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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.

Author information

1
University Hospital Halle (Saale), Department of Nuclear Medicine, Halle, Germany.
2
Department of Nuclear Medicine, Erasmus MC Rotterdam, Rotterdam, the Netherlands.
3
Zentralklinik Bad Berka, Department of Nuclear Medicine/PET Center, Bad Berka, Germany.
4
Friedrich Schiller University of Jena, Institute of Organic and Macromolecular Chemistry, Jena, Germany.
5
Jena Center for Soft Matter (JCSM), Jena, Germany.
6
RadioMedix, Inc., Houston, Texas, USA.
7
Departments of Radiology and Radiation Oncology (Free Radical Radiation Biology Program), University of Iowa, Iowa City, Iowa, USA.

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).

PMID:
27172166
PMCID:
PMC5506837
DOI:
10.1038/nprot.2016.060
[Indexed for MEDLINE]
Free PMC Article

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