The uptake of 3′-deoxy-3′-[18F]fluorothymidine into L5178Y tumours in vivo is dependent on thymidine kinase 1 protein levels

Purpose: The aim of this study was to investigate the role of thymidine kinase 1 (TK1) protein in 3'-deoxy3'-[F-18]fluorothymidine ([F-18]FLT) positron emission tomography (PET) studies. Methods: We investigated the in vivo kinetics of [F-18]FLT in TK1+/- and TK1-/- L5178Y mouse lymphoma tumours that express different levels of TK1 protein. Results: [F-18]FLT-derived radioactivity, measured by a dedicated small animal PET scanner, increased within the tumours over 60 min. The area under the normalised tumour time-activity curve were significantly higher for the TK1+/- compared with the -/- variant (0.89 +/- 0.02 vs 0.79 +/- 0.03 MBq ml(-1) min, P = 0.043; n = 5 for each tumour type). Ex vivo gamma counting of tissues excised at 60 min p.i. (n = 8) also revealed significantly higher tumour [F-18]FLT uptake for the TK1+/- variant (6.2 +/- 0.6 vs 4.6 +/- 0.4% ID g(-1), P = 0.018). The observed differences between the cell lines with respect to [F-18]FLT uptake were in keeping with a 48% higher TK1 protein in the TK1+/- tumours versus the -/- variant (P = 0.043). On average, there were no differences in ATP levels between the two tumour variants (P = 1.00). A positive correlation between [F-18]FLT accumulation and TK1 protein levels (r = 0.68, P = 0.046) was seen. Normalisation of the data for ATP content further improved the correlation (r = 0.86, P = 0.003). Conclusion: This study shows that in vivo [F-18]FLT kinetics depend on TK1 protein expression. ATP may be important in realising this effect. Thus, [F-18]FLT-PET has the potential to yield specific information on tumour proliferation in diagnostic imaging and therapy monitoring.