Chemical stability of BioXmark® following normofractionated and single-fraction proton beam therapy

Purpose/Objective
Use of solid fiducial markers in proton radiation therapy has been approached with care as their presence may cause significant local dose perturbations. Recently, a liquid carbohydrate based fiducial marker (BioXmark®) has been introduced with minimal dose perturbation (relative stopping power = 1.164) and visibility properties suitable for use in image-guided proton therapy (IGPT). The purpose of this work was to investigate the chemical stability of the marker for use in both normofractionated and single fraction proton treatment regimes.

Material/Methods
Ten identical custom-made cylindrical polymethylmethacrylate (PMMA) inserts (V = 0.95 mL, douter = 10.0 mm, dinner = 5.0 mm, l = 48 mm) were prepared. BioXmark® markers (150±30 mg) were added to the bottom of the inserts and water (700 μL) was added on top of the markers. The inserts were sealed with a rubber stopper.
A QA dosimetry phantom was modified to accommodate four PMMA inserts simultaneously by inserting these sideway into the proton irradiation field (10 × 10cm) (Figure 1). Four markers (Group A) were irradiated during daily QA for a period of 51 days with 43 fractions ranging from 1.44-1.86 Gy resulting in an accumulated dose of 67.4 Gy. Four other markers (Group B) were irradiated with a single dose of 155.4 Gy and two non-irradiated Control markers were kept on site for the duration of the experiments.
Possible chemical alterations caused by proton irradiation were evaluated by high-performance liquid chromatography (HPLC), electrospray ionization mass spectrometry (ESI-MS),thin-layer chromatography (TLC) and visual inspection of the markers and the aqueous phase above the markers.

Results
No visual alterations between markers from Group A+B and the Control markers were observed. HPLC and TLC analysis of the markers and the aqueous phase above the markers from all three groups did not indicate chemical degradation of the marker materials (Figure 2). This observation was further supported by ESI-MS analysis, which showed identical m/z fragments for all three groups (Figure 2).

Conclusion
The BioXmark®marker showed no chemical degradation after exposure to normofractionated and extremely hypofractionated proton therapy regimes and may serve as a good alternative to solid fiducial markers used for IGPT.