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- Title
[<sup>64</sup>Cu]-labelled trastuzumab: optimisation of labelling by DOTA and NODAGA conjugation and initial evaluation in mice.
- Authors
Schjoeth ‐ Eskesen, Christina; Nielsen, Carsten Haagen; Heissel, Søren; Højrup, Peter; Hansen, Paul Robert; Gillings, Nic; Kjaer, Andreas
- 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 64Cu-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. 64Cu-labelling of DOTA-trastuzumab was studied by varying the amount of DOTA-trastuzumab used, reaction temperature and time. Full 64Cu 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 64Cu-labelling of NODAGA-trastuzumab. Both [64Cu]DOTA-trastuzumab and [64Cu]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.
- Subjects
EPIDERMAL growth factor receptors; BREAST cancer research; CELL proliferation; CELL migration; TRASTUZUMAB; TRIAZACYCLONONANE; GLUTARIC acid; THERAPEUTICS
- Publication
Journal of Labelled Compounds & Radiopharmaceuticals, 2015, Vol 58, Issue 6, p227
- ISSN
0362-4803
- Publication type
Article
- DOI
10.1002/jlcr.3287