Anatomical, functional and molecular characteristics can be used as imaging biomarkers. In cancer treatment, CT (or MRI) measurements of changes of tumor volume are based on the “Response evaluation Criteria in Solid Tumours” (RECIST) criteria . These anatomical biomarkers are the only imaging surrogate endpoints that are accepted in cancer treatment. However, these anatomical biomarkers are suboptimal to assess the effect of some targeted treatments that do not cause regression of tumor volume, but rather increase in the extent of tumor necrosis .
A lot of functional biomarkers obtained with several imaging methods, including PET, contrast-enhanced CT, perfusion CT and MRI, diffusion-weighted MRI, MR elastography and spectroscopy, have the potential to complement or even replace the RECIST criteria. However, important efforts of qualification and standardization remain to be done before the acceptance of some of these functional biomarkers as surrogate endpoints. 18F-FDG-PET may serve as an illustrative example. In clinical routine, 18F-FDG-PET is increasingly used to assess the response to treatment in tumor patients. However, 18F-FDG-PET as an imaging biomarker has not yet been sufficiently validated to be accepted as a surrogate endpoint for clinical studies by regulatory agencies. Currently, a multi-centre qualification study of 18F-FDG-PET/CT as a predictive marker of tumor response and patient outcome in patients with non-small cell lung cancer has been initiated by the American College of Radiology Imaging Network (ACRIN).
Functional imaging biomarkers are increasingly used as pharmacodynamic biomarkers. Relative to molecular imaging biomarkers, which are target-specific, functional imaging biomarkers have the advantage of being downstream markers that probe general capabilities of disease, including cell death, proliferation, glycolysis, hypoxia, tumor invasiveness, angiogenesis, inflammation and fibrosis. Although a lot of functional imaging biomarkers have been proposed as pharmacodynamic biomarkers in early drug development, most of these biomarkers need further validation and standardization for their qualification in phase 1 and 2 human studies.