Abstract
BackgroundWe 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).MethodsWe 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.Results18 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.ConclusionsThis 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 repair-related 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.
Highlights
We observed a disproportional 18 F-fluorothymidine (F-FLT) uptake in follicular lymphoma (FL)relative to its low cell proliferation
F-FLT-SUVmax to percentage of MIB-1 positive cells was significantly higher in FL compared with diffuse large B cell lymphoma (DLBCL)
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 Conclusions: This is the first demonstration of a striking discordance between 18 F-FLT uptake in FL and tumour cell proliferation
Summary
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 contributes to 18 F-FLT uptake in diffuse large B cell lymphoma (DLBCL). 18 F-fluorothymidine (18 F-FLT), a thymidine analogue, has been tested for its ability to measured tumour proliferative activity [3]. F-FLT uptake is determined by thymidine kinase-I (TK-1) activity, an enzyme closely linked to DNA synthesis and, indirectly to tumour cell proliferation [4]. Both can be imaged by PET, using either 18 F-FDG or 18 F-FLT. A close correlation was reported between 18 F-FLT uptake and the proliferation fraction in a mixed population of patients with FL and DLBCLs [5]
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