In situ evaluation of spatiotemporal distribution of doxorubicin from Drug-eluting Beads in a tissue mimicking phantom

Understanding the intra-tumoral distribution of chemotherapeutic drugs is extremely important in predicting therapeutic outcome. Tissue mimicking gel phantoms are useful for studying drug distribution in vitro but quantifying distribution is laborious due to the need to section phantoms over the relevant time course and individually quantify drug elution. In this study we compare a bespoke version of the traditional phantom sectioning approach, with a novel confocal microscopy technique that enables dynamic in situ measurements of drug concentration. Release of doxorubicin from Drug-eluting Embolization Beads (DEBs) was measured in phantoms composed of alginate and agarose over comparable time intervals. Drug release from several different types of bead were measured. The non-radiopaque DC BeadTM generated a higher concentration at the boundary between the beads and the phantom and larger drug penetration distance within the release period, compared with the radiopaque DC Bead LUMITM. This is likely due to the difference of compositional and structural characteristics of the hydrogel beads interacting differently with the loaded drug. Comparison of in vitro results against historical in vivo data show good agreement in terms of drug penetration, when confounding factors such as geometry, elimination and bead chemistry were accounted for. Hence these methods have demonstrated potential for both bead and gel phantom validation, and provide opportunities for optimisation of bead design and embolization protocols through in vitro-in vivo comparison.

Automated summary

The study compared a custom version of the traditional phantom sectioning approach with a novel confocal microscopy technique for drug distribution measurements, finding that confocal microscopy enables real-time measurement of drug concentration. Different types of beads exhibited variations in drug concentration and penetration distance. Comparison of in vitro results with historical in vivo data showed good consistency.