题名 |
GMP全自動化生產:臺大醫院經驗分享 |
并列篇名 |
Fully Automated GMP Production of [Ga-68]Ga-DOTA-TOC for Somatostatin Receptor Imaging: NTUH Experience |
DOI |
10.6332/ANMMI.201909_32(3).0002 |
作者 |
黃雅瑤(Ya-Yao Huang);鄭媚方(Mei-Fang Cheng);張育寧(Yu-Ning Chang);顏若芳(Ruoh-Fang Yen) |
关键词 |
[Ga-68]Ga-DOTA-TOC ; 自動化生產 ; 生長激素抑制因子受體 ; GMP ; EP ; [Ga-68]Ga-DOTA-TOC ; automated production ; somatostatin receptors ; GMP ; EP |
期刊名称 |
核子醫學暨分子影像雜誌 |
卷期/出版年月 |
32卷3期(2019 / 09 / 01) |
页次 |
123 - 138 |
内容语文 |
繁體中文 |
中文摘要 |
背景:[Ga-68]Ga-DOTA-TOC,也被稱為[Ga-68]Ga-Edotreotide,是一種生長激素抑制因子受體的特異性放射性藥物,其相關專題論文已列入歐洲藥典中。臺大醫院正子製藥實驗室遵循藥品優良製造規範(Good Manufacturing Practice, GMP)製藥原則與《歐洲藥典》(European Pharmacopoeia, EP)專章之品管規範,實施[Ga-68]Ga-DOTA-TOC之生產,並且在臨床使用上也予以驗證。此研究的目的是將現有符合GMP標準的[Ga-68]Ga-DOTA-TOC全自動化生產結果與經驗加以整理,並彙整符合現行EP專章[Ga-68]Ga-DOTA-TOC之品管測試,以期與其他正子中心分享。方法:[Ga-68]Ga-DOTA-TOC乃是使用商業化之產生器模組(Modular-Lab eazy, Eckert & Ziegler Eurotope GmbH, Berlin, Germany)進行全自動化合成。其中,[Ga-68]Ga-DOTA-TOC合成流程是以0.1N HCl洗提醫藥級Ge-68/Ga-68產生器得到符合EP專章規格之[Ga-68]GaCl_3。之後,[Ga-68] GaCl_3直接進入產生器中進行合成。首先,[Ga-68]GaCl_3經SCX管柱進行純化後,進入反應瓶與DOTA-TOC acetate相混和,並在適當的緩衝溶液中進行[Ga-68]Ga標誌反應。待反應完畢後,最終產物再以生理食鹽水進行稀釋,並以0.22μm無菌過濾膜進行無菌過濾,即可得臨床可用之 [Ga-68]Ga-DOTA-TOC注射液。結果:目前,我們實驗室已成功合成[Ga-68]Ga-DOTA-TOC注射液,並予以藥物品管及臨床影像驗證。[Ga-68]Ga-DOTA-TOC注射液合成時間15分鐘,產率73 ± 5%(end of synthesis, EOS)(n = 3),每批的放射化學純度和比活度分別為≥ 95%和1,083 ± 256 GBq/μmol。結論:本研究中,我們已成功以商業化模組進行[Ga-68]Ga-DOTA-TOC自動化生產,其所得產物亦符合EP專章所列規格。所有[Ga-68]Ga-DOTA-TOC注射液之製造過程,皆符合GMP精神,目前也已經通過衛生福利部食品藥物管理署(Taiwan Food and Drug Administration)查核,對未來臨床上的使用將有相當大的助益。 |
英文摘要 |
Introduction: [Ga-68]Ga-DOTA-TOC (also known as [Ga-68]Ga-Edotreotide) is a somatostatin receptors - specific radiopharmaceutical and the corresponding monograph has been listed in European Pharmacopoeia (EP). According to the GMP principles and EP specification, the verification is required prior to clinical use. The aim of this study is to setup a fully-automated production of GMP-compliant [Ga-68]Ga-DOTA-TOC. Moreover, the complete QC tests of [Ga-68]Ga-DOTA-TOC based on EP monograph are prerequisites for clinical use in research projects with ethics approval. Methods: In this study, [Ga-68]Ga-DOTA-TOC was automatically radio-synthesized with Modular-Lab Eazy module. Briefly, [Ga-68]GaCl_3 was eluted from pharmagrade Ge-68/Ga-68 generator with 0.1 N HCl and was then post-processed with a SCX cartridge. Followed by the collection of [Ga-68]GaCl_3 eluent in reaction vial, Ga-68 labelling of DOTA-TOC acetate was conducted in the buffer mixture at 110°C. After cooling, the final product was diluted with saline and then was sterilized by filtration through an inline 0.22 μm filter. Results: The syntheses of [Ga-68]Ga-DOTA-TOC were successfully validated under GMP conditions, resulting in radiochemical yield of 73 ± 5% (end of synthesis) within 15 min (n = 3) of synthesis time. Radiochemical purity and specific activity of each batch were ≥ 95% and 1,083 ± 256 GBq/μmol, respectively. Conclusions: In this study, [Ga-68]Ga-DOTA-TOC was automatically produced in compliance with GMP and EP. More recently, on-site manufacturing of [Ga-68]Ga-DOTA-TOC at National Taiwan University Hospital has been approved by Taiwan's Food and Drug Administration. It will be much beneficial to produce qualified [Ga-68]Ga- DOTA-TOC for clinical and pre-clinical use in Taiwan. |
主题分类 |
醫藥衛生 >
基礎醫學 醫藥衛生 > 內科 工程學 > 核子工程 |