Luo Zonghua, Gu Jiwei, Dennett Robert C, Gaehle Gregory G, Perlmutter Joel S, Chen Delphine L, Benzinger Tammie L S, Tu Zhude
Department of Radiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Department of Radiology, Washington University School of Medicine, St. Louis, MO, 63110, USA; Department of Neurology, Neuroscience, Physical Therapy and Occupational Therapy, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Appl Radiat Isot. 2019 Oct;152:30-36. doi: 10.1016/j.apradiso.2019.06.029. Epub 2019 Jun 20.
Automated synthesis of a radiopharmaceutical 3-((2-fluoro-4-(5-(2'-methyl-2-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)-1,2,4-oxadiazol-3-yl)benzyl) (methyl-C)amino)propanoic acid ([C]CS1P1) for PET imaging sphingosine-1 phosphate receptor 1 (S1P1) was accomplished by a two-step-one-pot procedure in a Siemens CTI methylation automated module using TR-19 cyclotron. The synthesis of [C]CS1P1 was successfully validated under current Good Manufacturing Practices (cGMP) conditions, resulting in a consistent average radiochemical yield of ∼15%, molar activity of ∼3129 GBq/μmol (decay corrected to end of bombardment, EOB), and radiochemical purity > 95%. The radiopharmaceutical product meets all quality control criteria for human use for an Investigational New Drug (IND) application to permit human studies.
通过两步一锅法，在使用TR - 19回旋加速器的西门子CTI甲基化自动化模块中，实现了用于正电子发射断层显像（PET）的鞘氨醇-1-磷酸受体1（S1P1）放射性药物3-((2-氟-4-(5-(2'-甲基-2-(三氟甲基)-[1,1'-联苯]-4-基)-1,2,4-恶二唑-3-基)苄基)(甲基-C)氨基)丙酸([C]CS1P1)的自动化合成。[C]CS1P1的合成在现行药品生产质量管理规范（cGMP）条件下成功得到验证，平均放射化学产率约为15%，摩尔活度约为3129 GBq/μmol（衰变校正至轰击结束，EOB），放射化学纯度>95%。该放射性药物产品符合用于新药临床试验申请（IND）的人体使用的所有质量控制标准，以允许进行人体研究。
