Abstract
Clinical use of DC Bead™ loaded with doxorubicin (DEBDOX™) or irinotecan (DEBIRI™), for the treatment of primary and secondary tumours of the liver respectively, is showing great promise. Recently there has been a tendency to select smaller bead size ranges to treat tumours in an effort to allow more drug dose to be administered, improve tumoural penetration and resultant drug delivery and tumour coverage. Herein we describe the development and performance characterisation of a new DC Bead size range (DC BeadM1TM, 70–150 μm) capable of an increased bead delivery in the distal vasculature, corresponding to greater tumour coverage and drug dose delivered. Both unloaded and drug loaded DC BeadM1 were shown to have a greater density of distal volume of penetration although the ultimate distal level of penetration was the same as that of the 100–300 µm beads in an in vitro penetration model. Elution of doxorubicin was slower than irinotecan elution, but it was similar when comparing the same drug elution from 70 to 150 µm compared to 100–300 µm beads. Radiopaque versions of 70–150 and 100–300 µm beads were prepared in order to evaluate distribution ex vivo using µ-CT and doxorubicin distribution using epifluorescent microscopy. Liver distribution of the radiopaque versions of the beads was shown to be more distal and efficient at filling smaller vessels with the DC BeadM1 and correspondingly more beads were found per vessel histologically with a larger area of drug coverage with the smaller size range. This study indicates that the smaller (70–150 μm) beads should permit an increased dose of drug to be administered to both hypervascular and hypovascular tumours as compared to 100–300 µm beads.
Highlights
Transarterial chemoembolisation (TACE) has been practiced in patients for over 3 decades [1, 2] and describes the targeted delivery of chemotherapeutic agents followed by embolic material(s) to hypervascular liver tumors through a catheter placed in the tumor supplying arteries [3]
The tighter size distribution of 70–150 lm limits the likelihood of in vivo premature occlusion. This is demonstrated in this study (Fig. 6) in which we have investigated the distribution in a tumour-bearing rabbit liver, where we see that the 100–300 lm beads have a tendency to occlude and accumulate in the larger, proximal and more central hepatic arteries, whereas the 70–150 lm beads are seen clearly occupying the smaller, more distal and peripheral arteries and those surrounding the tumour (Fig. 7)
As clinical experience is mounting for the use of drug eluting beads (DEB) for the treatment of hepatic malignancies, techniques for bead administration (e.g. ‘‘embo-light’’ versus stasis [5] ) have advanced along with refinement of drug dose and bead size selection
Summary
Transarterial chemoembolisation (TACE) has been practiced in patients for over 3 decades [1, 2] and describes the targeted delivery of chemotherapeutic agents followed by embolic material(s) to hypervascular liver tumors through a catheter placed in the tumor supplying arteries [3]. There is no worldwide standard technique [4], conventional TACE (cTACE) is most often performed by emulsifying chemotherapeutics with LipiodolÒ and infusing this emulsion through the catheter prior to delivery of the embolic material. Drug-eluting bead TACE (DEB-TACE) has emerged as an alternative to cTACE [5]. Use of DEB-TACE has recently increased, clinical practice is still evolving with regard to technique and material choice. The most commonly used [4] and well characterised DEB is DC Bead, which is a microspherical embolisation device composed of acrylamido polyvinyl alcohol–co– acrylamido-2-methylpropane sulfonate capable of loading and eluting positively-charged drugs such as doxorubicin or irinotecan via an ion exchange process [6,7,8,9,10,11].
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