title: Radiosynthesis of clinical doses of ⁶⁸Ga-DOTATATE (GalioMedix™) and validation of organic-matrix-based ⁶⁸Ge/⁶⁸Ga generators.
abstract: BACKGROUND
  68Ga-DOTATATE is a radiolabeled peptide-based agonist that targets somatostatin receptors overexpressed in neuroendocrine tumors. Here, we present our results on validation of organic matrix 68Ge/68Ga generators (ITG GmbH) applied for radiosynthesis of the clinical doses of 68Ga-DOTATATE (GalioMedixTM).
  
  
  METHODS
  The clinical grade of DOTATATE (25 μg±5 μg) compounded in 1 M NaOAc at pH=5.5 was labeled manually with 514±218 MBq (13.89±5.9 mCi) of 68Ga eluate in 0.05 N HCl at 95°C for 10 min. The radiochemical purity of the final dose was validated using radio-TLC. The quality control of clinical doses included tests of their osmolarity, endotoxin level, radionuclide identity, filter integrity, pH, sterility and 68Ge breakthrough.
  
  
  RESULTS
  The final dose of 272±126 MBq (7.35±3.4 mCi) of 68Ga-DOTATATE was produced with a radiochemical yield (RCY) of 99%±1%. The total time required for completion of radiolabeling and quality control averaged approximately 35 min. This resulted in delivery of 50%±7% of 68Ga-DOTATATE at the time of calibration (not decay corrected).
  
  
  CONCLUSIONS
  68Ga eluted from the generator was directly applied for labeling of DOTA-peptide with no additional pre-concentration or pre-purification of isotope. The low acidity of 68Ga eluate allows for facile synthesis of clinical doses with radiochemical and radionuclide purity higher than 98% and average activity of 272±126 MBq (7.3±3 mCi). There is no need for post-labeling C18 Sep-Pak purification of final doses of radiotracer. Advances in knowledge and implications for patient care. The clinical interest in validation of 68Galabeled agents has increased in the past years due to availability of generators from different vendors (Eckert-Ziegler, ITG, iThemba), favorable approach of U.S. FDA agency to initiate clinical trials, and collaboration of U.S. centers with leading EU clinical sites. The list of 68Ga-labeled tracers evaluated in clinical studies should growth because of the sensitivity of PET technique, the simplicity of the shakebake approach for the dose preparation and reliability of 68Ge/68Ga generators. Our studies have confirmed the reproducible elution profile, and high reliability of ITG GmbH generators required for routine doses preparation according to FDA recommendations.
authors.affiliation: RadioMedix Inc., Houston, TX, USA. Electronic address: itworowska@radiomedix.com.
authors.forename: Izabela
authors.initials: I
authors.lastname: Tworowska
authors.affiliation: RadioMedix Inc., Houston, TX, USA.
authors.forename: David
authors.initials: D
authors.lastname: Ranganathan
authors.affiliation: RadioMedix Inc., Houston, TX, USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Thamake
authors.affiliation: RadioMedix Inc., Houston, TX, USA.
authors.forename: Ebrahim
authors.initials: E
authors.lastname: Delpassand
authors.affiliation: RadioMedix Inc., Houston, TX, USA.
authors.forename: Alireza
authors.initials: A
authors.lastname: Mojtahedi
authors.affiliation: Department of Radiology, University of Iowa, Iowa City, IA USA; Department of Radiation Oncology, University of Iowa, Iowa City, IA USA.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Schultz
authors.affiliation: ITM Isotopen Technologien München AG, Garching, Germany.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Zhernosekov
authors.affiliation: ITM Isotopen Technologien München AG, Garching, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Marx
mesh_terms: D060326:Chemistry Techniques, Synthetic; D005857:Germanium / Q000737:chemistry*; D006801:Humans; D007474:Ion Exchange; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D011829:Radiation Dosage; D011854:Radiochemistry / Q000379:methods*; D011868:Radioisotopes
chemical_list: D009942:Organometallic Compounds; D011868:Radioisotopes; D005857:Germanium; C513399:gallium Ga 68 dotatate
keywords: (68)Ga-DOTATATE; (68)Ge breakthrough; (68)Ge/(68)Ga generator; Neuroendocrine tumors; Positron emission tomography (PET); Quality control of PET-tracers doses