Inhibition evaluation for a 20-min endotoxin limit test on FDG

In chemical quality control tests for 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG), gel time is inversely related to endotoxin concentration. Solutions for positive product control (PPC) and positive water control (PWC) should contain a highly concentrated endotoxin level. The aims of our study were to derive an endotoxin concentration that causes PPC and PWC to gel and to evaluate inhibitory effects caused by FDG on gel formation in PPC and PWC test solutions.

At expiration, the maximum administered total dose (in millilitres) of FDG should contain fewer than 175 endotoxin units (EU). Our average batch volume of FDG is 15 ml; thus, the minimum endotoxin limit should be 12 EU x ml(-1) . Twelve tubes were tested for each of four concentrations. Inhibition was assessed using Limulus amoebocyte lysate reagent, depyrogenated vials, and pyrogen-free sterile micropipette tips. Each study was performed with four groups of solutions: decayed 18F-FDG, negative control, PPC and PWC.

In the study of undiluted FDG, seven of 50 PPC vials at 12 EU x ml(-1) did not gel. The lowest endotoxin concentration that consistently gelled at 20 min was 4 EU x ml(-1) . In the sample tested for inhibition using PPC tubes at 4 EU x ml(-1) , 49 tubes gelled at 20 min, and one did not.

The inhibition rate improved between undiluted (i.e., 7/50 (14%)) and diluted (i.e., 1/50 (2%)) FDG PPC trials (P=0.03). However, given that 1 of 50 trials failed for diluted FDG PPC, we conclude that inhibition still occurs and there is a 95% chance that the inhibition rate could be as high as 11% or as low as 0% on repetition of the experiment.