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

OBJECTIVE

To investigate the pharmacokinetics and chemoembolization efficacy of irinotecan-loaded QuadraSphere microspheres (QSMs) in a rabbit VX2 liver tumor model.

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).

CONCLUSIONS

Chemoembolization via irinotecan-loaded QSMs more effectively suppresses tumor growth than chemoembolization with unloaded QSMs after HAI. A clinical feasibility study is warranted.