Imaging of molecular target modulation in oncology: challenges of early clinical trials

The development of molecularly targeted anticancer therapies has resulted in a paradigm shift in the clinical drug development process. Phase 1 studies now routinely incorporate pharmacodynamic biomarker end-points, specifically to evaluate whether a targeted therapy has the desired impact on its target and whether this leads to clinical benefit. Non-invasive molecular imaging using positron emission tomography (PET) has shown promise in this setting, in particular where target modulation directly impacts on glucose metabolism or cell proliferation. In this review, we discuss the challenges in identifying PET biomarkers of target modulation by a novel targeted therapy in the preclinical setting and in their translation into the clinical setting.