Opinion: A review of current embolic agents

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Embolotherapy has become an increasingly popular procedure in the field of interventional radiology. The industry has been very active in developing sophisticated embolic agents including calibrated microspheres for bland embolization, drug-eluting microspheres and radioactive Y-90 microspheres to treat primary or secondary liver disease.

Conventional embolic agents are used mainly to treat intractable haemorrhage and to devascularise benign or malignant tumours. Since they are universally available as opposed to the novel embolization microspheres loaded with medications, this comment will focus on their characteristics. Embolization materials should be first classified according to their physical and biological characteristics.

 

Embolic particles are the most commonly used materials to perform uterine artery, hepatic artery or bronchial artery embolization. Regular non spherical polyvinyl alcohol (PVA) particles have been used for more than 25 years. Calibrated spherical particles made of tris-acryl have been developed to address some of the disadvantages associated with conventional PVA. More recently, three other types of microspheres, based on different polymers have been introduced on the market.


When choosing embolic particles, interventional radiologists should be aware that not all particles are equal. They differ in physical and biological properties including available sizes (or size range), uniformity (i.e. granulometric distribution of the particles compared to the advertised size), aggregation (mainly encountered with regular non spherical PVA particles), compressibility and elastic recovery (potentially leading to a more distal embolization than expected for soft microspheres with a slow elastic recovery) and visibility (coloured microspheres for better suspension and control at the time of injection).


What is the best currently available embolic particle? This frequently asked question remains a matter of debate provoking passionate discussions at scientific meetings and controversies in the literature.


Regular PVA particles do not completely occlude the lumen of the occluded arteries because of their irregular shape and heterogeneous calibration and occlusion is completed by thrombus formation. Non-spherical PVA particles cause moderate perivascular inflammatory change and recanalisation can occur after several months or years. The irregular shape of the material is associated with a larger granulometric range of the particles than advertised. Some of the particles are therefore smaller than expected and may cause distal or non-target embolization of normal tissue. Aggregation of PVA particles can lead to obstruction of the delivery microcatheter and potentially to an uncontrolled level of arterial occlusion. Finally, clumping of the embolic material may result in a false angiographic endpoint at the conclusion of the embolization.


Tris-acryl microspheres are made from precisely calibrated microporous cross-linked acrylic beads embedded with gelatin (Embosphere, Biosphere Medical, Roissy, France). Initially developed for high risk embolization in neuroradiology, tris-acryl microspheres are now considered the most common embolic particle used for uterine fibroid embolization.


­­The following size ranges are currently available: 40–120, 100­–300, 500–700, 700–900 and 900–1200µm. The diameter of occluded arteries correlates well with the microsphere size. The spheres are compressible, which allow easy passage through a microcatheter.


Angiographically, apparent clumping may occur with all types of microspheres and the embolic material redistributes depending on the infusion rate and the concentration. It is recommended to perform the post-embolization angiogram a few minutes (3–5 minutes) after injection of the embolic particle to obtain a true angiographic end point. For uterine fibroid embolization, a targeted embolization can be achieved using a limited uterine artery embolization technique (pruned-tree appearance). In the long-term, there is no chronic inflammatory reaction and no degradation of the polymer.


Two different types of PVA spheres have been recently introduced based on the successful use of tris-acryl microspheres and the long-term trackability of PVA as a polymer (Contour SE, Boston Scientific, Nattick, MA, US and Bead Block, Biocompatibles, Farnham, United Kingdom). PVA microspheres are easily visible because of their white (Contour SE) or blue (Bead Block) coloration. The following size ranges are currently available: 100–300, 500–700, 700–900 and 900–1200µm. PVA microspheres are easy to inject through microcatheters but are more compressible than tris-acryl microspheres. They tend to travel more distally than the irregular PVA particles or tris-acryl microspheres.


Calibrated microspheres consisting of a hydrogel core of polymethylmethacrylate with a thin coating of polyzene-F which may reduce inflammation for better biocompatibility were introduced on the market a few months ago (Embozene, Celonova, Newnan, US).


The following sizes are currently available: 40, 100, 250, 400, 500, 700, 900, 1,100 and 1,300µm. As opposed to the other types of microspheres, a tight size distribution has been chosen meaning that each syringe contains microspheres that are consistently the same size. Particles are colour-coded by particle size which may be useful to avoid inappropriate mixing, contamination of saline and contrast syringes and confirmation that optimal suspension is reached before embolization. The initial clinical experience for liver and uterine fibroid embolization has been associated with disappointing results probably due to inappropriate technique of use (size and angiographic end-point). Small sizes may travel very distally and cause non target embolization through intra-hepatic shunts or uterine artery-to-ovarian artery anastomosis.


All the particulate agents can be effective in clinical practice but there are some practical considerations to bear in mind. PVA microspheres always occlude at a more distal level than tris-acryl spheres because of different compressibility properties. In clinical practice, the interventional radiologist should consider upsizing particles when PVA or hydrogel polyzene-F microspheres are used instead of tris-acryl spheres. For uterine fibroid or bronchial artery embolization, the recommended diameter is 700–900µm (compared to 500–700µm tris-acryl microspheres) for PVA microspheres and 900 µm for hydrogel polyzene-F microspheres. Secondary redistribution seems to be more significant than with tris-acryl microspheres. Smaller particles may be selected to occlude more distal vessels and to induce tumor necrosis (liver embolization). For liver embolization, indicative size are 100–300µm or 300–500µm for tris-acryl or PVA microspheres. However, small microspheres should not be recommended in the presence of AV-shunting.


In summary, many permanent embolic particles are now available but they are not identical in their performance. Calibrated microspheres offer many potential advantages over regular PVA particles and have progressively become the first- line agent. However, among calibrated microspheres available, there are significant physical and mechanical differences that actually influence clinical outcomes. Interventional radiologists should bear in mind these differences and seek recommendations from colleagues or experts and not only from commercial brochures.



Jean-Pierre Pelage is Professor of Radiology at Hôpital Ambroise Paré, Université Paris Ouest, France. Audrey Fohlen and Vincent le Pennec are co-authors of this article. Both are from the Department of Radiology, Centre Hospitalier Universitaire de Caen, France.