PET imaging of DNA damage using 89Zr-labelled anti-γH2AX-TAT immunoconjugates


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James Knight1, Caitriona Topping1, Veerle Kersemans1, Nadia Falzone2, Nicola Sibson1, Bart Cornelissen1
1University of Oxford, Oxford, UK,2Institute for Cancer Research, Sutton, Surrey, UK

Abstract

Background

The efficacy of most anti-cancer treatments, including ionizing radiation (IR) and many cytotoxic drugs, depends on an ability to cause DNA damage. Previously, we showed that quantification of intra-tumoural DNA damage is possible, for example to predict early response to treatment. Using an 111In-labelled construct targeting DNA damage signalling protein via anti-γH2AX antibodies, linked to the cell-penetrating peptide, TAT, we demonstrated that SPECT imaging allows dose-dependent measurement of DNA double strand-breaks (1). Given the increasing availability of PET imaging in the clinic, we have now prepared a PET imaging agent, based on the same construct, radiolabelled with the positron-emitting isotope, 89Zr.