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Comparison of [18F]-Tracers in Various Experimental Tumor Models by PET Imaging and Identification of an Early Response Biomarker for the Novel Microtubule Stabilizer Patupilone

Ebenhan, T. ; Honer, M. ; Ametamey, S.M. ; Schubiger, P.A. ; Becquet, M. ; Ferretti, S. ; Cannet, C. ; Rausch, M. ; McSheehy, P.M.J.

In: Molecular Imaging and Biology, 2009, vol. 11, no. 5, p. 308-321

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    Title
    • Comparison of [18F]-Tracers in Various Experimental Tumor Models by PET Imaging and Identification of an Early Response Biomarker for the Novel Microtubule Stabilizer Patupilone
    Author
    • Ebenhan, T.. Global Imaging Group, Novartis Institute of Biomedical Research, 4002, Basel, Switzerland
    • Honer, M.. Animal Imaging Center-PET, Center for Radiopharmaceutical Science, Eidgenoessische Technische Hochschule (ETH) Zurich, Wolfgang-Pauli-Strasse 10, CH-8093, Zurich, Switzerland
    • Ametamey, S.M.. Animal Imaging Center-PET, Center for Radiopharmaceutical Science, Eidgenoessische Technische Hochschule (ETH) Zurich, Wolfgang-Pauli-Strasse 10, CH-8093, Zurich, Switzerland
    • Schubiger, P.A.. Animal Imaging Center-PET, Center for Radiopharmaceutical Science, Eidgenoessische Technische Hochschule (ETH) Zurich, Wolfgang-Pauli-Strasse 10, CH-8093, Zurich, Switzerland
    • Becquet, M.. Oncology Research, Novartis Institute of Biomedical Research, 4002, Basel, Switzerland
    • Ferretti, S.. Oncology Research, Novartis Institute of Biomedical Research, 4002, Basel, Switzerland
    • Cannet, C.. Global Imaging Group, Novartis Institute of Biomedical Research, 4002, Basel, Switzerland
    • Rausch, M.. Global Imaging Group, Novartis Institute of Biomedical Research, 4002, Basel, Switzerland
    • McSheehy, P.M.J.. Oncology Research, Novartis Institute of Biomedical Research, 4002, Basel, Switzerland
    Document Type
    • Postprint
    OAI-PMH Identifier
    • oai:doc.rero.ch:314174
    Summary
    Purpose: The suitability of [18F]FDG, [18F]FLT, [18F]FET, and [18F]FCH as non-invasive positron emission tomography (PET) biomarkers for monitoring response to chemotherapy was analyzed in various experimental tumor models. Procedures: Tracer uptake into three syngeneic rodent tumor models and ten human xenograft models was evaluated using semiquantitative analysis of small-animal PET data. Murine RIF-1 fibrosarcomas and [18F]FLT were selected to monitor the effects of the novel cytotoxic patupilone. Results: Except [18F]FCH, all tracers provided good tumor visualization. Highest [18F]FDG uptake was identified in syngeneic tumors. Xenograft models, however, showed low [18F]FDG SUVs and were better visualized by [18F]FLT. Monitoring the effects of patupilone on [18F]FLT uptake in RIF-1 tumors revealed a significant decrease of tracer uptake after 24h, which strongly negatively correlated with apoptosis. Conclusion: [18F]FLT PET of experimental tumors is a viable complement to [18F]FDG for preclinical drug development. [18F]FLT may be an excellent biomarker for patupilone-induced apoptosis