Abstract
1480
Objectives: Tumor uptake of FLT is assumed to reflect proliferation while uptake of Choline and FDG represents metabolism. This study compares uptake of these radiopharmaceuticals in tumor cell lines to evaluate use for monitoring antimetabolic treatment. Methods: 10 tumor cell lines (NSCLC, esophagus, ovarian [n=3], breast, colon, thyroid, pancreas, hepatoma) were cultivated at subconfluent density for 48 h. The cells were treated with 5-FU for 4 h to identify drug doses inducing 50% reduction of clonogenic survival. After 24 h recovery, cultures were incubated with 18.5 kBq of 3-H-FLT, 3-H-FDG or 3-H-Choline and accumulated activity was measured on a liquid scintillation counter. Data were normalized for the number of surviving cells and the entire cell population. To test for differences between treated and untreated cells analysis of variance was applied. Results: Treatment with 5-FU reduced clonogenic survival in a dose-dependent manner in all tumor cell lines (IC50: 0.03 to 0.55 µM). In 7/10 entities FLT uptake increased after treatment by 1.2 to 4-fold per entire cell population or up to 5.5-fold per viable tumor cells, respectively. Only 2/10 cell lines exhibited reduced FLT uptake (65 and 30% of controls) as would be expected due to inhibited proliferation. In contrast FDG uptake per culture was significantly reduced in all treated cell lines. With Choline uptake of radiopharmaceutical was more moderately reduced reaching significance in 7/10 cases. At a cellular level though, some entities showed an increase of Choline and even a slight increase of FDG uptake after treatment. However, due to reduced cellularity the total radionuclide uptake per population never exceeded control levels. The strong increase of FLT accumulation after treatment is thus not considered as due to toxic stress reaction of cells. It can be explained by increased thymidine salvage following 5-FU induced blockade of Pyrimidine de-novo synthesis. Conclusions: Following antimetabolic treatment with 5-FU most tumor cell lines showed considerable increase of FLT but not of FDG or Choline uptake. In this situation FLT will be a measure of treatment induced thymidine salvage but will not reflect cell proliferation. FDG or Choline appear to be more suitable to monitor treatment response to 5-FU.
- Society of Nuclear Medicine, Inc.