Effect of corticosteroids on 18F-FDG uptake in tumor lesions after chemotherapy.
To be a reliable predictor of response, (18)F-FDG uptake should reflect changes in the amount of viable tumor cells. However, (18)F-FDG also accumulates in inflammatory cells. Shortly after treatment, the influx of inflammatory cells in the tumor can therefore interfere with early response evaluation. The aim of this study was to investigate whether this inflammation is suppressed by the administration of corticosteroids and, in turn, can improve the correlation of (18)F-FDG uptake with tumor cell kill.


METHODS
Severe combined immunodeficiency mice were inoculated subcutaneously with Daudi cells. When the tumor measured 15 mm, mice were divided in 2 groups treated with 1 single dose of cyclophosphamide, 125 mg/kg (group A) or cyclophosphamide followed by hydrocortisone (0.2 mg/d) for 5 d (group B). The change in (18)F-FDG uptake was evaluated with small-animal PET (5 mice/group) on D+6, D+9, D+13, and D+16 (days after treatment). At each time point, 4 mice per group were sacrificed for quantification of the different tumor cell fractions by flow cytometry and histopathology. Changes in (18)F-FDG uptake were correlated with inflammation and viable tumor cells.


RESULTS
Cyclophosphamide administration resulted in a steady reduction in viable cell fraction until D+9 (reduction from baseline, -64%). The viable cell fraction increased again on D+13. A transient influx of inflammatory cells was seen from D+6 to D+13 (peak on D+9, 24% of total cell fraction). After hydrocortisone administration, a similar reduction in the viable cell fraction was seen. The inflammatory response was less pronounced but developed with earlier kinetics (peak on D+6 [15% of total cell fraction], almost resolved on D+9) and consisted primarily of granulocytes instead of mononuclear cells in the absence of corticosteroids. In both groups, a significant reduction in (18)F-FDG uptake was seen until D+6. On D+9, a transient increase in (18)F-FDG uptake was seen in group A, whereas a further decrease was observed in group B.


CONCLUSIONS
After corticosteroid administration, the contribution of inflammatory cells to the (18)F-FDG uptake was less important than that in mice treated with chemotherapy alone. The earlier, but weaker, inflammatory response after corticosteroid administration consists primarily of granulocytes instead of mononuclear cells.
Brepoels
Lieselot
L
Department of Nuclear Medicine, University Hospital Gasthuisberg and Catholic University Leuven, Leuven, Belgium.
Stroobants
Sigrid
S
Vandenberghe
Peter
P
Spaepen
Karoline
K
Dupont
Patrick
P
Nuyts
Johan
J
Bormans
Guy
G
Mortelmans
Luc
L
Verhoef
Gregor
G
De Wolf-Peeters
Christiane
C
D000818:Animals; D003520:Cyclophosphamide / Q000627:therapeutic use; D005260:Female; D005434:Flow Cytometry; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D049268:Positron-Emission Tomography
D019788:Fluorodeoxyglucose F18; D003520:Cyclophosphamide; D006854:Hydrocortisone