[(64) Cu]-labelled trastuzumab: optimisation of labelling by DOTA and NODAGA conjugation and initial evaluation in mice

Christina Schjoeth-Eskesen, Carsten Haagen Nielsen, Søren Heissel, Peter Højrup, Paul Robert Hansen, Nic Gillings, Andreas Kjaer

14 Citations (Scopus)

Abstract

The human epidermal growth factor receptor-2 (HER2) is overexpressed in 20-30% of all breast cancer cases, leading to increased cell proliferation, growth and migration. The monoclonal antibody, trastuzumab, binds to HER2 and is used for treatment of HER2-positive breast cancer. Trastuzumab has previously been labelled with copper-64 by conjugation of a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator. The aim of this study was to optimise the (64) Cu-labelling of DOTA-trastuzumab and as the first to produce and compare with its 1,4,7-triazacyclononane, 1-glutaric acid-5,7 acetic acid (NODAGA) analogue in a preliminary HER2 tumour mouse model. The chelators were conjugated to trastuzumab using the activated esters DOTA mono-N-hydroxysuccinimide (NHS) and NODAGA-NHS. (64) Cu-labelling of DOTA-trastuzumab was studied by varying the amount of DOTA-trastuzumab used, reaction temperature and time. Full (64) Cu incorporation could be achieved using a minimum of 10-µg DOTA-trastuzumab, but the fastest labelling was obtained after 15 min at room temperature using 25 µg of DOTA-trastuzumab. In comparison, 80% incorporation was achieved for (64) Cu-labelling of NODAGA-trastuzumab. Both [(64) Cu]DOTA-trastuzumab and [(64) Cu]NODAGA-trastuzumab were produced after purification with radiochemical purities of >97%. The tracers were injected into mice with HER2 expressing tumours. The mice were imaged by positron emission tomography and showed high tumour uptake of 3-9% ID/g for both tracers.

Original languageEnglish
JournalJournal of Labelled Compounds and Radiopharmaceuticals
Volume58
Issue number6
Pages (from-to)227-33
Number of pages7
ISSN0362-4803
DOIs
Publication statusPublished - 30 May 2015

Keywords

  • Acetates
  • Animals
  • Antibodies, Monoclonal, Humanized
  • Heterocyclic Compounds, 1-Ring
  • Mice
  • Organometallic Compounds
  • Protein Binding
  • Radiopharmaceuticals
  • Receptor, ErbB-2
  • Tissue Distribution

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