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by John W. Waterton on behalf of the TRISTAN Consortium

EMIM 2024

Abstract

Imaging metrics ("biomarkers"[1]) have a prominent role in predicting and detecting treatment benefit, for example as pharmacodynamic biomarkers or as companion diagnostics. However, all treatments involve risk of harm as well as possible benefit, so imaging biomarkers of harm or risk of harm (so-called "safety" biomarkers) are of equal or greater value than imaging biomarkers of treatment efficacy.
Imaging biomarkers of safety can be used in several ways. In toxicology studies in animals they can identify toxicity, determine therapeutic margin, or evaluate reversibility. In human trials, they can be used to halt dose escalation before overt toxicity, to characterise rare adverse events, or to evaluate reversibility. More generally, imaging biomarkers of safety can be used to monitor patients at risk of harm, so that treatment can be adjusted, or to deny particular treatments to patient at risk of harm from that treatment.
The development, validation and deployment of such biomarkers poses unique challenges. While efficacy biomarkers can easily be investigated in patients who elect to receive beneficial therapies, it is often ethically difficult or impossible to deliberately expose human subjects to harmful therapies. Moreover, to prepare for the case of rare and sporadic adverse events, the biomarker needs to be reproducibly available in any hospital in the world where the biomarker might be needed.
Imaging biomarkers of safety are particularly prominent in oncology, in Alzheimer's research, in neurology and rheumatology[2]. This work[3] aims to discover and develop imaging safety biomarkers addressing: harmful changes in liver transporter fluxes, maldistribution (with potentially harmful consequences) of biologic therapies, and drug-induced interstitial lung disease.