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Nat Protoc. 2016 Jun;11(6):1057-66. doi: 10.1038/nprot.2016.060. Epub 2016 May 12.

Radiolabeling of DOTA-like conjugated peptides with generator-produced (68)Ga and using NaCl-based cationic elution method.

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University Hospital Halle (Saale), Department of Nuclear Medicine, Halle, Germany.
Department of Nuclear Medicine, Erasmus MC Rotterdam, Rotterdam, the Netherlands.
Zentralklinik Bad Berka, Department of Nuclear Medicine/PET Center, Bad Berka, Germany.
Friedrich Schiller University of Jena, Institute of Organic and Macromolecular Chemistry, Jena, Germany.
Jena Center for Soft Matter (JCSM), Jena, Germany.
RadioMedix, Inc., Houston, Texas, USA.
Departments of Radiology and Radiation Oncology (Free Radical Radiation Biology Program), University of Iowa, Iowa City, Iowa, USA.


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).

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