Affinity-Guided Conjugation to Antibodies for Use in Positron Emission Tomography

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Mikkel B. Skovsgaard
  • ,
  • Troels E. Jeppesen, Københavns Universitet, Department of Clinical Physiology, Rigshospitalet, Copenhagen
  • ,
  • Michael R. Mortensen
  • ,
  • C.H. Nielsen, Københavns Universitet, Department of Clinical Physiology, Rigshospitalet, Copenhagen
  • ,
  • J. Madsen, Københavns Universitet, Department of Clinical Physiology, Rigshospitalet, Copenhagen
  • ,
  • Andreas Kjaer, Københavns Universitet, Department of Clinical Physiology, Rigshospitalet, Copenhagen
  • ,
  • Kurt V. Gothelf

The radionuclide copper-64 is widely used in combination with biomolecules, such as antibodies, for positron emission tomography (PET). Copper-64 is ideal for the imaging of biomolecules with long circulation times due to its relatively long half-life, and when conjugated to an antibody, specific cells can be targeted in vivo. Here, we have prepared a trastuzumab-chelator conjugate by using affinity-guided conjugation, in which an azide was attached to the antibody prior to a strain promoted azide-alkyne cycloaddition reaction with DBCO-PEG 4 -NOTA. The conjugate was benchmarked against a standard nonspecific labeled trastuzumab-NOTA conjugate. The conjugates were tested for incorporation of copper-64, stability in buffer and plasma, and tumor targeting in vivo using PET imaging of mice with xenograft tumors expressing HER2. Both conjugates showed good incorporation of copper-64 and a high stability with less than 10% degradation after 36 h. Furthermore, both conjugates showed accumulation at the tumor site with mean uptake of 7.2 ± 2.4%ID/g and 5.2 ± 1.3%ID/g after 40 h for the affinity-guided labeled trastuzumab and the nonspecific labeled trastuzumab, respectively.

Original languageEnglish
JournalBioconjugate Chemistry
Volume30
Issue3
Pages (from-to)881-887
Number of pages7
ISSN1043-1802
DOIs
Publication statusPublished - Mar 2019

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