Click-chemistry strategy for labeling antibodies with copper-64 via a cross-bridged tetraazamacrocyclic chelator scaffold

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We report a click-chemistry based modular strategy for antibody labeling with <sup>64</sup>Cu (t<inf>1/2</inf> = 12.7 h; β<sup>+</sup> 0.656 MeV, 17.4%; β<sup>-</sup> 0.573 MeV, 39%; EC 43%) under ambient condition utilizing a cross-bridged tetraazamacrocyclic (CB-TE2A) analogue, which otherwise requires harsh conditions that make the CB-TE2A analogues under-utilized for protein labeling despite the fact that they form kinetically inert copper complexes with high in vivo stability. Our strategy involves prelabeling a CB-TE2A based scaffold (CB-TE2A-1C) with <sup>64</sup>Cu and its subsequent reaction with an antibody via the tetrazine-norbornene mediated click chemistry. The effectiveness of this strategy was demonstrated by labeling two monoclonal antibodies, an anti-PSMA antibody (YPSMA-1) and a chimeric anti-phosphatidylserine antibody (Bavituximab). The immunoreactivity of the antibodies remained unchanged after the tetrazine modification and click-chemistry <sup>64</sup>Cu labeling. To further demonstrate the practicality of the modular <sup>64</sup>Cu labeling strategy, we tested positron emission tomography (PET) imaging of tumor with the <sup>64</sup>Cu-labeled bavituximab in a mouse xenograft model. The tumor visualization and uptake of the labeled antibody exhibited the versatility of the click-chemistry strategy.

Original languageEnglish (US)
Pages (from-to)782-789
Number of pages8
JournalBioconjugate Chemistry
Issue number4
Publication statusPublished - Apr 15 2015


ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Organic Chemistry
  • Pharmaceutical Science
  • Biomedical Engineering
  • Pharmacology

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