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Am J Nucl Med Mol Imaging 2012;2(1):110-121.
Original Article
Molecular imaging of therapy response with 18F-FLT-PET following
cyclophosphamide and mTOR inhibition
Marijke De Saint-Hubert, Lieselot Brepoels, Ellen Devos, Peter Vermaelen, Tjibe De Groot, Thomas Tousseyn, Luc Mortelmans, Felix
M Mottaghy
Department of Nuclear Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands; Department of Nuclear
Medicine, Katholieke Universiteit Leuven, Leuven, Belgium; Laboratory for Radiopharmacy, Katholieke Universiteit Leuven, Leuven,
Belgium; Morphology and Molecular Pathology, Katholieke Universiteit Leuven, Leuven, Belgium; Department of Nuclear Medicine,
University Hospital RWTH Aachen, Germany.
Received November 5, 2011; accepted November 18, 2011; Epub December 15, 2011; Published January 1, 2012
Abstract: Purpose: Evaluation and comparison of FLT-PET and FDG-PET to monitor early response following both
cyclophosphamide and temsirolimus treatment in a mouse model of Burkitt lymphoma. Procedures: Daudi xenograft mice were
treated with either cyclophosphamide or temsirolimus and imaged with FLT-PET and FDG-PET on appropriate days post therapy
inititiation. Immunohistochemical (IHC) studies (H&E, TUNEL, CD20, PCNA and ki-67) and DNA flow cytometry studies were
performed. Results: FDG tumor uptake decreased immediately after cyclophosphamide treatment while FLT-PET showed only a late
and less pronounced decrease. A fast induction of apoptosis was observed together with an early accumulation of cells in the S-
phase, suggesting DNA repair. Temsirolimus treatment reduced both FDG and FLT tumor uptake immediately after therapy and
resulted in a fast induction of apoptosis and G0-G1 phase accumulation. Conclusion: FLT response was less distinct than FDG
response and may be controlled by DNA repair early after cyclophosphamide. Nevertheless, FLT-PET was able to reflect decreased
proliferation following temsirolimus. (ajnmmi1111001).
Keywords: FDG-PET – FLT-PET – Therapy response imaging
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Address all correspondence to:
Dr. Marijke De Saint-Hubert
Nuclear Medicine, Maastricht University Medical Center
P.O. Box 5800, 6202 AZ Maastricht
The Netherlands, Tel.: +31-43-3874738, Fax: +31-43-3876746
E-mail: Marijke.De.SaintHubert@mumc.nl