Abstract

Abstract Over 180 chemically distinct cancer drugs are currently in clinical use while new nanomaterials, small molecule inhibitors and newer immunotherapeutics are entering clinical trials. Preclinical testing usually involves measuring tumor sizes, survival endpoints, the use of histopathology and measurement of serum biomarkers. Yet, despite all of these advances, preciously little is known on how many of these compounds actually work (or fail) at the single cell level in vivo, what the spatial and temporal heterogeneity is and how efficacy can be improved. The latter is particularly vexing as the majority of patients show suboptimal responses and tumors often relapse within months-years. With the recent development of i) single cell in vivo imaging technology (Nat Commun 2013;4,1504), ii) fluorescent nanoparticles and encapsulated therapeutics (Science Transl Med, 2015;7:314; Nat Commun. 2015;6:8692), iii) in vivo reporters of host response, cell death or DNA damage (ChemMedChem, 2014;9:1131), iv) new computational analysis (Nat Methods, 2015;12:577), and v) armed with new biological insight from feasibility studies we are now able to address important cancer therapeutics questions in ways that were not previously possible. In this presentation I will review imaging approaches for the functional assessment of new therapeutics at the single cell level in vivo, addressing key questions on distribution (pharmacokinetics, PK) and specific cellular response (pharmacodynamics, PD). Citation Format: Ralph Weissleder. Imaging drug delivery and nanotherapeutics. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr IA13.

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