿酸盐([(18)F]PFH)是一种适用于正电子发射断层扫描(PET)肾造影的肾小管显像剂。[(18)F]PFH目前是通过一种四步双瓶程序合成的，该程序使用经典的辅助基团N-琥珀酰亚胺基-4-[(18)F]氟苯甲酸酯，然后进行甘氨酸偶联。考虑到氟-18的半衰期较短(110分钟)，对于任何氟-18放射性药物成功转化为临床应用而言，减少合成步骤的数量和总体生产时间都很重要。在此，我们报告一种新的两步单瓶程序，该程序使用新型螺环碘鎓叶立德前体，在45分钟内制备出一剂适用于人体的[(18)F]PFH，包括通过高效液相色谱法纯化，总体衰变校正后的放射化学产率为46.4±2.9%(n = 3)，放射化学纯度>99%。
