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

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.

BioXmark® liquid fiducials to enable radiotherapy tumor boosting in rectal cancer, a feasibility trial

“…did the same in pancreatic tumors [29] . In vivo measurements of the stability of the marker over a 5-month period showed movement of less than 2 mm [30] . Hence, fiducial markers may provide a potential benefit in gastrointestinal tumors to allow for precise day-to-day position verification.…”

A scoping review of small animal image-guided radiotherapy research: Advances, impact and future opportunities in translational radiobiology

“…Some developments have been made with the implementation of iodinated and nanoparticle-based contrast agents which have dual benefits of enhancement of CT image contrast and therapeutic dose deposition [4] , [28] . Some studies (2%) have also shown the possibility of improved targeting accuracy of low contrast tissues using fiducial markers for treatment alignment [29] .…”

A liquid immunogenic fiducial eluter for image-guided radiotherapy

“…Liquid fiducial markers have the additional advantage of minimizing migration over time ( 6 , 7 ) and minimizing any image artifacts ( 8 , 9 ). Previous studies have further indicated that liquid fiducials are safer and easier to inject at the targeted site compared to solid fiducials that may require endoscopic implantation, which may be more complex for resource-limited settings and may be uncomfortable procedure for the patient ( 10 , 11 ). Recent studies have highlighted the use of liquid fiducials to improve image-guided radiotherapy in different types of tumors e.g.…”