Background
Non-invasive imaging biomarkers of cellular proliferation hold great promise for quantifying response to personalized medicine in oncology. An emerging approach to assess tumor proliferation utilizes the positron emission tomography (PET) tracer 3'-deoxy-3'[(18)F]-fluorothymidine, [(18)F]-FLT. Though several studies have associated serial changes in [(18)F]-FLT-PET with elements of therapeutic response, the degree to which [(18)F]-FLT-PET quantitatively reflects proliferative index has been continuously debated for more that a decade. The goal of this study was to elucidate quantitative relationships between [(18)F]-FLT-PET and cellular metrics of proliferation in treatment naïve human cell line xenografts commonly employed in cancer research.
Conclusions
Our findings illustrate that [(18)F]-FLT-PET reflects tumor proliferation as a function of thymidine salvage pathway utilization. Unlike more general proliferation markers, such as Ki67, [(18)F]-FLT PET reflects proliferative indices to variable and potentially unreliable extents. [(18)F]-FLT-PET cannot discriminate moderately proliferative, thymidine salvage-driven tumors from those of high proliferative index that rely primarily upon de novo thymidine synthesis. Accordingly, the magnitude of [(18)F]-FLT uptake should not be considered a surrogate of proliferative index. These data rationalize the diversity of [(18)F]-FLT-PET correlative results previously reported and suggest future best-practices when [(18)F]-FLT-PET is employed in oncology.