In vivo evaluation of irinotecan-loaded QuadraSphere microspheres for use in chemoembolization of VX2 liver tumors.

PURPOSE: To investigate the pharmacokinetics and chemoembolization efficacy of irinotecan-loaded QuadraSphere microspheres (QSMs) in a rabbit VX2 liver tumor model. MATERIALS AND METHODS: Fourteen rabbits with VX2 liver tumors were divided into two groups. In the irinotecan-loaded QSM group (n = 7), 3 mg of QSMs (30-60 µm) containing 12 mg of irinotecan (0.6 mL; 20 mg/mL) were injected into the left hepatic artery. In the control group (hepatic arterial infusion [HAI] and QSMs; n = 7), 3 mg of QSMs suspended in ioxaglic acid were injected following a bolus injection of 0.6 mL of irinotecan solution (20 mg/mL). Sequential irinotecan, SN-38, and SN-38G concentration changes were measured in plasma within 24 hours and at 1 week and in tissues at 1 week. The VX2 tumor growth rates at 1 and 2 weeks were calculated from computed tomographic images. RESULTS: All rabbits underwent successful embolization. Plasma irinotecan, SN-38, and SN-38G concentrations in the irinotecan-loaded QSM group showed significantly sustained release compared with the control group (P = .01). Compared with the control group, the irinotecan-loaded QSM group had significantly higher irinotecan concentration in liver tumors (P = .03) and a tendency toward higher SN-38 concentration in liver tumors (P = .29). The SN-38G tissue concentrations were below the limits of quantification. The tumor growth rate was significantly lower and the tumor necrosis rate significantly higher in the irinotecan-loaded QSM group (P = .02 and P = .01, respectively). CONCLUSION: Chemoembolization via irinotecan-loaded QSMs more effectively suppresses tumor growth than chemoembolization with unloaded QSMs after HAI. A clinical feasibility study is warranted.

Embolic effects of transcatheter mesenteric arterial embolization with microspheres on the small bowel in a dog model.

PURPOSE: To determine the arterial distribution and ischemic effects of various particle sizes after transcatheter embolization of the small bowel in a dog model. MATERIALS AND METHODS: In 10 dogs, selective microsphere embolization was performed in six branches of the superior mesenteric artery. Microspheres were allocated into three size ranges (100-300 µm, 300-500 µm, and 500-700 µm) and four volume concentrations (0.625%, 1.25%, 2.5%, and 5%). For each size and volume concentration, embolization was performed of five branches at the origin of the last arcade. The distribution of microspheres and the range of ischemic changes of mucosa were evaluated histologically. Angiograms were categorized into two groups: group A, only the vasa recta nonopacified; group B, the last arcade or more proximal branches nonopacified. RESULTS: Microspheres sized 100-300 µm penetrated into intramural arteries and 500-700 µm microspheres mainly blocked arteries in the mesentery. There was a significant difference among three sizes in terms of the locations within the vasculature (P < .0001). The larger volume and the smaller size resulted in more ischemia. The range of ischemic changes among three sizes and among four volume concentrations was significantly different (P = .004 and P < .0001, respectively). The range of ischemic changes with 500-700 µm microspheres in group B was significantly greater than in group A (0% in group A vs 83% in group B, P = .001). CONCLUSIONS: In a dog model, embolization of the small bowel limited to the vasa recta with the use if 500-700 µm microspheres reduced the range of ischemic changes.