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Journal of Nuclear Medicine Vol. 48 No. 3 390-397
© 2007 by Society of Nuclear Medicine


Basic Science Investigation

Effect of Corticosteroids on 18F-FDG Uptake in Tumor Lesions After Chemotherapy

Lieselot Brepoels1,2, Sigrid Stroobants1,2, Peter Vandenberghe3, Karoline Spaepen1, Patrick Dupont1,2, Johan Nuyts1,2, Guy Bormans2,4, Luc Mortelmans1,2, Gregor Verhoef5 and Christiane De Wolf-Peeters6

1 Department of Nuclear Medicine, University Hospital Gasthuisberg and Catholic University Leuven, Leuven, Belgium; 2 Molecular Small Animal Imaging Center, University Hospital Gasthuisberg and Catholic University Leuven, Leuven, Belgium; 3 Center of Human Genetics, University Hospital Gasthuisberg and Catholic University Leuven, Leuven, Belgium; 4 Laboratory for Radiopharmacy, University Hospital Gasthuisberg and Catholic University Leuven, Leuven, Belgium; 5 Department of Hematology, University Hospital Gasthuisberg and Catholic University Leuven, Leuven, Belgium; and 6 Department of Pathology, University Hospital Gasthuisberg and Catholic University Leuven, Leuven, Belgium

Correspondence: For correspondence contact: Lieselot Brepoels, MD, Department of Nuclear Medicine, University Hospital Gasthuisberg, Leuven Herestraat 49, 3000 Leuven, Belgium. E-mail: lieselot.brepoels{at}uz.kuleuven.be

To be a reliable predictor of response, 18F-FDG uptake should reflect changes in the amount of viable tumor cells. However, 18F-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 18F-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 18F-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 18F-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 18F-FDG uptake was seen until D+6. On D+9, a transient increase in 18F-FDG uptake was seen in group A, whereas a further decrease was observed in group B. Conclusion: After corticosteroid administration, the contribution of inflammatory cells to the 18F-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.

Key Words: therapy response • 18F-FDG • corticosteroids • mice • small-animal PET

COPYRIGHT © 2007 by the Society of Nuclear Medicine, Inc.


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L. Brepoels, S. Stroobants, G. Verhoef, T. De Groot, L. Mortelmans, and C. De Wolf-Peeters
18F-FDG and 18F-FLT Uptake Early After Cyclophosphamide and mTOR Inhibition in an Experimental Lymphoma Model
J. Nucl. Med., July 1, 2009; 50(7): 1102 - 1109.
[Abstract] [Full Text] [PDF]




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