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Simultaneous Photoradiochemical Labelling of Antibodies for Immuno-PET

50 Pages Posted: 29 Jan 2019 Sneak Peek Status: Review Complete

See all articles by Malay Patra

Malay Patra

University of Zurich - Department of Chemistry

Simon Klingler

University of Zurich - Department of Chemistry

Larissa S. Eichenberger

University of Zurich - Department of Chemistry

Jason Holland

University of Zurich - Department of Chemistry

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Abstract

A method for the simultaneous, one-step photochemical conjugation and 89Zr-radiolabelling of antibodies is introduced. A photoactivativable chelate based on the functionalisation of desferrioxamine B with an arylazide moiety (DFO-ArN3, [1]) was synthesised. The radiolabelled complex, 89Zr-1+ was produced and characterised. Density functional theory (DFT) calculations were used to investigate the mechanism of arylazide photoactivation. 89Zr-radiolabelling experiments were also used to determine the efficiency of photochemical conjugation. A standard two-step approach gave a measured conjugation efficiency of 3.50.4%. In contrast, the new one-step process gave a higher photoradiolabelling efficiency of ~76%. Stability measurements, cellular saturation binding assays, PET imaging and biodistribution studies in mice bearing SK-OV-3 tumours confirmed the biochemical viability and tumour specificity of photoradiolabelled [89Zr]ZrDFO-azepin-trastuzumab. Experimental data support the conclusion that the combination of photochemistry and radiochemistry is a viable strategy for producing radiolabelled proteins for imaging and therapy.

Suggested Citation

Patra, Malay and Klingler, Simon and Eichenberger, Larissa S. and Holland, Jason, Simultaneous Photoradiochemical Labelling of Antibodies for Immuno-PET (December 28, 2018). Available at SSRN: https://ssrn.com/abstract=3307531 or http://dx.doi.org/10.2139/ssrn.3307531
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Malay Patra

University of Zurich - Department of Chemistry

Winterthurerstrasse 190
Zurich, 8057
Switzerland

Simon Klingler

University of Zurich - Department of Chemistry

Winterthurerstrasse 190
Zurich, 8057
Switzerland

Larissa S. Eichenberger

University of Zurich - Department of Chemistry

Winterthurerstrasse 190
Zurich, 8057
Switzerland

Jason Holland (Contact Author)

University of Zurich - Department of Chemistry ( email )

Winterthurerstrasse 190
Zurich, 8057
Switzerland

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