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

2.50
Hdl Handle:
http://hdl.handle.net/10541/75883
Title:
The uptake of 3'-deoxy-3'-[18F]fluorothymidine into L5178Y tumours in vivo is dependent on thymidine kinase 1 protein levels.
Authors:
Barthel, Henryk; Perumal, Meg; Latigo, John; He, Qimin; Brady, Frank; Luthra, Sajinder K; Price, Patricia M; Aboagye, E O
Abstract:
PURPOSE: 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.
Affiliation:
Molecular Therapy and PET Oncology Research Group, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London, W12 0NN, UK.
Citation:
The 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
Journal:
European Journal of Nuclear Medicine and Molecular Imaging
Issue Date:
Mar-2005
URI:
http://hdl.handle.net/10541/75883
DOI:
10.1007/s00259-004-1611-0
PubMed ID:
15791434
Type:
Article
Language:
en
ISSN:
1619-7070
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorBarthel, Henryk-
dc.contributor.authorPerumal, Meg-
dc.contributor.authorLatigo, John-
dc.contributor.authorHe, Qimin-
dc.contributor.authorBrady, Frank-
dc.contributor.authorLuthra, Sajinder K-
dc.contributor.authorPrice, Patricia M-
dc.contributor.authorAboagye, E O-
dc.date.accessioned2009-07-29T14:21:38Z-
dc.date.available2009-07-29T14:21:38Z-
dc.date.issued2005-03-
dc.identifier.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. Imagingen
dc.identifier.issn1619-7070-
dc.identifier.pmid15791434-
dc.identifier.doi10.1007/s00259-004-1611-0-
dc.identifier.urihttp://hdl.handle.net/10541/75883-
dc.description.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.en
dc.language.isoenen
dc.subjectTumour Markersen
dc.subject.meshAnimals-
dc.subject.meshDideoxynucleosides-
dc.subject.meshLymphoma-
dc.subject.meshMale-
dc.subject.meshMetabolic Clearance Rate-
dc.subject.meshMice-
dc.subject.meshOrgan Specificity-
dc.subject.meshRadiopharmaceuticals-
dc.subject.meshThymidine Kinase-
dc.subject.meshTissue Distribution-
dc.subject.meshTumor Markers, Biological-
dc.titleThe uptake of 3'-deoxy-3'-[18F]fluorothymidine into L5178Y tumours in vivo is dependent on thymidine kinase 1 protein levels.en
dc.typeArticleen
dc.contributor.departmentMolecular Therapy and PET Oncology Research Group, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London, W12 0NN, UK.en
dc.identifier.journalEuropean Journal of Nuclear Medicine and Molecular Imagingen

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