18 F-fluorothymidine uptake in follicular lymphoma and error-prone DNA repair

Marielle J. Wondergem, Ken Herrmann, Sergei Syrbu, Josée M. Zijlstra, Nikie Hoetjes, Otto S. Hoekstra, Saskia A.G.M. Cillessen, Laura M. Moesbergen, Andreas K. Buck, Julie M. Vose, Malik E. Juweid

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1 Scopus citations

Abstract

Background: We observed a disproportional 18 F-fluorothymidine (F-FLT) uptake in follicular lymphoma (FL) relative to its low cell proliferation. We tested the hypothesis that the 'excess' uptake of 18 F-FLT in FL is related to error-prone DNA repair and investigated whether this also contributes to 18 F-FLT uptake in diffuse large B cell lymphoma (DLBCL). Methods: We performed immunohistochemical stainings to assess the pure DNA replication marker MIB-1 as well as markers of both DNA replication and repair like PCNA, TK-1 and RPA1 on lymph node biopsies of 27 FLs and 35 DLBCLs. In 7 FL and 15 DLBCL patients, 18 F-FLT-PET had been performed. Results: 18 F-FLT uptake was lower in FL than in DLBCL (median SUVmax 5.7 vs. 8.9, p = 0,004), but the ratio of 18 F-FLT-SUVmax to percentage of MIB-1 positive cells was significantly higher in FL compared with DLBCL (p = 0.001). The median percentage of MIB-1 positive cells was 10% (range, 10% to 20%) in FL and 70% (40% to 80%) in DLBCL. In contrast, the median percentages of PCNA, TK-1 and RPA1 positive cells were 90% (range, 80 to 100), 90% (80 to 100) and 100% (80 to 100) in FL versus 90% (60 to 100), 90% (60 to 100) and 100% (80 to 100) in DLBCL, respectively. Conclusions: This is the first demonstration of a striking discordance between 18 F-FLT uptake in FL and tumour cell proliferation. High expression of DNA replication and repair markers compared with the pure proliferation marker MIB-1 in FL suggests that this discordance might be due to error-prone DNA repair. While DNA repairrelated 18 F-FLT uptake considerably contributes to 18 F-FLT uptake in FL, its contribution to 18 F-FLT uptake in highly proliferative DLBCL is small. This apparently high contribution of DNA repair to the 18 F-FLT signal in FL may hamper studies where 18 F-FLT is used to assess response to cytostatic therapy or to distinguish between FL and transformed lymphoma.

Original languageEnglish (US)
Article number3
Pages (from-to)1-7
Number of pages7
JournalEJNMMI Research
Volume4
Issue number1
DOIs
StatePublished - 2014

Keywords

  • 18 F-fluorothymidine uptake
  • DNA repair
  • Follicular lymphoma
  • Non-hodgkin's lymphoma
  • Positron emission tomography

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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    Wondergem, M. J., Herrmann, K., Syrbu, S., Zijlstra, J. M., Hoetjes, N., Hoekstra, O. S., Cillessen, S. A. G. M., Moesbergen, L. M., Buck, A. K., Vose, J. M., & Juweid, M. E. (2014). 18 F-fluorothymidine uptake in follicular lymphoma and error-prone DNA repair. EJNMMI Research, 4(1), 1-7. [3]. https://doi.org/10.1186/2191-219X-4-3