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

Mol Imaging Biol. 2018 Apr;20(2):194-199. doi: 10.1007/s11307-017-1125-3.

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.

Keywords: Oncology; PET; Thymidine phosphorylase; [18F]FLT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dideoxynucleosides / chemistry
  • Dideoxynucleosides / pharmacokinetics*
  • Humans
  • Mice
  • Neoplasms, Experimental / enzymology*
  • Thymidine / metabolism
  • Thymidine Phosphorylase / metabolism*

Substances

  • Dideoxynucleosides
  • Thymidine Phosphorylase
  • alovudine
  • Thymidine