Development of drug screening system with nanoimprinting 3D culture to provide effective drugs in vivo and the accompanying PET probes for therapy monitoring

Anti-cancer drug development typically utilizes high-throughput screening with two-dimensional (2D) cell culture. However, 2D culture induces cellular characteristics different from tumours in vivo, resulting in inefficient drug development. In this study, we developed an innovative high-throughput screening system using nanoimprinting 3D culture to simulate in vivo conditions, thereby accurately predicting effective drugs in vivo and the accompanying PET probes for therapy monitoring. Methods: HT29 cells were cultured in 3D using nano-culture plates (NCPs) (96-wells, SCIVAX), in which nanoscale square grid patterns were printed on transparent synthetic-resinous bases with the nanoimprinting technique (Yoshii et al. 2011 Biomaterials). In vitro drug screening was performed with the SCADS inhibitor kit I, which contains vehicle control, 16 existing clinically-used antitumor agents, and 79 promising molecular targeted drugs against cancer. In vivo therapeutic effect of the drugs selected by screening was tested using HT29 tumor-bearing mice. PET probe uptake after treatment with the selected drug was also tested with 3D culture and tumor-bearing mice, using 2-fluoro-2-deoxy-D-glucose (FDG), methionine, acetic acid, 3\u27-fluoro 3\u27-deoxythymidine (FLT), and 4\u27-thiothymidine (4-DST). Results: Nanoimprinting 3D screening more efficiently selected drugs that effectively inhibited cancer growth in vivo as compared to conventional 2D culture. Pattern of PET probe uptake after treatment in 3D culture was similar to that in in vivo tumors. Conclusions: Nanoimprinting 3D screening can be a useful tool to efficiently select effective drugs and the accompanying PET probes, which would accelerate drug development and help to propose suitable therapy monitoring method.The Society of Nuclear Medicine (SNM) annual meeting 201