A Chronic Comparison of Clinically Used Embolic Agents with GPX in Domestic Swine

Objective: Embolization agents vary in their handling, occlusion properties, and histological response. The purpose of these studies was to examine these characteristics in a chronic animal study (30, 90 days) using the preclinical GPX embolic agent and several currently available embolic devices. Additionally, an exploratory study was performed to evaluate the performance of GPX in portal vein embolization. GPX is a liquid embolic agent that does not rely on precipitation from DMSO or in situ polymerization. Instead, it is comprised of oppositely charged polymers that remain dissolved in water at high salt concentrations. Upon delivery into physiological conditions, salt diffuses away and the material transitions into a viscoelastic solid in situ. Previous short-term studies have shown reliable occlusions with minimal non-target embolization.

Methods: Standard endovascular techniques were used to introduce a microcatheter into the target site. In the chronic comparative studies, embolization was performed in a single pole of each kidney and in two distinct sites downstream from the main hepatic artery. GPX was used in a total of 15 deployments, while NBCA (n=7), Onyx-34 (n=5), PVA-200 (n=6), and coils (n=6) were used as control articles in both kidney and liver sites. Flow was monitored before and after embolization using the AFA flow scale, where 3 was a fully patent vessel and 0 represented complete embolization. Handling and performance attributes were assessed on a semi-quantitative (1-5) scale. Post-procedure blood chemistry and clinical signs were monitored. Angiograms were performed prior to termination at 30 or 90 days (5 pigs each). A pilot embolization was also performed to assess GPX performance in the portal vein. In this procedure, a percutaneous transhepatic approach was used to access the portal vein. A microcatheter was then placed in the right lobe, and GPX was delivered to embolize the vessel.

Results: A kidney embolization with GPX is depicted in Figure 1. Here, the material was selectively delivered in a vessel feeding the posterior portion of the caudal lobe. Good distal penetration was observed upon delivery. Acute and 30 day imaging showed no changes in embolic positioning or occlusion (Fig. 1 A-E). Necropsy revealed a hard infarct, which was confined to the area containing the embolic material (Fig. 1 F). Similarly, all embolizations were performed to initial stasis (AFA=0). In the physician survey, liquids rated similar in radiographic visualization and ability to occlude, but GPX achieved higher scores in ease of preparation and ease of delivery, which were statistically significant. No abnormalities in blood chemistry or adverse effects were seen from any of the devices. In the 30-day group, all sites embolized with GPX (8) and NBCA (4) remained occluded (AFA=0) with no device migration. Some partial angiographic recanalization (AFA=1 or 2) was observed with coils (3/3), Onyx (1/3) and PVA (2/3). Consistent with the angiography, kidneys from these embolizations had little to no evidence of infarct. Histopathology and 90-day data from this study will be presented. In the acute portal vein embolization (Figure 2), GPX filled and completely occluded the right lobe of the liver.

Conclusions: In established animal models, GPX and NBCA produced stable occlusions at 30 days, while partial recanalization was seen with Onyx, PVA, and coils. While GPX is a promising agent for portal vein occlusion, longer-term studies which look at both occlusion and liver hypertrophy are needed. In both studies, animals remained healthy, and the devices were well-tolerated.