In:
European Journal of Haematology, Wiley, Vol. 77, No. 2 ( 2006-08), p. 102-108
Abstract:
Abstract: Background : In Hodgkin's lymphoma, F‐18‐fluoro‐deoxy‐ d ‐glucose positron emission tomography (FDG‐PET) is used for staging and response evaluation after chemotherapy. However, drug‐mediated downregulation of glucose uptake in viable Hodgkin's lymphoma cells might limit the use of FDG‐PET. Methods : We analyzed the effect of etoposide on cell viability and uptake of F‐18‐fluoro‐deoxy‐ d ‐glucose or the glucose analog 2‐[ N ‐(7‐nitrobenz‐2‐oxa‐1,3‐diazol‐4‐yl)amino]‐2‐deoxyglucose (2‐NBDG) in vitro . Results : Etoposide induced a dose‐dependent cytotoxicity in HDLM‐2 cells which was significantly correlated with reduced FDG uptake. However, it also significantly increased the portion of viable cells which did not take up 2‐NBDG. Interestingly, etoposide‐induced cytotoxicity was mainly mediated via caspase‐dependent mechanisms, whereas the cell death induced by deprivation of glucose was mediated via caspase‐independent mechanisms. Conclusion : Etoposide‐mediated reduction of glucose uptake by Hodgkin's lymphoma cells is mainly caused by cell death. In a small fraction of viable cells, etoposide might downregulate glucose transporters and/or hexokinase activity and by that inhibit glucose uptake. This, however, might not lead to false‐negative results of response evaluation in Hodgkin's lymphoma patients after chemotherapy, because inhibition of glucose uptake itself seems to be a strong inducer of cell death. Altogether, this study provides important in vitro evidence to clarify the mechanisms by which FDG‐PET monitors the effect of anti‐cancer treatment in Hodgkin's lymphoma patients.
Type of Medium:
Online Resource
ISSN:
0902-4441
,
1600-0609
DOI:
10.1111/ejh.2006.77.issue-2
DOI:
10.1111/j.1600-0609.2006.00675.x
Language:
English
Publisher:
Wiley
Publication Date:
2006
detail.hit.zdb_id:
2027114-1
