Sonja Schelhaas1, Kathrin Heinzmann2,3, Davina J Honess2, Donna-Michelle Smith2, Heather Keen4, Sandra Heskamp5, Timothy H Witney3,6, Laurent Besret7, Sabrina Doblas8, John R Griffiths2, Eric O Aboagye3, Andreas H Jacobs9,10. 1. European Institute for Molecular Imaging (EIMI), Westfälische Wilhelms-Universität (WWU) Münster, Waldeyerstr. 15, 48149, Münster, Germany. 2. Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK. 3. Comprehensive Cancer Imaging Centre, Imperial College London, London, UK. 4. PHB Imaging Group, AstraZeneca, Alderley Park, Macclesfield, UK. 5. Department of Radiology and Nuclear Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands. 6. UCL Centre for Advanced Biomedical Imaging, University College London, London, UK. 7. Sanofi Oncology, Vitry-sur-Seine, France. 8. LBI, UMR1149-CRI, INSERM, Paris, France. 9. European Institute for Molecular Imaging (EIMI), Westfälische Wilhelms-Universität (WWU) Münster, Waldeyerstr. 15, 48149, Münster, Germany. ahjacobs@uni-muenster.de. 10. Department of Geriatric Medicine, Johanniter Hospital, Bonn, Germany. ahjacobs@uni-muenster.de.
Abstract
PURPOSE: We recently reported that high thymidine phosphorylase (TP) expression is accompanied by low tumor thymidine concentration and high 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT) uptake in four untreated lung cancer xenografts. Here, we investigated whether this relationship also holds true for a broader range of tumor models. PROCEDURES: Lysates from n = 15 different tumor models originating from n = 6 institutions were tested for TP and thymidylate synthase (TS) expression using western blots. Results were correlated to [18F]FLT accumulation in the tumors as determined by positron emission tomography (PET) measurements in the different institutions and to previously published thymidine concentrations. RESULTS: Expression of TP correlated positively with [18F]FLT SUVmax (ρ = 0.549, P < 0.05). Furthermore, tumors with high TP levels possessed lower levels of thymidine (ρ = - 0.939, P < 0.001). CONCLUSIONS: In a broad range of tumors, [18F]FLT uptake as measured by PET is substantially influenced by TP expression and tumor thymidine concentrations. These data strengthen the role of TP as factor confounding [18F]FLT uptake.
PURPOSE: We recently reported that high thymidine phosphorylase (TP) expression is accompanied by low tumorthymidine concentration and high 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT) uptake in four untreated lung cancer xenografts. Here, we investigated whether this relationship also holds true for a broader range of tumor models. PROCEDURES: Lysates from n = 15 different tumor models originating from n = 6 institutions were tested for TP and thymidylate synthase (TS) expression using western blots. Results were correlated to [18F]FLT accumulation in the tumors as determined by positron emission tomography (PET) measurements in the different institutions and to previously published thymidine concentrations. RESULTS: Expression of TP correlated positively with [18F]FLT SUVmax (ρ = 0.549, P < 0.05). Furthermore, tumors with high TP levels possessed lower levels of thymidine (ρ = - 0.939, P < 0.001). CONCLUSIONS: In a broad range of tumors, [18F]FLT uptake as measured by PET is substantially influenced by TP expression and tumorthymidine concentrations. These data strengthen the role of TP as factor confounding [18F]FLT uptake.
Authors: Aren van Waarde; David C P Cobben; Albert J H Suurmeijer; Bram Maas; Willem Vaalburg; Erik F J de Vries; Pieter L Jager; Harald J Hoekstra; Philip H Elsinga Journal: J Nucl Med Date: 2004-04 Impact factor: 10.057
Authors: P Workman; E O Aboagye; F Balkwill; A Balmain; G Bruder; D J Chaplin; J A Double; J Everitt; D A H Farningham; M J Glennie; L R Kelland; V Robinson; I J Stratford; G M Tozer; S Watson; S R Wedge; S A Eccles Journal: Br J Cancer Date: 2010-05-25 Impact factor: 7.640
Authors: Julius Leyton; Graham Smith; Mark Lees; Meg Perumal; Quang-de Nguyen; Franklin I Aigbirhio; Oksana Golovko; Quimin He; Paul Workman; Eric O Aboagye Journal: Mol Cancer Ther Date: 2008-09 Impact factor: 6.261
Authors: Henryk Barthel; Meg Perumal; John Latigo; Qimin He; Frank Brady; Sajinder K Luthra; Pat M Price; Eric O Aboagye Journal: Eur J Nucl Med Mol Imaging Date: 2004-09-04 Impact factor: 9.236
Authors: Sonja Schelhaas; Kathrin Heinzmann; Vikram R Bollineni; Gerbrand M Kramer; Yan Liu; John C Waterton; Eric O Aboagye; Anthony F Shields; Dmitry Soloviev; Andreas H Jacobs Journal: Theranostics Date: 2017-01-01 Impact factor: 11.556
Authors: Kathrin Heinzmann; Davina Jean Honess; David Yestin Lewis; Donna-Michelle Smith; Christopher Cawthorne; Heather Keen; Sandra Heskamp; Sonja Schelhaas; Timothy Howard Witney; Dmitry Soloviev; Kaye Janine Williams; Andreas Hans Jacobs; Eric Ofori Aboagye; John Richard Griffiths; Kevin Michael Brindle Journal: EJNMMI Res Date: 2016-08-11 Impact factor: 3.138
Authors: Joseph G Crompton; Wesley R Armstrong; Mark A Eckardt; Ameen Seyedroudbari; William D Tap; Sarah M Dry; Evan R Abt; Jeremie Calais; Ken Herrmann; Johannes Czernin; Fritz C Eilber; Matthias R Benz Journal: J Nucl Med Date: 2021-09-30 Impact factor: 11.082