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Am J Nucl Med Mol Imaging 2014;4(1):70-79
Original Article
Molecular imaging for early prediction of response to Sorafenib treatment in
sarcoma
Zhoulei Li, Ken Herrmann, Sabine Pirsig, Kathrin Philipp-Abbrederis, Martin Henninger, Michaela Aichler, Annette Feuchtinger, Axel
Walch, Ambros J Beer, Ingo Ringshausen, Kelsey L Pomykala, Klemens Scheidhauer, Markus Schwaiger, Ulrich Keller, Andreas K
Buck
Department of Nuclear Medicine, Technische Universität München, Ismaninger Strasse 22, D-81675 Munich, Germany; Department
of Nuclear Medicine, Universität Würzburg, Oberdürrbacher Strasse 6, D-97080 Würzburg, Germany; Department of Internal Medicine
III, Technische Universität München, Ismaninger Strasse 22, D-81675 Munich, Germany; Insititute of Pathology, Helmholtz Zentrum
München and Technische Universität München, Ismaninger Strasse 22, D-81675 Munich, Germany; Division of Ahmanson
Translational Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at University California
Los Angeles, 10833 Le Conte Avenue, Room AR-249 CHS, Los Angeles, CA 90095-1782, USA
Received September 22, 2013; Accepted November 19, 2013; Epub December 15, 2013; Published January 1, 2014
Abstract: The role of [18F]fluorodeoxyglucose ([18F]FDG) PET in staging of sarcoma is well established. The aim of this preclinical
study was to compare [18F]fluorothymidine ([18F]FLT) PET to [18F]FDG PET regarding early metabolic changes of sarcoma in the
course of targeted cancer therapy. SCID mice bearing sarcoma A673 xenotransplants were used for investigation of tumor response
after treatment with the multikinase inhibitor Sorafenib. [18F]FLT and/or [18F]FDG-PET were performed prior to and early after
initiation of treatment. Tumoral uptake (% Injected Dose per gram (%ID/g) of [18F]FLT-PET was compared to [18F]FDG-PET. Results
were correlated with histopathology and in vitro data including cellular uptake, cell cycle-related protein expression, cell cycle
distribution and apoptosis. In vitro experiments showed that A673 cells were sensitive to Sorafenib. In vivo, tumor growth was
inhibited in comparison to a 4-fold increase of the tumor volume in control mice. Using [18F]FDG as tracer, a moderate reduction in
tracer uptake (n=15, mean relative %ID/g 74%, range 35%-121%, p=0.03) was observed. The decrease in %ID/g using [18F]FLT-PET
was significantly higher (p=0.003). The mean relative %ID/g in [18F]FLT uptake on day + 5 was significantly reduced to 54%
compared to baseline (n=15, range 24%-125%, SD=29%). The PET analysis 24 hr after therapy showed a significant reduction of the
mean [18F]FLT-%ID/g (p=0.04). The reduction of %ID/g on day + 1 in [18F]FDG-PET was not statistically significant (p=0.99). In
conclusion, both [18F]FDG- and [18F]FLT-PET were able to predict response to Sorafenib treatment. In contrast to [18F]FDG-PET,
[18F]FLT-PET was more predictive for very early response to treatment. (ajnmmi1309005).
Keywords: Molecular imaging, sarcoma, PET, proliferation, [18F]FLT, [18F]FDG
Address correspondence to: Dr. Andreas K Buck, Department of Nuclear Medicine, Universitätsk-linikum Würzburg, Oberdürrbacher
Strasse 6, D-97080 Würzburg, Germany. Tel: +49-931 201-35001; Fax: +49-931 201-635000; E-mail: buck_a@ukw.de
Original Article
Molecular imaging for early prediction of response to Sorafenib treatment in
sarcoma
Zhoulei Li, Ken Herrmann, Sabine Pirsig, Kathrin Philipp-Abbrederis, Martin Henninger, Michaela Aichler, Annette Feuchtinger, Axel
Walch, Ambros J Beer, Ingo Ringshausen, Kelsey L Pomykala, Klemens Scheidhauer, Markus Schwaiger, Ulrich Keller, Andreas K
Buck
Department of Nuclear Medicine, Technische Universität München, Ismaninger Strasse 22, D-81675 Munich, Germany; Department
of Nuclear Medicine, Universität Würzburg, Oberdürrbacher Strasse 6, D-97080 Würzburg, Germany; Department of Internal Medicine
III, Technische Universität München, Ismaninger Strasse 22, D-81675 Munich, Germany; Insititute of Pathology, Helmholtz Zentrum
München and Technische Universität München, Ismaninger Strasse 22, D-81675 Munich, Germany; Division of Ahmanson
Translational Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at University California
Los Angeles, 10833 Le Conte Avenue, Room AR-249 CHS, Los Angeles, CA 90095-1782, USA
Received September 22, 2013; Accepted November 19, 2013; Epub December 15, 2013; Published January 1, 2014
Abstract: The role of [18F]fluorodeoxyglucose ([18F]FDG) PET in staging of sarcoma is well established. The aim of this preclinical
study was to compare [18F]fluorothymidine ([18F]FLT) PET to [18F]FDG PET regarding early metabolic changes of sarcoma in the
course of targeted cancer therapy. SCID mice bearing sarcoma A673 xenotransplants were used for investigation of tumor response
after treatment with the multikinase inhibitor Sorafenib. [18F]FLT and/or [18F]FDG-PET were performed prior to and early after
initiation of treatment. Tumoral uptake (% Injected Dose per gram (%ID/g) of [18F]FLT-PET was compared to [18F]FDG-PET. Results
were correlated with histopathology and in vitro data including cellular uptake, cell cycle-related protein expression, cell cycle
distribution and apoptosis. In vitro experiments showed that A673 cells were sensitive to Sorafenib. In vivo, tumor growth was
inhibited in comparison to a 4-fold increase of the tumor volume in control mice. Using [18F]FDG as tracer, a moderate reduction in
tracer uptake (n=15, mean relative %ID/g 74%, range 35%-121%, p=0.03) was observed. The decrease in %ID/g using [18F]FLT-PET
was significantly higher (p=0.003). The mean relative %ID/g in [18F]FLT uptake on day + 5 was significantly reduced to 54%
compared to baseline (n=15, range 24%-125%, SD=29%). The PET analysis 24 hr after therapy showed a significant reduction of the
mean [18F]FLT-%ID/g (p=0.04). The reduction of %ID/g on day + 1 in [18F]FDG-PET was not statistically significant (p=0.99). In
conclusion, both [18F]FDG- and [18F]FLT-PET were able to predict response to Sorafenib treatment. In contrast to [18F]FDG-PET,
[18F]FLT-PET was more predictive for very early response to treatment. (ajnmmi1309005).
Keywords: Molecular imaging, sarcoma, PET, proliferation, [18F]FLT, [18F]FDG
Address correspondence to: Dr. Andreas K Buck, Department of Nuclear Medicine, Universitätsk-linikum Würzburg, Oberdürrbacher
Strasse 6, D-97080 Würzburg, Germany. Tel: +49-931 201-35001; Fax: +49-931 201-635000; E-mail: buck_a@ukw.de
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