Disproportional increase in thymidine uptake relative to tumor cell proliferation in indolent NHLs indicates enhanced DNA repair

Objectives Uptake of radiolabeled thymidine (td) or td analogs is used to assess tumor cell proliferation as well as tumor DNA repair synthesis after inhibition of proliferation with certain drugs. We evaluated whether the relationship between td uptake and tumor cell proliferation is different in indolent vs. aggressive NHLs.

Methods 24 patients (pts) with histologically-confirmed aggressive (n=17) or indolent NHLs (n=7) underwent pretherapy imaging with ¹⁸F-fluorothymidine (FLT) and biopsy to determine the proliferative cell fraction by Ki-67 index. Tumoral FLT uptake was determined by maximum standardized uptake values (SUVmax) and FLT-SUV to Ki-67 ratio calculated in all pts.

Results Disproportional increase in FLT-SUVmax relative to tumor cell proliferation was found in indolent NHLs: median %Ki-67 was 5% in indolent vs. 80% in aggressive NHL whereas median FLT-SUVmax was 3.6 vs. 9.4. Disproportional increase in FLT-SUV in indolent NHLs could not be explained by nonspecific FLT uptake in tumor extracellular space estimated to account for <0.2 SUV unit. Difference in the ratio of FLT-SUVmax to Ki-67 index between indolent and aggressive NHLs was highly significant (1.21 ± 0.77 vs. 0.18± 0.20; P=0.006).

Conclusions Disproportional increase in td uptake relative to %proliferating tumor cells in indolent NHLs probably reflects enhanced DNA repair in quiescent cells and might explain the general chemoresistance of these tumors. This observation could have important implications with respect to treatment of indolent NHLs.