6-3　Imaging of lymph nodes contributes to an assessment of relevance of macrophage accumulation observed for dalcetrapib in vitro and in vivo in animal studies

抄録

　The translation of non-clinical findings with potential safety impact on patients into the environment of clinical trials is often difficult. The availability of markers for toxicity recorded in animal studies is key for monitoring translation, onset and progression in the clinical context. Many more or less pronounced aspects of organ or tissue damage are hardly associated with any such reliable markers of toxicity. In this context, FDA’s Critical Path Initiative has reinforced the need for additional biomarkers to predict drug toxicity in preclinical studies, specifically biomarkers that can act as surrogate endpoints and/or aid in making efficacious and cost-saving decisions or terminating drug development more quickly¹⁾. In response to the Critical Path Initiative, in October 2006, a biomarker consortium including the FDA, the Foundation for the National Institutes of Health, and the Pharmaceutical Research and Manufacturers of America was launched, which focuses on developing biomarkers for use in regulatory decision making, as well as biomarker discovery²⁾. Such biomarkers are important for translational efficacy and safety and, in terms of safety, should ideally judge early an effect of organ function or constitution before severe damage sets in to facilitate treatment discontinuation in the clinical setting and to judge reversibility. Thus, safety biomarkers add profoundly on the risk-benefit evaluation of pharmaceuticals in clinical trials, for their approval for marketing and in later stages of a pharmaceutical in real world treatment conditions. In some cases, non-clinical efficacy or safety aspects are amenable to modern imaging techniques and thus their impact on the clinical development of a drug can be judged “online” with such techniques facilitating early readout of efficacy and safety. Among various imaging modalities, the imaging of lymph nodes in particular in the gastrointestinal (GI) tract of cancer patients has become an important clinical tool³⁾. Positron emission tomography (PET) nowadays has a high resolution and offers the possibility to derive even staging information for lymph node enlargement.