Pulmonary artery chemoembolization in a sheep model: Evaluation of performance and safety of irinotecan eluting beads (DEB‐IRI)

Abstract

The purpose of this study was to evaluate and compare plasma pharmacokinetics, lung tissue concentration, and the potential toxicity of drug eluting beads loaded with irinotecan (DEB-IRI) in a sheep pulmonary artery chemoembolization (PACE) model. Sheep (n = 24) were embolized with DEB-IRI loaded with different doses (0, 20, 50, or 100 mg). Direct pulmonary artery (PA) injections of irinotecan were also performed at two doses (50 or 100 mg; n = 4 sheep). Irinotecan was quantified in plasma and lung tissue (liquid chromatography-fluorescence detection); pathological examination of lungs was performed 4 days or 4 weeks after PACE. Irinotecan was detected in the systemic circulation within a few minutes after PACE, for several hours in DEB-IRI 20 and DEB-IRI 50 groups, and for 24 hours for DEB-IRI 100. Both Cmax and AUC values increased significantly with dose (p = 0.0078 and p = 0.0008, respectively) after PACE. Cmax and AUC values were significantly reduced (by 80%, p = 0.0036, and by 50%, p = 0.0393, respectively) after PACE than after direct PA injection. Irinotecan was not detected in tissue 4 days after PACE. No sign of lung toxicity was observed, except a limited hemorrhagic angionecrosis seen 4 days after PACE with DEB-IRI 100. Inflammatory response on beads was moderate in all DEB-IRI groups. Compared to other routes of administration, DEB loaded with irinotecan at doses up to 100 mg was well tolerated. DEB loaded with 100 mg irinotecan seem a promising candidate for future PACE trials in patients.