以Eckert-Ziegler模組系統自動合成[C-11]PiB程序之最佳化

The Optimization of the Synthesis of 2-(4-N-[C-11] methylaminophenyl)-6-hydroxybenzothiazole ([C-11] PiB) With Eckert&Ziegler Modular System

張智偉(Chi-Wei Chang) ； 洪鈞澤(Chun-Tse Hung) ； 楊宛甄(Wan-Jen Yang) ； 陳世沛(Shih-Pei Chen) ； 張文議(Wen-Yi Chang) ； 劉仁賢(Ren-Shyan Liu) ； 黃文盛(Wen-Sheng Huang) ； 彭南靖(Nan-Jing Peng)

《核子醫學暨分子影像雜誌》 36卷2期 (2023/06) Pp. 58-70

https://doi.org/10.6332/ANMMI.202306_36(2).0002

摘要

背景：在臺北榮總正子中心例行性地合成[C-11]匹茲堡化合物-B（C11 Pittsburgh Compound B, [C-11] PiB）供神經內科失智病患使用，進行臨床試驗研究。注射[C-11]PiB於患者時，保持高莫耳活度（molar activity）的[C-11]PiB是造影成功的重要條件。本文目的是利用一修改的EZ模組系統（Eckert-Ziegler modular, EZ）以進行[C-11]PiB自動化生產製程，且應用於[C-11]PiB的常規性合成而滿足臨床研究的需求。本文將詳細描述[C-11]PiB常規生產程序所做的模組修改與相關生產參數。方法：將加速器生產之[C-11]CO_2送入EZ模組系統中生產[C-11]三氟甲磺酸甲酯（[C-11]CH_3OTf），在EZ模組系統的高效率液相層析儀「管路」中與前驅物進行甲基化反應和最終的調劑，全自動合成[C-11]PiB。結果：[C-11]PiB的放射化學產率為9.66 ± 2.02%（基於衰變未校正的[C-11] CO_2，n = 22），莫耳活度為156.71 ± 4.56 GBq/μmol（end of synthesis）（n = 22）。放射化學純度超過99%。結論：對EZ模組化系統進行了一些修改，採用了「管路」方法。穩定了[C-11]PiB的莫耳活度，也穩定了總放射活性。透過EZ模組系統的修改與參數最佳化，可以獲得足夠放射活性和高莫耳活度的[C-11]PiB，而應用於臨床研究。透過這些方法，C-11-甲基化反應將可以應用於其他C-11-示蹤劑的自動放射合成。

關鍵字

[C-11]PiB ； Eckert-Ziegler（EZ）模組系統 ； 莫耳活度

並列摘要

Background: [C-11] Pittsburgh Compound-B (PiB) is now almost routinely used to perform clinical studies for patients in the neurological department at Taipei Veterans General Hospital positron emission tomography (PET) center. It is important to have high molar activity of [C-11] PiB when it is injected into the patients. The aim of this work was to modify an Eckert-Ziegler (EZ) modular system for the routine synthesis of [C-11] PiB to meet the demand of clinical studies. Some modifications of [C-11] PiB routine production procedures are described in detail. Methods: The fully automated synthesis of [C-11] PiB starting from [C-11] CO_2 is reported. [C-11] methyl triflate was produced in the semi-preparative HPLC loop in EZ modular system. Methylation reactions and the final formulation were performed using the EZ modular system. Results: The radiochemical yield of [C-11] PiB was 9.66 ± 2.02% (based on [C-11] CO_2 decay uncorrected, n = 22) and the molar activity was 156.71 ± 4.56 GBq/μmol (end of synthesis) (n = 22). The radiochemical purity exceeded 99%. Conclusions: We adopted the "loop" method and modified some procedures in the modular system. The molar activity of [C-11] PiB was getting stable and so was the total radioactivity of [C-11] PiB. Sufficient radioactivity of [C-11] PiB with high molar activity could be achieved by EZ modular system for clinical studies. The C-11-methylation reaction could be applied to other radiosynthesis of the C-11-tracer via the loop method.

並列關鍵字

[C-11] PiB ； Eckert-Ziegler modular system ； molar activity