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.