In vitro comparison of cell proliferation kinetics and uptake of tritiated fluorodeoxyglucose and L-methionine in squamous-cell carcinoma of the head and neck

Estimation of tumor proliferative activity is important for the optimal management of head and neck cancer. Noninvasive metabolic imaging with PET may complement currently used cytopathologic methods to study tumor proliferation. Methods: Fluoredeoxyglucose (FDG) and L-methionine (MET) were studied for their potential to assess in vitro the growth characteristics of three squamous-cell carcinoma (SCC) cell lines established recently in patients with head and neck cancer. A time-course uptake of tritiated FDG and MET was measured over the complete growth cycle of one rapidly growing (UT- SCC-5) and two relatively slower growing (UT-SCC-1A and UT-SCC-9) cell lines. DNA flow cytometry was used for assessment of proliferative activity. Results: There was a strong linear relationship for both FDG and MET uptake versus the viable cell number although absolute MET uptake was consistently lower than that of FDG in the exponential and plateau phases of growth (p < 0.01), leading MET to underestimate cell number. The pattern of MET uptake followed the flow cytometric changes in the proliferation index (% of S + G2/M cells) in two of three cases (UT-SCC-1A and UT-SCC-5) while a similar, although clearly weaker, relationship was seen with FDG and flow cytometry findings in only one case (UT-SCC-5). Conclusion: In these three human SCC cell lines assessed in vitro, FDG is a better marker of cell viability than MET, whereas MET is superior for estimating proliferative activity. Extrapolations of these in vitro data to the interpretation of PET images should be made with caution since tumors may have confounding factors that may affect in vivo tracer uptake.