Quantitative imaging biomarkers in the clinical development of targeted therapeutics: current and future perspectives

Targeted therapeutics have challenged how imaging techniques assess tumour response to treatment because many new agents are thought to cause cytostasis rather than cytotoxicity. Advanced tracer development, image acquisition, and image analysis have been used to produce quantitative biomarkers of pathophysiology, with particular focus on measurement of tumour vascular characteristics. Here, we critically appraise strategies available to generate imaging biomarkers for use in development of targeted therapeutics. We consider important practical and technical features of data acquisition and analysis because these factors determine the precise physiological meaning of every biomarker. We discuss the merits of volume-based and other size-based metrics for assessment of targeted therapeutics, and we examine the strengths and weaknesses of CT, MRI, and PET biomarkers derived from conventional clinical data. We review imaging biomarkers of tumour microvasculature and discuss imaging strategies that probe other physiological processes including cell proliferation, apoptosis, and tumour invasion. We conclude on the need to develop comprehensive compound-specific imaging biomarkers that are appropriate for every class of targeted therapeutics, and to investigate the complementary information given in multimodality imaging studies of targeted therapeutics.