title: The strange case of the [13N]NH3: validation of the production process for human use.
abstract: OBJECTIVE
  PET radiopharmaceuticals are often injected in patients before all quality controls are performed and before sterility results are available. We propose a process validation to produce very safe and pure [N]NH3 for human use.
  
  
  METHODS
  [N]NH3 was produced in the cyclotron target. Online purification was performed by anionic exchange resin. All the production steps were subjected to a sterility test. Some additional controls were added to those required by the monograph.
  
  
  RESULTS
  The radiochemical yield of the syntheses was 26.3 and 61.5% corrected for decay, with a radiochemical purity of 100%. In addition to quality controls requested by the European Pharmacopeia monograph, we carefully analyzed the product for the presence of possible contaminants. Some elements, mainly metals, were found in very low amounts at concentrations in the range of ppb. The radionuclidic purity was verified. The achievement of the parameters of osmolality, by addition of saline solution to the preparation, made the analysis of chemical purity difficult and worsened the measurement of radiochemical purity by high performance liquid chromatography. Only pH control is necessary before administration to patients and therefore a safe production process was set up to prevent microbiological contamination. All phases were carefully standardized, starting from in-target production of [N]NH3, to final splitting in the syringes. Sterility tests showed no bacterial growth, indicating the safety of the production process.
  
  
  CONCLUSIONS
  All our syntheses followed the monograph indications and were optimal to obtain PET imaging of a patient's myocardium.
authors.affiliation: aDepartment of Nuclear Medicine bBiotechnology Laboratory cMedical Physics Department dUnit of Occupational Health and Industrial Hygiene, Civic Hospital of Brescia eDepartment of Medical and Surgical Specialties, Radiological Sciences and Public Health, Section of Nuclear Medicine fDepartment of Molecular and Translational Medicine gUnit of Occupational Health and Industrial Hygiene, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Statuto
authors.forename: Elisa
authors.initials: E
authors.lastname: Galli
authors.forename: Francesco
authors.initials: F
authors.lastname: Bertagna
authors.forename: Elena
authors.initials: E
authors.lastname: Migliorati
authors.forename: Isabella
authors.initials: I
authors.lastname: Zanella
authors.forename: Diego
authors.initials: D
authors.lastname: Di Lorenzo
authors.forename: Antonio
authors.initials: A
authors.lastname: De Agostini
authors.forename: Carlo
authors.initials: C
authors.lastname: Rodella
authors.forename: Pietro
authors.initials: P
authors.lastname: Apostoli
authors.forename: Luigi
authors.initials: L
authors.lastname: Caimi
authors.forename: Raffaele
authors.initials: R
authors.lastname: Giubbini
authors.forename: Giorgio
authors.initials: G
authors.lastname: Biasiotto
mesh_terms: D000641:Ammonia / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009590:Nitrogen Radioisotopes; D009994:Osmolar Concentration; D011786:Quality Control; D011854:Radiochemistry / Q000379:methods*; D019275:Radiopharmaceuticals / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry; D013242:Sterilization
chemical_list: D009590:Nitrogen Radioisotopes; D019275:Radiopharmaceuticals; D012997:Solvents; D000641:Ammonia