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

Molecular imaging for early prediction of response to Sorafenib treatment in sarcoma

Am J Nucl Med Mol Imaging. 2013 Dec 15;4(1):70-9. eCollection 2013.

Authors

Affiliations

¹ Department of Nuclear Medicine, Technische Universität München Ismaninger Strasse 22, D-81675 Munich, Germany.
² 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 ; 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.
³ Department of Internal Medicine III, Technische Universität München Ismaninger Strasse 22, D-81675 Munich, Germany.
⁴ Insititute of Pathology, Helmholtz Zentrum München and Technische Universität München Ismaninger Strasse 22, D-81675 Munich, Germany.
⁵ 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.
⁶ 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.

PMID: 24380047
PMCID: PMC3867731

Abstract

The role of [(18)F]fluorodeoxyglucose ([(18)F]FDG) PET in staging of sarcoma is well established. The aim of this preclinical study was to compare [(18)F]fluorothymidine ([(18)F]FLT) PET to [(18)F]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. [(18)F]FLT and/or [(18)F]FDG-PET were performed prior to and early after initiation of treatment. Tumoral uptake (% Injected Dose per gram (%ID/g) of [(18)F]FLT-PET was compared to [(18)F]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 [(18)F]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 [(18)F]FLT-PET was significantly higher (p=0.003). The mean relative %ID/g in [(18)F]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 [(18)F]FLT-%ID/g (p=0.04). The reduction of %ID/g on day + 1 in [(18)F]FDG-PET was not statistically significant (p=0.99). In conclusion, both [(18)F]FDG- and [(18)F]FLT-PET were able to predict response to Sorafenib treatment. In contrast to [(18)F]FDG-PET, [(18)F]FLT-PET was more predictive for very early response to treatment.

Keywords: Molecular imaging; PET; [18F]FDG; [18F]FLT; proliferation; sarcoma.