» Articles » PMID: 28971330

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

Overview
Publisher Springer
Date 2017 Oct 4
PMID 28971330
Citations 2
Authors
Affiliations
Soon will be listed here.
Abstract

Purpose: We recently reported that high thymidine phosphorylase (TP) expression is accompanied by low tumor thymidine concentration and high 3'-deoxy-3'-[F]fluorothymidine ([F]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 [F]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 [F]FLT SUV (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, [F]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 [F]FLT uptake.

Citing Articles

F-FLT PET/CT as a Prognostic Imaging Biomarker of Disease-Specific Survival in Patients with Primary Soft-Tissue Sarcoma.

Crompton J, Armstrong W, Eckardt M, Seyedroudbari A, Tap W, Dry S J Nucl Med. 2021; 63(5):708-712.

PMID: 34593596 PMC: 9051595. DOI: 10.2967/jnumed.121.262502.


Exploring Solvent Effects in the Radiosynthesis of F-Labeled Thymidine Analogues toward Clinical Translation for Positron Emission Tomography Imaging.

Li J, Van Valkenburgh J, Conti P, Chen K ACS Pharmacol Transl Sci. 2021; 4(1):266-275.

PMID: 33615178 PMC: 7887844. DOI: 10.1021/acsptsci.0c00184.

References
1.
Leyton J, Smith G, Lees M, Perumal M, Nguyen Q, Aigbirhio F . Noninvasive imaging of cell proliferation following mitogenic extracellular kinase inhibition by PD0325901. Mol Cancer Ther. 2008; 7(9):3112-21. DOI: 10.1158/1535-7163.MCT-08-0264. View

2.
Heinzmann K, Honess D, Lewis D, Smith D, Cawthorne C, Keen H . The relationship between endogenous thymidine concentrations and [(18)F]FLT uptake in a range of preclinical tumour models. EJNMMI Res. 2016; 6(1):63. PMC: 4980847. DOI: 10.1186/s13550-016-0218-3. View

3.
Schelhaas S, Heinzmann K, Bollineni V, Kramer G, Liu Y, Waterton J . Preclinical Applications of 3'-Deoxy-3'-[F]Fluorothymidine in Oncology - A Systematic Review. Theranostics. 2017; 7(1):40-50. PMC: 5196884. DOI: 10.7150/thno.16676. View

4.
Li K, Rivory L, Clarke S . Rapid quantitation of plasma 2'-deoxyuridine by high-performance liquid chromatography/atmospheric pressure chemical ionization mass spectrometry and its application to pharmacodynamic studies in cancer patients. J Chromatogr B Analyt Technol Biomed Life Sci. 2005; 820(1):121-30. DOI: 10.1016/j.jchromb.2005.03.008. View

5.
Barthel H, Perumal M, Latigo J, He Q, Brady F, Luthra S . The uptake of 3'-deoxy-3'-[18F]fluorothymidine into L5178Y tumours in vivo is dependent on thymidine kinase 1 protein levels. Eur J Nucl Med Mol Imaging. 2005; 32(3):257-63. DOI: 10.1007/s00259-004-1611-0. View