- 期刊
A Comparison Study between LAL Endotoxin Test Methodologies of PET Radiotracers: Endosafe®-PTS^(TM) System and Kinetic Chromogenic Analysis
正子藥物之內毒素LAL測試方法之比較：Endosafe®-PTS^(TM)系統與動力呈色法
摘要
背景：細菌內毒素檢測是正子藥物品管程序中極重要的一環。然而過長的檢測時間往往侷限了短半衰期正子藥物之臨床應用與發展。本研究希望可以評估可攜式內毒素快速定量系統（potable test system, PTS）於正子藥物之內毒素檢測的應用性，並且與目前台大醫院正子中心臨床使用的動力呈色法（kinetic chromogenic assay, KCA）方法作一比較。方法：由6位品管人員分別以本中心自行生產的F-18 FDG、C-11 PiB和N-13 NH3正子藥物進行PTS與KCA兩種不同方法之內毒素含量檢測。其中，針對PTS法乃是選用內毒素偵測敏感度為0.05EU/mL的測試孔匣。此外，為了驗證此兩種內毒素測試方法結果的準確度及六位品管人員操作程序之可信度，因此也進行美國藥典核可之標準內毒素（reference standard endotoxin, RSE）的盲樣測試。結果：不論是KCA或PTS，所得到的正子產品之內毒素含量檢測結果相似，儘管檢測時間以PTS明顯較短（約需16～17分鐘）。然而，根據RSE之盲樣測試結果顯示，KCA法中其標準曲線所需使用的試驗內毒素容易影響其檢測結果，例如不適當的保存條件。結論：針對正子藥物的內毒素含量品管（尤其是具短半衰期的藥物），PTS能和KCA一樣提供準確之內毒素測量結果。但是PTS在操作便利和反應快速的特性，不僅將更簡化製藥人員之工作流程和避免不易發現的錯誤，並有助於未來正子藥物之發展及臨床應用。
並列摘要
Background: The pyrogen test represents an important parameter for the quality control (QC) of PET tracers. However, the standard test proposed by the U.S. Pharmacopeia using limulus amebocyte lysates takes too long (about 1 h) for short-lived PET tracers. Endosafe® Portable Test System (PTS) has been approved by FDA and was claimed that it takes approximately 15 min to complete test procedure. The aim of this study was to evaluate PTS performance for PET tracers and head-to-head comparison with kinetic chromogenic analysis (KCA) that routinely used in NTUH PET center. Methods: With PTS and the conventional assay method, Lonza KCA assay systems, both experiments were performed on 3 consecutive batches of on-site produced F-18 FDG, C-11 PiB and N-13 NH3 by 6 different executors. All samples were tested with PTS method using 0.05~5.0EU/mL sensitivity cartridges. Additionally, for purpose to verify the accuracy of results from these two endotoxin test methods and the reliability regarding operative procedures among 6 QC staff, fabricated endotoxinpositive samples containing a fixed concentration of USP validated reference standard endotoxin (RSE) were also prepared and tested for blind testing. Results: The results of endotoxin detection among these two methods involving KCA and PTS were similar in most cases, although PTS exhibited significantly shorter time in testing (about 16~17 minutes required). However, results of blind test indicate that the control standard endotoxin used in KCA method has significant impact on the test results, such as inappropriate storage conditions of control standard endotoxin, and the KCA measurement is the most time-consuming method among these three methods. Conclusions: TPTS provided as reliable results as KCA method for endotoxin test and even more rapidly, therefore, is most suitable for short-lived PET radiotracers. Thus, the use of PTS will simplify the routine QC procedures of short-lived PET radiopharmaceuticals and prevent undetectable errors. Also, it will be of benefit to clinical application and future development of PET radiotracers.