A Comparison Study between LAL Endotoxin Test Methodologies of PET Radiotracers: Endosafe®-PTS^(TM) System and Kinetic Chromogenic Analysis

Abstract

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.