Molecular Imaging and Biology

, Volume 20, Issue 2, pp 194–199 | Cite as

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

  • Sonja Schelhaas
  • Kathrin Heinzmann
  • Davina J. Honess
  • Donna-Michelle Smith
  • Heather Keen
  • Sandra Heskamp
  • Timothy H. Witney
  • Laurent Besret
  • Sabrina Doblas
  • John R. Griffiths
  • Eric O. Aboagye
  • Andreas H. Jacobs
Brief Article
  • 143 Downloads

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.

Key words

[18F]FLT PET Thymidine phosphorylase Oncology 

Notes

Funding Information

The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking (www.imi.europa.eu) under grant agreement number 115151, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution. This work was also supported by the Deutsche Forschungsgemeinschaft (DFG), Cells-in-Motion Cluster of Excellence (EXC1003-CiM), University of Münster, and the Interdisciplinary Centre for Clinical Research (IZKF, core unit PIX), Münster, Germany.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All applicable institutional and national guidelines for the care and use of animals were followed.

Supplementary material

11307_2017_1125_MOESM1_ESM.pdf (400 kb)
ESM 1 (PDF 400 kb)

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Copyright information

© World Molecular Imaging Society 2017

Authors and Affiliations

  • Sonja Schelhaas
    • 1
  • Kathrin Heinzmann
    • 2
    • 3
  • Davina J. Honess
    • 2
  • Donna-Michelle Smith
    • 2
  • Heather Keen
    • 4
  • Sandra Heskamp
    • 5
  • Timothy H. Witney
    • 3
    • 6
  • Laurent Besret
    • 7
  • Sabrina Doblas
    • 8
  • John R. Griffiths
    • 2
  • Eric O. Aboagye
    • 3
  • Andreas H. Jacobs
    • 1
    • 9
  1. 1.European Institute for Molecular Imaging (EIMI)Westfälische Wilhelms-Universität (WWU) MünsterMünsterGermany
  2. 2.Cancer Research UK Cambridge InstituteUniversity of CambridgeCambridgeUK
  3. 3.Comprehensive Cancer Imaging CentreImperial College LondonLondonUK
  4. 4.PHB Imaging GroupAstraZenecaMacclesfieldUK
  5. 5.Department of Radiology and Nuclear MedicineRadboud University Medical CentreNijmegenThe Netherlands
  6. 6.UCL Centre for Advanced Biomedical ImagingUniversity College LondonLondonUK
  7. 7.Sanofi OncologyVitry-sur-SeineFrance
  8. 8.LBI, UMR1149-CRIINSERMParisFrance
  9. 9.Department of Geriatric MedicineJohanniter HospitalBonnGermany

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