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.