Eriksson Jonas, Van Kooij Rolph, Schuit Robert C, Froklage Femke E, Reijneveld Jaap C, Hendrikse N Harry, Windhorst Albert D
Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands; PET Centre, Uppsala University Hospital, Uppsala, Sweden; Preclinical PET Platform, Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden.
J Labelled Comp Radiopharm. 2015 Mar;58(3):122-6. doi: 10.1002/jlcr.3251. Epub 2015 Feb 17.
Temozolomide is a chemotherapeutic drug that is mainly used in the treatment of primary glioblastoma multiforme and recurrent high-grade glioma. Here, we report an efficient good manufacturing practice compliant method for the synthesis of [3-N-(11) C-methyl]temozolomide from 3-N-hydroxymethyl temozolomide that cleaves off formaldehyde in situ and becomes activated towards alkylation with [(11) C]methyl iodide. The labelling method was developed for an on-going patient study in which the predictive value of [3-N-(11) C-methyl]temozolomide and positron emission tomography on the outcome of temozolomide treatment is being investigated. The precursor was reacted with [(11) C]methyl iodide in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene in acetonitrile, heated at stepwise increasing temperature. Purification by semipreparative HPLC with pharmaceutical grade eluent and filtration gave approximately 10 mL sterile product solution ready for injection containing 1.55 ± 0.38 GBq (n = 5), the specific activity was 88 ± 25 GBq/µmol and the radiochemical purity was 98.5 ± 1.9%. (13) C-NMR spectroscopy confirmed the labelled position after colabelling with (11) C and (13) C.
替莫唑胺是一种化疗药物，主要用于治疗原发性多形性胶质母细胞瘤和复发性高级别胶质瘤。在此，我们报告一种符合药品生产质量管理规范的高效合成方法，该方法可从3-N-羟甲基替莫唑胺合成[3-N-(11)C-甲基]替莫唑胺，其能原位裂解甲醛并对用[(11)C]甲基碘进行烷基化反应变得具有活性。该标记方法是为一项正在进行的患者研究而开发的，该研究正在探究[3-N-(11)C-甲基]替莫唑胺和正电子发射断层扫描对替莫唑胺治疗结果的预测价值。前体在乙腈中于1,8-二氮杂双环[5.4.0]十一碳-7-烯存在下与[(11)C]甲基碘反应，逐步升温加热。通过使用医药级洗脱液的半制备高效液相色谱法进行纯化并过滤，得到约10 mL可供注射的无菌产品溶液，其活度为1.55±0.38 GBq（n = 5），比活度为88±25 GBq/µmol，放射化学纯度为98.5±1.9%。(13)C-核磁共振光谱法在与(11)C和(13)C共标记后确认了标记位置。
