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

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.