Despite breath-taking technological progress, modern pharmaceutical industry suffers from high attrition rates. In fact, only one in twenty lead compounds identified in non-clinical development passes through clinical trials and to market. The unacceptably low predictive power of many preclinical models stems, in part, from the lack of relevance and/or poor resolution of imaging techniques employed in drug development. Thus, in vivo imaging typically does not yield sufficient spatial resolution, whereas in vitro microscopy methods lack pathophysiological relevance. At present, only the in vivo two-photon microscopy (IV2PM) combines the crucial advantages of both imaging and microscopy, as it introduces the nanometer-scale spatial resolution of in vitro microscopy into the highly relevant context of in vivo imaging. In the present concise review, we discuss the most exciting applications of this game-changing technique in academic research of the past decade, and provide an outlook on the future role of IV2PM in drug discovery and development.Non peer reviewe
