title: Ethanol-Based Post-processing of Generator-Derived ⁶⁸Ga Toward Kit-Type Preparation of ⁶⁸Ga-Radiopharmaceuticals.
abstract: Post-processing by means of a cation-exchanger-based protocol is an efficient strategy for purification and concentration of generator-derived (68)Ga. It ensures the removal of (68)Ge before (68)Ga-radiopharmaceutical preparation and high labeling yields of (68)Ga-labeled radiopharmaceuticals for routine medical application.
  
  
  METHODS
  In an effort to overcome the problem associated with acetone in the currently applied method, we have investigated the feasibility of replacing it with ethanol. The purification of (68)Ga from coeluted metallic impurities ((68)Ge(4+), Fe(3+), Zn(2+), and Ti(4+)) on various cation-exchange columns has been investigated with a variety of post-processing solutions. As a proof of principle, the post-processed (68)Ga was used to radiolabel DOTATOC in combination with high-purity water and various buffer solutions.
  
  
  RESULTS
  An effective protocol for the processing of generator-produced (68)Ga on the basis of cation-exchange chromatography using EtOH/HCl medium has been developed. Up to 95% of the initially eluted (68)Ga activity can be collected in a 1-mL fraction of 90% EtOH/0.9N HCl after removal of (68)Ge-breakthrough in a washing step. The post-processed eluate has been used to radiolabel DOTATOC in yields of approximately 97% ± 0.25% at 80°C in 5 min.
  
  
  CONCLUSIONS
  The described novel protocol improves the radiolabeling efficiency and efficacy of DOTATOC, providing yields of greater than 99% (decay-corrected). As a result, further purification to separate the desired product from uncomplexed (68)Ga is not necessary. The developed post-processing and labeling protocols permit reliable and high-yield preparation of injectable (68)Ga-DOTATOC (or other (68)Ga-labeled radiopharmaceuticals) that are suitable for routine application. It is possible to incorporate this protocol into existing automated modules.
authors.affiliation: Institute of Nuclear Chemistry, Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Eppard
authors.affiliation: Institute of Nuclear Chemistry, Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Wuttke
authors.affiliation: Institute of Nuclear Chemistry, Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Philipp L
authors.initials: PL
authors.lastname: Nicodemus
authors.affiliation: Institute of Nuclear Chemistry, Johannes Gutenberg-University, Mainz, Germany frank.roesch@uni-mainz.de.
authors.forename: Frank
authors.initials: F
authors.lastname: Rösch
mesh_terms: D002411:Cation Exchange Resins / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods*; D000431:Ethanol / Q000737:chemistry*; D005710:Gallium Radioisotopes / Q000737:chemistry; D006851:Hydrochloric Acid / Q000737:chemistry; D007553:Isotope Labeling; D015282:Octreotide / Q000031:analogs & derivatives / Q000737:chemistry; D011786:Quality Control; D011854:Radiochemistry / Q000379:methods*; D019275:Radiopharmaceuticals / Q000737:chemistry*
chemical_list: D002411:Cation Exchange Resins; D005710:Gallium Radioisotopes; D019275:Radiopharmaceuticals; D000431:Ethanol; D006851:Hydrochloric Acid; D015282:Octreotide; C106246:Edotreotide
keywords: 68Ga; 68Ge; DOTATOC; ethanol; post-processing