Radiotherapy enhances uptake and efficacy of 90Y-cetuximab: A preclinical trial.

Abstract

BACKGROUND AND PURPOSE:

Systemic molecular radiotherapy utilizes internal irradiation by radionuclide-labeled tumor-targeting agents with the potential to destroy (micro-)metastases. However, doses that are applicable in solid tumors do not reach the levels nessecary for tumor control. Thus, the combination of molecular and external radiotherapy is a promising treatment strategy, as enhanced tumor doses can be delivered with and without minor overlapping toxicities. Here, we combined a 90Y-labeled anti-EGFR antibody (Cetuximab) with clinically relevant fractionated radiotherapy in a preclinical trial using head and neck squamous cell carcinoma xenograft tumors.

MATERIALS AND METHODS:

To model 90Y-Cetuximab uptake for treatment schedule optimization, FaDu-bearing mice were injected with near-infrared-labeled-Cetuximab at different time points during radiotherapy with differing doses. Cetuximab uptake was longitudinally followed by in vivo-optical imaging. Tumor control probability experiments with fractionated radiotherapy (30 fx, 6 weeks, 8 dose groups/ arm) in combination with 90Y-Cetuximab were performed to test the curative potential.

RESULTS:

Imaging of near-infrared-labeled-Cetuximab uptake revealed that low to moderate external beam doses can enhance antibody uptake. Using the optimized schedule, combination of molecular and external radiotherapy using 90Y-Cetuximab at a dose that did not result in permanent tumor inactivation in previous experiments, led to substantially increased tumor control compared to radiotherapy alone.

CONCLUSION:

Our results indicate that combination of radiolabeled therapeutics with clinically relevant fractionated radiotherapy has a remarkable potential to improve curative treatment outcome. Application of some radiation dose prior to injection may improve drug uptake and enable patient stratification and treatment personalization via a corresponding PET-tracer during therapy.

• Authors: Antje Dietrich, Michael Andreeff, Lydia Koi, Ralf Bergmann, Maik Schubert, Lena Schreiner, Steffen Löck, Wiebke Sihver, Robert Freudenberg, Sandra Hering, Hans-Jürgen Pietzsch, Jörg Steinbach, Jörg Kotzerke, Michael Baumann, Mechthild Krause
• Journal: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology (Radiother Oncol) Vol. 155 Pg. 285-292 (02 2021) ISSN: 1879-0887 [Electronic] Ireland
• PMID: 33227356 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.

Chemical References

• Antibodies, Monoclonal, Humanized
• ErbB Receptors
• Cetuximab

Topics

• Animals
• Antibodies, Monoclonal, Humanized
• Cell Line, Tumor
• Cetuximab
• ErbB Receptors
• Head and Neck Neoplasms
• Humans
• Mice
• Squamous Cell Carcinoma of Head and Neck