title: A portable test system for determination of bacterial endotoxins in 18F-FDG, 99mTc, and lyophilized reagents for labeling with 99mTc.
abstract: A rapid quantitative kinetic chromogenic test in an automated portable test system has been developed for in-process and end-product determination of bacterial endotoxins in water using the Limulus amebocyte lysate. The aim of this work was to validate the method for (18)F-FDG, (99m)Tc, and the lyophilized reagents methylene diphosphonic acid (MDP) and pyrophosphate for labeling with (99m)Tc radiopharmaceuticals with no interfering factors.
  
  
  METHODS
  Experiments were performed on 3 consecutive batches of (18)F-FDG, (99m)Tc, MDP, and pyrophosphate produced at the Nuclear Energy and Research Institute of São Paulo, Brazil, using a portable test system. The maximum valid dilution (=500) was calculated to establish the extent of dilution to avoid interfering test conditions.
  
  
  RESULTS
  Better results were obtained above a 1:5 dilution factor for (18)F-FDG and (99m)Tc, 1:20 for MDP, and 1:100 for pyrophosphate. The requirements of the test were satisfied (R ≤ 0.980, recovery of product positive control between 50% and 200%, and coefficient variation of samples < 25%), and the endotoxin concentration was lower than the lowest concentration of the standard curve (0.05 endotoxin unit mL(-1)) and therefore less than the established limit in pharmacopoeias.
  
  
  CONCLUSIONS
  The portable test system is a rapid, simple, and accurate technique using the quantitative kinetic chromogenic method for bacterial endotoxin determination. For this reason, the test is practical for radiopharmaceutical uses and tends to be the method of choice for the pyrogen test. For (18)F-FDG, (99m)Tc, MDP, and pyrophosphate, the validation was successfully performed.
authors.affiliation: Nuclear Energy and Research Institute (IPEN-CNEN/SP), Radiopharmacy Directory-DIRF, São Paulo, Brazil. ntfukumo@ipen.br
authors.forename: Neuza T O
authors.initials: NT
authors.lastname: Fukumori
authors.forename: Domingos G
authors.initials: DG
authors.lastname: de Campos
authors.forename: Adriana V F
authors.initials: AV
authors.lastname: Massicano
authors.forename: Nilda P S
authors.initials: NP
authors.lastname: de Pereira
authors.forename: Constancia P G
authors.initials: CP
authors.lastname: da Silva
authors.forename: Margareth M N
authors.initials: MM
authors.lastname: Matsuda
mesh_terms: D000818:Animals; D011756:Diphosphates / Q000378:metabolism*; D004164:Diphosphonates / Q000378:metabolism*; D004731:Endotoxins / Q000378:metabolism*; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism*; D005612:Freeze Drying; D006737:Horseshoe Crabs / Q000382:microbiology; D007202:Indicators and Reagents / Q000378:metabolism; D007553:Isotope Labeling / Q000379:methods*; D007700:Kinetics; D015609:Organotechnetium Compounds / Q000378:metabolism*; D019275:Radiopharmaceuticals / Q000378:metabolism; D015203:Reproducibility of Results
chemical_list: D011756:Diphosphates; D004164:Diphosphonates; D004731:Endotoxins; D007202:Indicators and Reagents; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; C027474:methylene diphosphonate