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

Dirk Mueller; Wouter A P Breeman; Ingo Klette; Michael Gottschaldt; Andreas Odparlik; Manfred Baehre; Izabela Tworowska; Michael K Schultz

doi:10.1038/nprot.2016.060

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

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

Dirk Mueller, Wouter A P Breeman, Ingo Klette, Michael Gottschaldt, Andreas Odparlik, Manfred Baehre, Izabela Tworowska and Michael K Schultz

Nature protocols, Vol.11(6), pp.1057-1066

06/2016

DOI: 10.1038/nprot.2016.060

PMCID: PMC5506837

PMID: 27172166

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https://www.ncbi.nlm.nih.gov/pmc/articles/5506837View

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Abstract

Gallium-68 ( 68 Ga) is a generator-produced radionuclide with a short half-life ( t ½ = 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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Title: Subtitle: Radiolabeling of DOTA-like conjugated peptides with generator-produced 68Ga and using NaCl-based cationic elution method
Creators: Dirk Mueller - 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
Wouter A P Breeman - 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
Ingo Klette - 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
Michael Gottschaldt - 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
Andreas Odparlik - 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
Manfred Baehre - 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
Izabela Tworowska - 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
Michael K Schultz - 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
Resource Type: Journal article
Publication Details: Nature protocols, Vol.11(6), pp.1057-1066
DOI: 10.1038/nprot.2016.060
PMID: 27172166
PMCID: PMC5506837
NLM abbreviation: Nat Protoc
ISSN: 1754-2189
eISSN: 1750-2799
Language: English
Date published: 06/2016
Academic Unit: Radiology; Stead Family Department of Pediatrics; Radiation Oncology
Record Identifier: 9984216592402771

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