Top

Molecular Imaging and Biology

Published in:

01-12-2018 | Research Article

Optimization of a Labeling and Kit Preparation Method for Ga-68 Labeled DOTATATE, Using Cation Exchange Resin Purified Ga-68 Eluates Obtained from a Tin Dioxide ⁶⁸Ge/⁶⁸Ga Generator

Authors: Deidré Prince, Daniel Rossouw, Sietske Rubow

Published in: Molecular Imaging and Biology | Issue 6/2018

Abstract

Purpose

The aim of this study was to optimize a radiolabeling method using cationic processed Ga-68 eluates from a SnO₂-based ⁶⁸Ge/⁶⁸Ga generator, followed by the development of DOTA-Tyr³-Thre⁸-octreotide (DOTATATE) kits.

Procedures

Diluted generator eluates were adsorbed on a SCX resin and desorbed with acidified 5 M NaCl solution. Optimized labeling conditions were determined by variation of pH, using 35 μg DOTATATE and sodium acetate buffer. DOTATATE kits were developed based on optimized radiolabeling conditions, were labeled, and evaluated.

Results

Optimized labeling conditions resulted in a radiolabeling efficiency of around 99 % and radiochemical yield of almost 85 %. Different kit preparation methods did not significantly influence the radiolabeling results. Kits were found to be stable over 3 months.

Conclusion

A labeling method using SCX-processed Ga-68 eluates was optimized. DOTATATE kits specifically for these SCX-processed Ga-68 eluates were successfully formulated. A post-labeling Sep-Pak C18 purification should be optional.

Fani M, André JP, Maecke HR (2008) ⁶⁸Ga-PET: a powerful generator-based alternative to cyclotron-based PET radiopharmaceuticals. Contrast Media Mol Imaging 3:67–77CrossRef

Maecke HR, Hofmann M, Haberkorn U (2005) ⁶⁸Ga-labeled peptides in tumor imaging. J Nucl Med 46:172S–178SPubMed

Breeman WAP, Verbruggen AM (2007) The ⁶⁸Ge/⁶⁸Ga generator has high potential, but when can we use ⁶⁸Ga-labelled tracers in clinical routine? Eur J Nucl Med Mol Imaging 34:978–981CrossRef

Roesch F (2012) Maturation of a key resource—the germanium-68/gallium-68 generator: development and new insights. Curr Radiopharm 5:202–211CrossRef

Breeman WAP, de Jong M, de Blois E, Bernard BF, Konijnenberg M, Krenning EP (2005) Radiolabelling DOTA-peptides with ⁶⁸Ga. Eur J Nucl Med Mol Imaging 32:478–485CrossRef

de Blois E, Sze Chan H, Naidoo C, Prince D, Krenning EP, Breeman WAP (2011) Characteristics of SnO₂-based ⁶⁸Ge/⁶⁸Ga generator and aspects of radiolabelling DOTA-peptides. Appl Radiat Isot 69:308–315CrossRef

Rossouw DD, Breeman WAP (2012) Scaled-up radiolabelling of DOTATATE with ⁶⁸Ga eluted from a SnO₂-based ⁶⁸Ge/⁶⁸Ga generator. Appl Radiat Isot 70:171–175CrossRef

Roesch F, Zhernosekov K, Filosofov D et al (2006) Processing of Ge-68/Ga-68 generator eluates for labeling of biomolecules via bifunctional chelators. J Nucl Med 47:162P

Zhernosekov KP, Filosofov DV, Baum RP, Aschoff P, Bihl H, Razbash AA, Jahn M, Jennewein M, Rosch F (2007) Processing of generator-produced ⁶⁸Ga for medical application. J Nucl Med 48:1741–1748CrossRef

10.

Asti M, De Pietri G, Fraternali A et al (2008) Validation of ⁶⁸Ge/⁶⁸Ga generator processing by chemical purification for routine clinical application of ⁶⁸Ga-DOTATOC. Nucl Med Biol 35:721–724CrossRef

11.

Ocak M, Antretter M, Knopp R, Kunkel F, Petrik M, Bergisadi N, Decristoforo C (2010) Full automation of ⁶⁸Ga labelling of DOTA-peptides including cation exchange prepurification. Appl Radiat Isot 68:297–302CrossRef

12.

Mueller D, Klette I, Baum RP, Gottschaldt M, Schultz MK, Breeman WAP (2012) Simplified NaCl based ⁶⁸Ga concentration and labeling procedure for rapid synthesis of ⁶⁸Ga radiopharmaceuticals in high radiochemical purity. Bioconjug Chem 23:1712–1717CrossRef

13.

Schultz MK, Mueller D, Baum RP, Leonard Watkins G, Breeman WAP (2013) A new automated NaCl based robust method for routine production of gallium-68 labeled peptides. Appl Radiat Isot 76:46–54CrossRef

14.

Martin R, Jüttler S, Müller M, Wester HJ (2014) Cationic eluate pretreatment for automated synthesis of [⁶⁸Ga]CPCR4.2. Nucl Med Biol 41:84–89CrossRef

15.

Seemann J, Eppard E, Waldron BP, Ross TL, Roesch F (2015) Cation exchange-based post-processing of ⁶⁸Ga eluate: a comparison of three solvent systems for labelling of DOTATOC, NO2AP^BP and DATA^m. Appl Radiat Isot 98:54–59CrossRef

16.

Mukherjee A, Pandey U, Chakravarty R, Sarma HD, Dash A (2014) Development of single vial kits for preparation of ⁶⁸Ga-labelled peptides for PET imaging of neuroendocrine tumours. Mol Imaging Biol 16:550–557CrossRef

17.

Mukherjee A, Pandey U, Chakravarty R, Sarma HD, Dash A (2014) Single vial kit formulation for preparation of PET radiopharmaceutical: ⁶⁸Ga-DOTA-TOC. J Radioanal Nucl Chem 302:1253–1258CrossRef

18.

Das T, Bhadwal M, Sarma HD, Banerjee S (2014) Formulation and radiochemical evaluation of a freeze-dried mixed peptide kit for the preparation of ⁶⁸Ga-labeled peptides for PET imaging of somatostatin receptor positive neuroendocrine cancers. J Radioanal Nucl Chem 302:1259–1264CrossRef

19.

Asti M, Iori M, Capponi PC, Rubagotti S, Fraternali A, Versari A (2015) Development of a simple kit-based method for preparation of pharmaceutical-grade ⁶⁸Ga-DOTATOC. Nucl Med Commun 36(5):502–510PubMed

20.

Mukherjee A, Korde A, Sarma HD, Samuel G (2014) Single vial formulation for theranostic radiopharmaceutical preparation. J Radioanal Nucl Chem 302:889–894CrossRef

21.

Prince D, Rossouw D, Davids C, Rubow S (2017) Development and evaluation of user-friendly single vial DOTA-peptide kit formulations, specifically designed for radiolabelling with ⁶⁸Ga from a tin dioxide ⁶⁸Ge/⁶⁸Ga generator. Mol Imaging Biol 19:817–824CrossRef

22.

Hofmann M, Maecke H, Börner AR, Weckesser E, Schöffski P, Oei M, Schumacher J, Henze M, Heppeler A, Meyer G, Knapp W (2001) Biokinetics and imaging with the somatostatin receptor PET radioligand ⁶⁸Ga-DOTATOC: preliminary data. Eur J Nucl Med 28:1751–1757CrossRef

23.

Henze M, Schuhmacher J, Hipp P, Kowalski J, Becker DW, Doll J, Mäcke HR, Hofmann M, Debus J, Haberkorn U (2001) PET imaging of somatostatin receptors using [⁶⁸Ga]DOTA-D-Phe¹-Tyr³-octreotide: first results in patients with meningiomas. J Nucl Med 42:1053–1056PubMed

24.

Decristoforo C, Knopp R, von Guggenberg E, Rupprich M, Dreger T, Hess A, Virgolini I, Haubner R (2007) A fully automated synthesis for the preparation of ⁶⁸Ga-labelled peptides. Nucl Med Commun 28:870–875CrossRef

25.

Velikyan I, Beyer GJ, Långström B (2004) Microwave-supported preparation of ⁶⁸Ga bioconjugates with high specific radioactivity. Bioconjug Chem 15:554–560CrossRef

26.

Velikyan I, Sundin A, Eriksson B, Lundqvist H, Sörensen J, Bergström M, Långström B (2010) In vivo binding of [⁶⁸Ga]-DOTATOC to somatostatin receptors in neuroendocrine tumours—impact of peptide mass. Nucl Med Biol 37:265–275CrossRef

27.

Velikyan I, Xu H, Nair M, Hall H (2012) Robust labeling and comparative preclinical characterization of DOTA-TOC and DOTA-TATE. Nucl Med Biol 39:628–639CrossRef

28.

Meyer GJ, Hofmann M, Kühn J et al (2003) ⁶⁸Ga-labelled DOTA-derivatised peptide ligands. J Labelled Comp Radiopharm 46:S273CrossRef

Title: Optimization of a Labeling and Kit Preparation Method for Ga-68 Labeled DOTATATE, Using Cation Exchange Resin Purified Ga-68 Eluates Obtained from a Tin Dioxide 68Ge/68Ga Generator
Authors: Deidré Prince
Daniel Rossouw
Sietske Rubow
Publication date: 01-12-2018
Publisher: Springer International Publishing
Published in: Molecular Imaging and Biology / Issue 6/2018
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-018-1195-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Optimization of a Labeling and Kit Preparation Method for Ga-68 Labeled DOTATATE, Using Cation Exchange Resin Purified Ga-68 Eluates Obtained from a Tin Dioxide ⁶⁸Ge/⁶⁸Ga Generator

Abstract

Purpose

Procedures

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Procedures

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 6/2018

Multispectral Photoacoustic Imaging of Tumor Protease Activity with a Gold Nanocage-Based Activatable Probe

Metabolic and Molecular Imaging with Hyperpolarised Tracers

Investigation of cis-4-[18F]Fluoro-D-Proline Uptake in Human Brain Tumors After Multimodal Treatment

Noise-Induced Variability of Immuno-PET with Zirconium-89-Labeled Antibodies: an Analysis Based on Count-Reduced Clinical Images

Imaging VEGF Receptors and αvβ3 Integrins in a Mouse Hindlimb Ischemia Model of Peripheral Arterial Disease

Current and Emerging Preclinical Approaches for Imaging-Based Characterization of Atherosclerosis