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Photochemical Conjugation and One-Pot Radiolabelling of Antibodies for Immuno-PET


Patra, Malay; Eichenberger, Larissa S; Fischer, Gregor; Holland, Jason P (2019). Photochemical Conjugation and One-Pot Radiolabelling of Antibodies for Immuno-PET. Angewandte Chemie Internationale Edition, 58(7):1928-1933.

Abstract

Monoclonal antibodies (mAbs), immunoglobulin fragments, and other proteins are important scaffolds in the development of radiopharmaceuticals for diagnostic immuno‐positron emission tomography (immuno‐PET) and targeted radioimmunotherapy (RIT). Conventional methods for radiolabelling proteins with metal ions such as 68Ga, 64Cu, 89Zr, and 90Y require multi‐step procedures involving pre‐purification, functionalisation with a chelate, and subsequent radiolabelling. Standard coupling chemistries are time‐consuming, difficult to automate, and involve synthesis, isolation, and storage of an intermediate, new molecular entity (the conjugated mAb) whose biochemical properties can differ from those of the parent protein. To circumvent these issues, we developed a photoradiochemical approach that uses fast, chemoselective, light‐induced protein modification under mild conditions with novel metal‐ion‐binding chelates derivatised with aryl azide (ArN3) groups. Experiments show that one‐pot photochemical conjugation and radiolabelling of formulated mAbs can be achieved in <20 min.

Abstract

Monoclonal antibodies (mAbs), immunoglobulin fragments, and other proteins are important scaffolds in the development of radiopharmaceuticals for diagnostic immuno‐positron emission tomography (immuno‐PET) and targeted radioimmunotherapy (RIT). Conventional methods for radiolabelling proteins with metal ions such as 68Ga, 64Cu, 89Zr, and 90Y require multi‐step procedures involving pre‐purification, functionalisation with a chelate, and subsequent radiolabelling. Standard coupling chemistries are time‐consuming, difficult to automate, and involve synthesis, isolation, and storage of an intermediate, new molecular entity (the conjugated mAb) whose biochemical properties can differ from those of the parent protein. To circumvent these issues, we developed a photoradiochemical approach that uses fast, chemoselective, light‐induced protein modification under mild conditions with novel metal‐ion‐binding chelates derivatised with aryl azide (ArN3) groups. Experiments show that one‐pot photochemical conjugation and radiolabelling of formulated mAbs can be achieved in <20 min.

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Additional indexing

Item Type:Journal Article, refereed, further contribution
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Scopus Subject Areas:Physical Sciences > Catalysis
Physical Sciences > General Chemistry
Language:English
Date:11 February 2019
Deposited On:25 Apr 2019 06:26
Last Modified:05 Dec 2020 01:00
Publisher:Wiley-VCH Verlag
ISSN:1433-7851
OA Status:Green
Publisher DOI:https://doi.org/10.1002/anie.201813287
Project Information:
  • : FunderSNSF
  • : Grant IDPP00P2_163683
  • : Project TitleAdvanced radiochemical methods for multi-modal imaging with nanomedicines
  • : FunderH2020
  • : Grant ID676904
  • : Project TitleDeveloping multi-modality nanomedicines for targeted annotation of oncogenic signaling pathways
  • : FunderKrebsliga
  • : Grant IDKLS‐4257‐08‐2017
  • : Project Title

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