Lydia Koi1, Ralf Bergmann2, Kerstin Brüchner3, Jens Pietzsch4, Hans-Jürgen Pietzsch4, Mechthild Krause5, Jörg Steinbach4, Daniel Zips6, Michael Baumann7. 1. Department of Radiation Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; OncoRay-National Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Germany. 2. Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden - Rossendorf, Germany. 3. Department of Radiation Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; OncoRay-National Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Germany; Institute of Radiation Oncology, Helmholtz-Zentrum Dresden - Rossendorf, Germany. 4. Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden - Rossendorf, Germany; Department of Chemistry and Food Chemistry, Technische Universität Dresden, Germany. 5. Department of Radiation Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; OncoRay-National Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Germany; Institute of Radiation Oncology, Helmholtz-Zentrum Dresden - Rossendorf, Germany; German Cancer Consortium (DKTK), Partner Site Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany. 6. Department of Radiation Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; OncoRay-National Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Germany; Department of Radiation Oncology, University Hospital, Eberhard Karls Universität Tübingen, Germany. 7. Department of Radiation Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; OncoRay-National Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Germany; Institute of Radiation Oncology, Helmholtz-Zentrum Dresden - Rossendorf, Germany; German Cancer Consortium (DKTK), Partner Site Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address: michael.baumann@uniklinikum-dresden.de.
Abstract
PURPOSE: The effect of radioimmunotherapy (RIT) using the therapeutic radionuclide Y-90 bound to the anti-EGFR antibody cetuximab combined with external beam irradiation (EBRT) (EBRIT) on permanent local tumor control in vivo was examined. METHODS: Growth delay was evaluated in three human squamous cell carcinoma models after RIT with [(90)Y]Y-(CHX-A''-DTPA)₄-cetuximab (Y-90-cetuximab). The EBRT dose required to cure 50% of the tumors (TCD₅₀) for EBRT alone or EBRIT was evaluated in one RIT-responder (FaDu) and one RIT-non-responder (UT-SCC-5). EGFR expression and microenvironmental parameters were evaluated in untreated tumors, bioavailability was visualized by PET using ([(86)Y]Y-(CHX-A''-DTPA)₄-cetuximab (Y-86-cetuximab) and biodistribution using Y-90-cetuximab. RESULTS: In UT-SCC-8 and FaDu but not in UT-SCC-5 radiolabeled cetuximab led to significant tumor growth delay. TCD₅₀ after EBRT was significantly decreased by EGFR-targeted RIT in FaDu but not in UT-SCC-5. In contrast to EGFR expression, parameters of the tumor micromilieu and in particular the Y-90-cetuximab biodistribution or Y-86-cetuximab visualization in PET correlated with the responsiveness to RIT or EBRIT. CONCLUSION: EGFR-targeted EBRIT can improve permanent local tumor control compared to EBRT alone. PET imaging of bioavailability of labeled cetuximab appears to be a suitable predictor for response to EBRIT. This theragnostic approach should be further explored for clinical translation.
PURPOSE: The effect of radioimmunotherapy (RIT) using the therapeutic radionuclide Y-90 bound to the anti-EGFR antibody cetuximab combined with external beam irradiation (EBRT) (EBRIT) on permanent local tumor control in vivo was examined. METHODS: Growth delay was evaluated in three humansquamous cell carcinoma models after RIT with [(90)Y]Y-(CHX-A''-DTPA)₄-cetuximab (Y-90-cetuximab). The EBRT dose required to cure 50% of the tumors (TCD₅₀) for EBRT alone or EBRIT was evaluated in one RIT-responder (FaDu) and one RIT-non-responder (UT-SCC-5). EGFR expression and microenvironmental parameters were evaluated in untreated tumors, bioavailability was visualized by PET using ([(86)Y]Y-(CHX-A''-DTPA)₄-cetuximab (Y-86-cetuximab) and biodistribution using Y-90-cetuximab. RESULTS: In UT-SCC-8 and FaDu but not in UT-SCC-5 radiolabeled cetuximab led to significant tumor growth delay. TCD₅₀ after EBRT was significantly decreased by EGFR-targeted RIT in FaDu but not in UT-SCC-5. In contrast to EGFR expression, parameters of the tumor micromilieu and in particular the Y-90-cetuximab biodistribution or Y-86-cetuximab visualization in PET correlated with the responsiveness to RIT or EBRIT. CONCLUSION:EGFR-targeted EBRIT can improve permanent local tumor control compared to EBRT alone. PET imaging of bioavailability of labeled cetuximab appears to be a suitable predictor for response to EBRIT. This theragnostic approach should be further explored for clinical translation.
Authors: Eduardo Aluicio-Sarduy; Paul A Ellison; Todd E Barnhart; Weibo Cai; Robert Jerry Nickles; Jonathan W Engle Journal: J Labelled Comp Radiopharm Date: 2018-03-12 Impact factor: 1.921
Authors: Ina Kurth; Linda Hein; Katrin Mäbert; Claudia Peitzsch; Lydia Koi; Monica Cojoc; Leoni Kunz-Schughart; Michael Baumann; Anna Dubrovska Journal: Oncotarget Date: 2015-10-27
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