3′-Deoxy-3′-[18F]Fluorothymidine Uptake Is Related to Thymidine Phosphorylase Expression in Various Experimental Tumor Models

S. Schelhaas; K. Heinzmann; D.J. Honess; D.-M. Smith; H. Keen; S. Heskamp; T.H. Witney; L. Besret; S. Doblas; J.R. Griffiths; E.O. Aboagye; A.H. Jacobs

doi:10.1007/s11307-017-1125-3

3′-Deoxy-3′-[18F]Fluorothymidine Uptake Is Related to Thymidine Phosphorylase Expression in Various Experimental Tumor Models

S. Schelhaas, K. Heinzmann, D.J. Honess, D.-M. Smith, H. Keen, S. Heskamp, T.H. Witney, L. Besret, S. Doblas, J.R. Griffiths, E.O. Aboagye, A.H. Jacobs

Imaging Chemistry & Biology

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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.

Original language	English
Pages (from-to)	194-199
Number of pages	6
Journal	MOLECULAR IMAGING AND BIOLOGY
Volume	20
Issue number	2
DOIs	https://doi.org/10.1007/s11307-017-1125-3
Publication status	Published - 20 Apr 2018

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Schelhaas, S., Heinzmann, K., Honess, D. J., Smith, D.-M., Keen, H., Heskamp, S., Witney, T. H., Besret, L., Doblas, S., Griffiths, J. R., Aboagye, E. O., & Jacobs, A. H. (2018). 3′-Deoxy-3′-[18F]Fluorothymidine Uptake Is Related to Thymidine Phosphorylase Expression in Various Experimental Tumor Models. MOLECULAR IMAGING AND BIOLOGY, 20(2), 194-199. https://doi.org/10.1007/s11307-017-1125-3

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title = "3′-Deoxy-3′-[18F]Fluorothymidine Uptake Is Related to Thymidine Phosphorylase Expression in Various Experimental Tumor Models",

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.",

author = "S. Schelhaas and K. Heinzmann and D.J. Honess and D.-M. Smith and H. Keen and S. Heskamp and T.H. Witney and L. Besret and S. Doblas and J.R. Griffiths and E.O. Aboagye and A.H. Jacobs",

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Schelhaas, S, Heinzmann, K, Honess, DJ, Smith, D-M, Keen, H, Heskamp, S, Witney, TH, Besret, L, Doblas, S, Griffiths, JR, Aboagye, EO & Jacobs, AH 2018, '3′-Deoxy-3′-[18F]Fluorothymidine Uptake Is Related to Thymidine Phosphorylase Expression in Various Experimental Tumor Models', MOLECULAR IMAGING AND BIOLOGY, vol. 20, no. 2, pp. 194-199. https://doi.org/10.1007/s11307-017-1125-3

TY - JOUR

T1 - 3′-Deoxy-3′-[18F]Fluorothymidine Uptake Is Related to Thymidine Phosphorylase Expression in Various Experimental Tumor Models

AU - Schelhaas, S.

AU - Heinzmann, K.

AU - Honess, D.J.

AU - Smith, D.-M.

AU - Keen, H.

AU - Heskamp, S.

AU - Witney, T.H.

AU - Besret, L.

AU - Doblas, S.

AU - Griffiths, J.R.

AU - Aboagye, E.O.

AU - Jacobs, A.H.

N1 - Export Date: 14 November 2018

PY - 2018/4/20

Y1 - 2018/4/20

N2 - 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.

AB - 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.

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DO - 10.1007/s11307-017-1125-3

M3 - Article

SN - 1536-1632

VL - 20

SP - 194

EP - 199

JO - MOLECULAR IMAGING AND BIOLOGY

JF - MOLECULAR IMAGING AND BIOLOGY

IS - 2

ER -

3′-Deoxy-3′-[18F]Fluorothymidine Uptake Is Related to Thymidine Phosphorylase Expression in Various Experimental Tumor Models

Abstract

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