Evaluation of a Novel Liquid Fiducial Marker, BioXmark®, for Small Animal Image-Guided Radiotherapy Applications.

Kathryn H Brown,Karl T Butterworth,Mihaela Ghita,Giuseppe Schettino,Kevin M Prise

doi:10.3390/cancers12051276

Kathryn H Brown, Karl T Butterworth + Show 3 more

Open Access

https://doi.org/10.3390/cancers12051276

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Abstract

BioXmark® (Nanovi A/S, Denmark) is a novel fiducial marker based on a liquid, iodine-based and non-metallic formulation. BioXmark® has been clinically validated and reverse translated to preclinical models to improve cone-beam CT (CBCT) target delineation in small animal image-guided radiotherapy (SAIGRT). However, in phantom image analysis and in vivo evaluation of radiobiological response after the injection of BioXmark® are yet to be reported. In phantom measurements were performed to compare CBCT imaging artefacts with solid fiducials and determine optimum imaging parameters for BioXmark®. In vivo stability of BioXmark® was assessed over a 5-month period, and the impact of BioXmark® on in vivo tumour response from single-fraction and fractionated X-ray exposures was investigated in a subcutaneous syngeneic tumour model. BioXmark® was stable, well tolerated and detectable on CBCT at volumes ≤10 µL. Our data showed imaging artefacts reduced by up to 84% and 89% compared to polymer and gold fiducial markers, respectively. BioXmark® was shown to have no significant impact on tumour growth in control animals, but changes were observed in irradiated animals injected with BioXmark® due to alterations in dose calculations induced by the sharp contrast enhancement. BioXmark® is superior to solid fiducials with reduced imaging artefacts on CBCT. With minimal impact on the tumour growth delay, BioXmark® can be implemented in SAIGRT to improve target delineation and reduce set-up errors.

Highlights

Radiotherapy is a major modality in the radical treatment of cancer, being prescribed to >50% of patients during their treatment [1]
Significant advances in radiotherapy technology have enabled increasingly sophisticated, conformal delivery methods to be implemented into routine clinical practice, such as intensity modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT) and stereotactic body radiotherapy (SBRT) [2,3,4]
Imaging artefacts can be defined as discrepancies in cone beam CT (CBCT) scans that are not present in the object under investigation and degrade the quality of the image

Summary

Introduction

Radiotherapy is a major modality in the radical treatment of cancer, being prescribed to >50% of patients during their treatment [1]. Parallel developments in small animal image-guided radiotherapy (SAIGRT) platforms presents the opportunity to closely mimic clinical scenarios and further radiobiological understanding of tumour and normal tissue response [5]. These platforms increase the ability to irradiate small target volumes in vivo with the highest. Several imaging modalities have been used to optimise treatment positioning accuracy and precision, including megavoltage planar imaging, static kilovoltage planar imaging, ultrasound, cone beam CT (CBCT) and portal imaging [6,7,8] These methods have limited soft-tissue contrast, which has driven the recent integration of magnetic resonance imaging (MRI) with linear accelerators (Linac) in the MR-Linac Radiotherapy Systems. The clinical benefits of MRI-guided radiotherapy remain to be fully demonstrated, and it is unlikely this approach will be widely implemented into routine practice for most tumours in the short term

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