Zhang Zhuo, Ordonez Alvaro A, Smith-Jones Peter, Wang Hui, Gogarty Kayla R, Daryaee Fereidoon, Bambarger Lauren E, Chang Yong S, Jain Sanjay K, Tonge Peter J
Institute for Chemical Biology & Drug Discovery, Department of Chemistry and Department of Radiology, Stony Brook University, Stony Brook, New York, United States of America.
Center for Infection and Inflammation Imaging Research, Center for Tuberculosis Research and Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
PLoS One. 2017 Feb 2;12(2):e0170871. doi: 10.1371/journal.pone.0170871. eCollection 2017.
5-[18F]F-pyrazinamide (5-[18F]F-PZA), a radiotracer analog of the first-line tuberculosis drug pyrazinamide (PZA), was employed to determine the biodistribution of PZA using PET imaging and ex vivo analysis. 5-[18F]F-PZA was synthesized in 60 min using a halide exchange reaction. The overall decay-corrected yield of the reaction was 25% and average specific activity was 2.6 × 106 kBq (70 mCi)/μmol. The biodistribution of 5-[18F]F-PZA was examined in a pulmonary Mycobacterium tuberculosis mouse model, where rapid distribution of the tracer to the lung, heart, liver, kidney, muscle, and brain was observed. The concentration of 5-[18F]F-PZA was not significantly different between infected and uninfected lung tissue. Biochemical and microbiological studies revealed substantial differences between 5-F-PZA and PZA. 5-F-PZA was not a substrate for pyrazinamidase, the bacterial enzyme that activates PZA, and the minimum inhibitory concentration for 5-F-PZA against M. tuberculosis was more than 100-fold higher than that for PZA.
5-[¹⁸F]氟吡嗪酰胺（5-[¹⁸F]F-PZA）是一线抗结核药物吡嗪酰胺（PZA）的放射性示踪类似物，用于通过正电子发射断层扫描（PET）成像和离体分析来确定PZA的生物分布。5-[¹⁸F]F-PZA通过卤化物交换反应在60分钟内合成。反应经衰变校正后的总产率为25%，平均比活度为2.6×10⁶贝克勒尔（70毫居里）/微摩尔。在肺部结核分枝杆菌小鼠模型中研究了5-[¹⁸F]F-PZA的生物分布，观察到示踪剂迅速分布到肺、心脏、肝脏、肾脏、肌肉和大脑。感染和未感染的肺组织中5-[¹⁸F]F-PZA的浓度无显著差异。生化和微生物学研究揭示了5-F-PZA和PZA之间的显著差异。5-F-PZA不是吡嗪酰胺酶的底物，吡嗪酰胺酶是激活PZA的细菌酶，5-F-PZA对结核分枝杆菌的最低抑菌浓度比对PZA高100倍以上。
