Lindberg Anton, Boyle Amanda J, Tong Junchao, Harkness Michael B, Garcia Armando, Tran Tritin, Zhai Dongxu, Liu Fang, Donnelly David J, Vasdev Neil
Azrieli Centre for Neuro-Radiochemistry, Centre for Addiction and Mental Health, Toronto, ON, Canada.
Brain Health Imaging Centre, Centre for Addiction and Mental Health, Campbell Family Mental Health Research Institute, Toronto, ON, Canada.
Front Nucl Med. 2021 Nov 12;1:772289. doi: 10.3389/fnume.2021.772289. eCollection 2021.
Ibrutinib is a first-generation Bruton's tyrosine kinase (BTK) inhibitor that has shown efficacy in autoimmune diseases and has consequently been developed as a positron emission tomography (PET) radiotracer. Herein, we report the automated radiosynthesis of [C]ibrutinib through C-carbonylation of the acrylamide functional group, by reaction of the secondary amine precursor with [C]CO, iodoethylene, and palladium-NiXantphos. [C]Ibrutinib was reliably formulated in radiochemical yields of 5.4% ± 2.5% (non-decay corrected; = 9, relative to starting [C]CO), radiochemical purity >99%, and molar activity of 58.8 ± 30.8 GBq/μmol (1.55 ± 0.83 Ci/μmol). Preliminary PET/magnetic resonance imaging with [C]ibrutinib in experimental autoimmune encephalomyelitis (EAE) mice showed a 49% higher radioactivity accumulation in the spinal cord of mice with EAE scores of 2.5 vs. sham mice.
依鲁替尼是第一代布鲁顿酪氨酸激酶（BTK）抑制剂，已在自身免疫性疾病中显示出疗效，因此被开发为正电子发射断层扫描（PET）放射性示踪剂。在此，我们报告了通过丙烯酰胺官能团的碳羰基化反应，使仲胺前体与[C]CO、碘乙烯和钯 - NiXantphos反应，实现[C]依鲁替尼的自动化放射性合成。[C]依鲁替尼的可靠制剂的放射化学产率为5.4%±2.5%（未进行衰变校正；n = 9，相对于起始[C]CO），放射化学纯度>99%，摩尔活度为58.8±30.8 GBq/μmol（1.55±0.83 Ci/μmol）。在实验性自身免疫性脑脊髓炎（EAE）小鼠中用[C]依鲁替尼进行的初步PET/磁共振成像显示，EAE评分为2.5的小鼠脊髓中的放射性积累比假手术小鼠高49%。
