通过直接放射性氟化和基于柱盒的纯化，实现[F]DCFPyL的简化且稳健的一步法放射性合成。

Simplified and robust one-step radiosynthesis of [ F]DCFPyL via direct radiofluorination and cartridge-based purification.

作者信息

Dornan Mark H, Simard José-Mathieu, Leblond Antoine, Juneau Daniel, Delouya Guila, Saad Fred, Ménard Cynthia, DaSilva Jean N

机构信息

Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada.

Département de Radiologie, Radio-oncologie et Médecine Nucléaire, Université de Montréal, Montréal, Québec, Canada.

出版信息

J Labelled Comp Radiopharm. 2018 May 2. doi: 10.1002/jlcr.3632.

DOI:10.1002/jlcr.3632

PMID:29722070

Abstract

[ F]DCFPyL is a clinical-stage PET radiotracer used to image prostate cancer. This report details the efficient production of [ F]DCFPyL using single-step direct radiofluorination, without the use of carboxylic acid-protecting groups. Radiolabeling reaction optimization studies revealed an inverse correlation between the amount of precursor used and the radiochemical yield. This simplified approach enabled automated preparation of [ F]DCFPyL within 28 minutes using HPLC purification (26% ± 6%, at EOS, n = 4), which was then scaled up for large-batch production to generate 1.46 ± 0.23 Ci of [ F]DCFPyL at EOS (n = 7) in high molar activity (37 933 ± 4158 mCi/μmol, 1403 ± 153 GBq/μmol, at EOS, n = 7). Further, this work enabled the development of [ F]DCFPyL production in 21 minutes using an easy cartridge-based purification (25% ± 9% radiochemical yield, at EOS, n = 3).

摘要

[F]DCFPyL是一种用于前列腺癌成像的临床阶段正电子发射断层显像（PET）放射性示踪剂。本报告详细介绍了使用单步直接放射性氟化法高效生产[F]DCFPyL的过程，该方法无需使用羧酸保护基团。放射性标记反应优化研究表明，所用前体的量与放射化学产率呈负相关。这种简化方法能够在28分钟内通过高效液相色谱（HPLC）纯化自动制备[F]DCFPyL（在合成结束时，放射化学产率为26%±6%，n = 4），随后扩大规模进行大批量生产，在合成结束时（n = 7）以高摩尔活度（37 933±4158 mCi/μmol，1403±153 GBq/μmol，n = 7）生成1.46±0.23 Ci的[F]DCFPyL。此外，这项工作还实现了使用基于简易柱盒的纯化方法在21分钟内生产[F]DCFPyL（在合成结束时，放射化学产率为25%±9%，n = 3）。