The uptake of 3'-deoxy-3'-[18F]fluorothymidine into L5178Y tumours in vivo is dependent on thymidine kinase 1 protein levels.
Luthra, Sajinder K
Price, Patricia M
Aboagye, E O
AffiliationMolecular Therapy and PET Oncology Research Group, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London, W12 0NN, UK.
MetadataShow full item record
AbstractPURPOSE: The aim of this study was to investigate the role of thymidine kinase 1 (TK1) protein in 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT) positron emission tomography (PET) studies.METHODS: We investigated the in vivo kinetics of [18F]FLT in TK1+/- and TK1-/- L5178Y mouse lymphoma tumours that express different levels of TK1 protein.RESULTS: [18F]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 [18F]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 [18F]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 [18F]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 [18F]FLT kinetics depend on TK1 protein expression. ATP may be important in realising this effect. Thus, [18F]FLT-PET has the potential to yield specific information on tumour proliferation in diagnostic imaging and therapy monitoring.
CitationThe uptake of 3'-deoxy-3'-[18F]fluorothymidine into L5178Y tumours in vivo is dependent on thymidine kinase 1 protein levels. 2005, 32 (3):257-63 Eur. J. Nucl. Med. Mol. Imaging
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
- 3'-deoxy-3'-[18F]fluorothymidine as a new marker for monitoring tumor response to antiproliferative therapy in vivo with positron emission tomography.
- Authors: Barthel H, Cleij MC, Collingridge DR, Hutchinson OC, Osman S, He Q, Luthra SK, Brady F, Price PM, Aboagye EO
- Issue date: 2003 Jul 1
- In vivo biological activity of the histone deacetylase inhibitor LAQ824 is detectable with 3'-deoxy-3'-[18F]fluorothymidine positron emission tomography.
- Authors: Leyton J, Alao JP, Da Costa M, Stavropoulou AV, Latigo JR, Perumal M, Pillai R, He Q, Atadja P, Lam EW, Workman P, Vigushin DM, Aboagye EO
- Issue date: 2006 Aug 1
- Phosphorylation status of thymidine kinase 1 following antiproliferative drug treatment mediates 3'-deoxy-3'-[18F]-fluorothymidine cellular retention.
- Authors: Sala R, Nguyen QD, Patel CB, Mann D, Steinke JH, Vilar R, Aboagye EO
- Issue date: 2014
- Induction of thymidine kinase 1 after 5-fluorouracil as a mechanism for 3'-deoxy-3'-[18F]fluorothymidine flare.
- Authors: Lee SJ, Kim SY, Chung JH, Oh SJ, Ryu JS, Hong YS, Kim TW, Moon DH
- Issue date: 2010 Nov 15
- Positron emission tomography imaging of human colon cancer xenografts in mice with [18F]fluorothymidine after TAS-102 treatment.
- Authors: Lee HJ, Oh SJ, Lee EJ, Chung JH, Kim Y, Ryu JS, Kim SY, Lee SJ, Moon DH, Kim TW
- Issue date: 2015 May