525 - Pressure Enabled Drug Delivery (PEDD) During Delivery of Embolic Spheres Enhances Hepatic Tumor Penetration in an Oncopig Model

Purpose: To evaluate whether localized intravascular pressure elevation using Pressure-Enabled Drug Delivery (PEDD) during and after embolic sphere infusion enhances distribution and concentration of therapeutics within solid hepatic tumors in the Oncopig model. Outcomes may guide workflow parameters to improve targeted delivery.

Materials and Methods: Transgenic Oncopigs (35–55 kg) underwent induction of hepatic tumors by ex vivo oncogene activation of biopsy tissue followed by reinjection into all four liver lobes. Embospheres (100–300 µm; Merit Medical, South Jordan, UT) were conjugated with IRDye 800CW NHS Ester (Li-Cor, Lincoln, NE) as described in Jaroch et al(1). Infusions were performed via an investigational 0.038” ID microvalve infusion catheter (TriSalus Life Sciences, Westminster, CO) paired with an Aeris pressure wire (St. Jude Medical, Plymouth, MN) for continuous distal pressure measurement. Selective infusions targeted ~50% of a lobe through 1.5–2.5 mm vessels and continued until stasis, defined by the angiographic endpoints of Titano et al(2): intrahepatic collateral visualization, portal vein enhancement, or contrast seepage through the valve.

Treatment Groups:
• G1: Infusion to endpoint (n=17 tumors, n=12 animals)
• G2: Infusion to endpoint + post-embolization high-pressure ( >200 mmHg) contrast flush (n=11 tumors, n=10 animals)
• G3: Infusion interspersed with ≥2 high-pressure flushes until endpoint (n=15 tumors, n=8 animals)

Analysis: Lobes were serially sectioned (1 cm) and imaged with Near-IR (Pearl, Li-Cor). A custom Visiopharm deep learning algorithm quantified intratumoral vs. parenchymal sphere distribution.

Results: Real-time pressure monitoring allowed controlled adjustment of injection rate, reliably achieving >200 mmHg distal pressure with manual injection. A single post-embolization high-pressure flush significantly increased intratumoral sphere concentration (p≤0.05) while decreasing off-target deposition (p≤0.05). Multiple high-pressure flushes did not provide further benefit. Pressurized infusion shifted microsphere distribution from peritumoral margins (< 1 cm) into tumor cores.

Conclusion: PEDD with intraprocedural pressure monitoring enabled controlled pressure elevation during embolization. Incorporating a single high-pressure flush improved intratumoral penetration and reduced normal liver exposure, supporting pressure-modulated infusion as a workflow strategy to enhance delivery of therapeutics into solid tumors.