BioXmark for high-precision radiotherapy in an orthotopic pancreatic tumor mouse model

Experiences with a liquid fiducial marker
  • S. Dobiasch
  • S. Kampfer
  • R. Burkhardt
  • D. Schilling
  • T. E. Schmid
  • J. J. Wilkens
  • S. E. Combs
Original Article

Abstract

Background and purpose

High-precision radiotherapy (RT) requires precise positioning, particularly with high single doses. Fiducial markers in combination with onboard imaging are excellent tools to support this. The purpose of this study is to establish a pancreatic cancer mouse model for high-precision image-guided RT (IGRT) using the liquid fiducial marker BioXmark (Nanovi, Kongens Lyngby, Denmark).

Methods

In an animal-based cancer model, different volumes of BioXmark (10–50 µl), application forms, and imaging modalities—cone-beam computer tomography (CBCT) incorporated in either the Small Animal Radiation Research Platform (SARRP) or the small-animal micro-CT Scanner (SkyScan; Bruker, Brussels, Belgium)—as well as subsequent RT with the SARRP system were analyzed to derive recommendations for BioXmark.

Results

Even small volumes (10 µl) of BioXmark could be detected by CBCT (SARRP and Skyscan). Larger volumes (50 µl) led to hardening artefacts. The position of BioXmark was monitored at least weekly by CBCT and was stable over 4 months. BioXmark was shown to be well tolerated; no changes in physical condition or toxic side effects were observed in comparison to control mice. BioXmark enabled an exact fusion with the original treatment plan with less hardening artefacts, and minimized the application of contrast agent for fractionated RT.

Conclusion

An orthotopic pancreatic tumor mouse model was established for high-precision IGRT using a fiducial marker. BioXmark was successfully tested and provides the perfect basis for improved imaging in high-precision RT. BioXmark enables a unique application method and optimal targeted precision in fractionated RT. Therefore, preclinical trials evaluating novel fractionation regimens and/or combination treatment with high-end RT can be performed.

Keywords

Models, animal Cone-beam computed tomography Pancreatic neoplasms Dose fractionation Radiotherapy, image-guided 

BioXmark für die Hochpräzisionsstrahlentherapie im orthotopen Pankreastumor-Mausmodell

Erfahrungen mit einem liquiden Marker

Zusammenfassung

Hintergrund und Zielsetzung

Die Hochpräzisionsstrahlentherapie (RT) erfordert insbesondere bei hohen Einzeldosen eine exakte Lagerung. Marker in Kombination mit integrierten Bildgebungsverfahren können dies optimal gewährleisten. Ziel dieser Arbeit ist die Etablierung eines präklinischen Tumormausmodells zur bildgestützten Strahlentherapie (IGRT) des Pankreaskarzinoms unter Verwendung des liquiden Markers BioXmark (Nanovi, Kongens Lyngby, Dänemark).

Methoden

In einem tierbasierten Tumormodell wurden verschiedene Volumina von BioXmark (10–50 µl), Injektionsformen, Bildgebungsmodalitäten – Kegelstrahl-Computertomographie (CBCT) integriert in SARRP (Small Animal Radiation Research Platform) und Kleintier-Mikro-CT (SkyScan, Bruker, Brüssel, Belgien) – sowie die anschließende RT mittels SARRP analysiert, um daraus Empfehlungen für BioXmark abzuleiten.

Ergebnisse

Selbst kleine Volumina (10 µl) von BioXmark ließen sich im CBCT (SARRP und Skyscan) detektieren. Größere Volumina (50 µl) führten zu milden Artfakten. Die BioXmark-Position wurde wöchentlich mittels CBCT geprüft und war für 4 Monate stabil. BioXmark war sehr gut verträglich; es traten keine physischen Veränderungen oder Nebenwirkungen im Vergleich zu unbehandelten Kontrollmäusen auf. BioXmark ermöglicht artefaktarm die zielgenaue Fusion mit dem ursprünglichen Bestrahlungsplan und minimiert die Verabreichung von Kontrastmittel bei fraktionierter RT.

Schlussfolgerung

Erstmalig wurde ein orthotopes Pankreastumor-Mausmodell für eine Hochpräzisions-IGRT mit liquiden Markern etabliert. BioXmark wurde erfolgreich in einem präklinischen Tiermodell getestet und bietet die ideale Basis zur verbesserten Bildgebung bei der Hochpräzisions-RT. BioXmark erlaubt eine einzigartige Applikationsweise und optimale Zielrichtung bei der fraktionierten RT. Dadurch können präklinische Experimente zur Evaluation neuer Fraktionierungsschemata und/oder Kombinationsbehandlungen mit High-End-RT durchgeführt werden.

Schlüsselwörter

Tiermodelle Cone-Beam-Computertomographie Pankreasneoplasien Dosisfraktionierung Bildgestützte Strahlentherapie 

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Copyright information

© Springer-Verlag GmbH Deutschland 2017

Authors and Affiliations

  • S. Dobiasch
    • 1
    • 4
  • S. Kampfer
    • 1
    • 3
  • R. Burkhardt
    • 1
    • 2
    • 3
  • D. Schilling
    • 1
    • 2
  • T. E. Schmid
    • 1
    • 2
  • J. J. Wilkens
    • 1
    • 2
    • 3
  • S. E. Combs
    • 1
    • 2
    • 4
  1. 1.Department of Radiation OncologyTechnical University of Munich (TUM), Klinikum rechts der IsarMunichGermany
  2. 2.Institute of Innovative Radiotherapy (iRT), Department of Radiation Sciences (DRS)Helmholtz Zentrum MünchenNeuherbergGermany
  3. 3.Physics Department, Technical University of Munich (TUM)GarchingGermany
  4. 4.Partner Site MunichDeutsches Konsortium für Translationale Krebsforschung (DKTK)MunichGermany

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