Abstract #4790

Fluorothymidine as a Therapeutic Response Marker of the Investigational Anticancer Agent RAF265: Insights from 19F-NMR and Flow Cytometry

Andy Dzik-Jurasz¹, Melissa Lin², Kathleen Dohoney³, Jason McCormick⁴, Mary Ising⁴, Darrin Stuart⁵, Diana Jespersen⁴

¹Oncology Translational Medicine, Novartis Pharmaceuticals Corporation, Inc, Florham Park, NJ, United States; ²Novartis Pharmaceuticals Corporation, Inc, NJ, United States; ³Novartis Institutes for Biomedical Research, Inc, Cambridge, MA, United States; ⁴Oncology Translational Medicine, Novartis Pharmaceuticals Corporation, Inc, East Hanover, NJ, United States; ⁵Novartis Institutes for Biomedical Research, Inc, Emeryville, CA

Fluorothymidine is used as an index of cellular proliferation in studies of therapeutic response. We used 19F-NMR to follow signal changes in cell extracts of the melanoma cell line A375M incubated with 19F-fluorothymidine and the investigational anticancer agent RAF265. Flow cytometry was used to characterize differences in cell cycle profile, count and apoptosis. A 19F-resonance tentatively assigned to a phosphate metabolite of fluorothymidine demonstrated a lower intensity in the treatment group and flow cytometry reporting a drop in the proportion of metabolically active cells exposed to drug. This approach could be used to explore the cellular changes influencing fluorothymidine signal.