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Simultaneous Photoradiochemical Labeling of Antibodies for Immuno-Positron Emission Tomography

Patra, Malay; Klingler, Simon; Eichenberger, Larissa S; Holland, Jason P (2019). Simultaneous Photoradiochemical Labeling of Antibodies for Immuno-Positron Emission Tomography. iScience, 13:416-431.

Abstract

A method for the simultaneous (one-step) photochemical conjugation and 89Zr-radiolabeling of antibodies is introduced. A photoactivatable chelate based on the functionalization of desferrioxamine B with an arylazide moiety (DFO-ArN3, [1]) was synthesized. The radiolabeled complex, 89Zr-1+, was produced and characterized. Density functional theory calculations were used to investigate the mechanism of arylazide photoactivation. 89Zr-radiolabeling experiments were also used to determine the efficiency of photochemical conjugation. A standard two-step approach gave a measured conjugation efficiency of 3.5% ± 0.4%. In contrast, the one-step process gave a higher photoradiolabeling efficiency of ∼76%. Stability measurements, cellular saturation binding assays, positron emission tomographic imaging, and biodistribution studies in mice bearing SK-OV-3 tumors confirmed the biochemical viability and tumor specificity of photoradiolabeled [89Zr]ZrDFO-azepin-trastuzumab. Experimental data support the conclusion that the combination of photochemistry and radiochemistry is a viable strategy for producing radiolabeled proteins for imaging and therapy.

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Scopus Subject Areas:Health Sciences > Multidisciplinary
Language:English
Date:1 March 2019
Deposited On:24 Apr 2019 13:58
Last Modified:21 Oct 2024 01:38
Publisher:Cell Press (Elsevier)
ISSN:2589-0042
OA Status:Gold
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.isci.2019.03.004
Project Information:
  • Funder: SNSF
  • Grant ID: PP00P2_163683
  • Project Title: Advanced radiochemical methods for multi-modal imaging with nanomedicines
  • Funder: H2020
  • Grant ID: 676904
  • Project Title: NanoSCAN - Developing multi-modality nanomedicines for targeted annotation of oncogenic signaling pathways
  • Funder: Krebsliga
  • Grant ID: KLS-4257-08-2017
  • Project Title:
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  • Licence: Creative Commons: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)

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