July 2014 - Article in Chem. Comm. Published

Helen's paper on 68Ga-pre-targeting of the antibody Cetuximab to allow PET imaging of colorectal, head and neck cancers is published

Helen L. Evans, Quang-Dé Nguyen, Laurence S. Carroll, Frazer J. Twyman, Alan C. Spivey, and Eric O. Aboagye, 'Rapid Bioorthogonal ⁶⁸Ga-labeling of Cetuximab for Selective EGFR Imaging' Chem. Commun. 2014, ASAP DOI.

A fast and efficient method for radiolabeling clinically relevant monoclonal antibodies (mAbs) remains subject of intense investigation, due to the prospect this holds for imaging with high specificity their corresponding targets. Notably, a number of studies have been conducted into the development of Positron Emission Tomography (PET) imaging agents that selectively target the epidermal growth factor receptor EGFR/ErbB1. Bioorthogonal Inverse-electron-Demand Diels-Alder (IeDDA) reactions between 1,2,4,5-tetrazines and highly strained alkenes exhibit remarkable kinetics in aqueous media in comparison to other ’click’-type reactions such as the strain-promoted alkyne-azide cycloaddition (SPAAC),  whilst maintaining impressive biocompatibility. These reactions additionally benefit from having readily available reactive partners; the tetrazine and dienophile reaction partners may both be synthesized and functionalized for the appropriate application in a few steps. Herein, we describe a fast and robust method for achieving ⁶⁸Ga-labeling of the EGFR-selective Cetuximab mAb using the IeDDA reaction, and the subsequent non-invasive imaging of EGFR in vivo, highlighting the attractiveness and potential versatility of this approach over traditional methods of mAb labeling. Additionally, initial experiments into a two-step in vivo pretargeting strategy are demonstrated, suggesting the utility of this strategy within a multistep pretargeting context.