title: Radiolabeling of DOTA-like conjugated peptides with generator-produced (68)Ga and using NaCl-based cationic elution method.
abstract: Gallium-68 ((68)Ga) is a generator-produced radionuclide with a short half-life (t½ = 68 min) that is particularly well suited for molecular imaging by positron emission tomography (PET). Methods have been developed to synthesize (68)Ga-labeled imaging agents possessing certain drawbacks, such as longer synthesis time because of a required final purification step, the use of organic solvents or concentrated hydrochloric acid (HCl). In our manuscript, we provide a detailed protocol for the use of an advantageous sodium chloride (NaCl)-based method for radiolabeling of chelator-modified peptides for molecular imaging. By working in a lead-shielded hot-cell system,(68)Ga(3+) of the generator eluate is trapped on a cation exchanger cartridge (100 mg, ∼8 mm long and 5 mm diameter) and then eluted with acidified 5 M NaCl solution directly into a sodium acetate-buffered solution containing a DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) or DOTA-like chelator-modified peptide. The main advantages of this procedure are the high efficiency and the absence of organic solvents. It can be applied to a variety of peptides, which are stable in 1 M NaCl solution at a pH value of 3-4 during reaction. After labeling, neutralization, sterile filtration and quality control (instant thin-layer chromatography (iTLC), HPLC and pH), the radiopharmaceutical can be directly administered to patients, without determination of organic solvents, which reduces the overall synthesis-to-release time. This procedure has been adapted easily to automated synthesis modules, which leads to a rapid preparation of (68)Ga radiopharmaceuticals (12-16 min).
authors.affiliation: University Hospital Halle (Saale), Department of Nuclear Medicine, Halle, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Mueller
authors.affiliation: Department of Nuclear Medicine, Erasmus MC Rotterdam, Rotterdam, the Netherlands.
authors.forename: Wouter A P
authors.initials: WA
authors.lastname: Breeman
authors.affiliation: Zentralklinik Bad Berka, Department of Nuclear Medicine/PET Center, Bad Berka, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Klette
authors.affiliation: Friedrich Schiller University of Jena, Institute of Organic and Macromolecular Chemistry, Jena, Germany.|Jena Center for Soft Matter (JCSM), Jena, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Gottschaldt
authors.affiliation: University Hospital Halle (Saale), Department of Nuclear Medicine, Halle, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Odparlik
authors.affiliation: University Hospital Halle (Saale), Department of Nuclear Medicine, Halle, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Baehre
authors.affiliation: RadioMedix, Inc., Houston, Texas, USA.
authors.forename: Izabela
authors.initials: I
authors.lastname: Tworowska
authors.affiliation: Departments of Radiology and Radiation Oncology (Free Radical Radiation Biology Program), University of Iowa, Iowa City, Iowa, USA.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Schultz
mesh_terms: D005710:Gallium Radioisotopes / Q000737:chemistry*; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry*; D007553:Isotope Labeling / Q000379:methods*; D010455:Peptides / Q000737:chemistry* / Q000302:isolation & purification*; D012965:Sodium Chloride / Q000737:chemistry*
chemical_list: D005710:Gallium Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring; D010455:Peptides; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D012965:Sodium Chloride