TY - JOUR
T1 - The uptake of 3'-deoxy-3'-[(18)F]fluorothymidine into L5178Y tumours in vivo is dependent on thymidine kinase 1 protein levels.
AU - Barthel, H
AU - Perumal, M
AU - Latigo, J
AU - He, Q
AU - Brady, F
AU - Luthra, SK
AU - Price, PM
AU - Aboagye, EO.
PY - 2005
Y1 - 2005
N2 - PURPOSE. The aim of this study was to investigate the role of thymidine kinase 1 (TK(1)) protein in 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) positron emission tomography (PET) studies. METHODS. We investigated the in vivo kinetics of [(18)F]FLT in TK(1)+/- and TK(1)-/- L5178Y mouse lymphoma tumours that express different levels of TK(1) protein. RESULTS. [(18)F]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 TK(1)+/- 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 [(18)F]FLT uptake for the TK(1)+/- 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 [(18)F]FLT uptake were in keeping with a 48% higher TK(1) protein in the TK(1)+/- 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 [(18)F]FLT accumulation and TK(1) 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 [(18)F]FLT kinetics depend on TK(1) protein expression. ATP may be important in realising this effect. Thus, [(18)F]FLT-PET has the potential to yield specific information on tumour proliferation in diagnostic imaging and therapy monitoring.
AB - PURPOSE. The aim of this study was to investigate the role of thymidine kinase 1 (TK(1)) protein in 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) positron emission tomography (PET) studies. METHODS. We investigated the in vivo kinetics of [(18)F]FLT in TK(1)+/- and TK(1)-/- L5178Y mouse lymphoma tumours that express different levels of TK(1) protein. RESULTS. [(18)F]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 TK(1)+/- 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 [(18)F]FLT uptake for the TK(1)+/- 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 [(18)F]FLT uptake were in keeping with a 48% higher TK(1) protein in the TK(1)+/- 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 [(18)F]FLT accumulation and TK(1) 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 [(18)F]FLT kinetics depend on TK(1) protein expression. ATP may be important in realising this effect. Thus, [(18)F]FLT-PET has the potential to yield specific information on tumour proliferation in diagnostic imaging and therapy monitoring.
M3 - Article
SN - 1619-7089
JO - Eur J Nucl Med Mol Imaging
JF - Eur J Nucl Med Mol Imaging
ER -