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Irinotecan Loaded in Eluting Beads: Preclinical Assessment in a Rabbit VX2 Liver Tumor Model

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Abstract

Purpose

The purpose of this study was to study the pharmacokinetics of irinotecan injected intravenously, intra-arterially, or loaded onto a delivery platform.

Material and Methods

Fifty-four New Zealand White rabbits with VX2 liver tumor, divided in 3 groups of 17 rabbits, each received irinotecan either by intravenous (IV) route, intra-arterial hepatic (IA) route, or loaded on drug-eluting beads (DEBIRI). Animals were killed at 1, 6, and 24 h. Irinotecan and SN-38 concentrations were measured at different time points in serum, tumor, and normal liver.

Results

Twelve milligrams of irinotecan were injected IV and IA, whereas 6–16.5 mg were injected loaded onto DEBIRI. Normalized serum irinotecan reached a peak of 333 ng/ml (range 198.8–502.5) for IV, 327.1 ng/ml (range 277.1–495.6) for IA, and 189.7 ng/ml (range 111.1–261.9) for DEBIRI (P < 0.001) delivery. The area-under-the-curve value from 10 to 60 min of serum irinotecan concentration was significantly lower for DEBIRI (P = 0.0009). Tumor irinotecan levels for IV, IA, and DEBIRI (in ng/200 mg of tissue followed by ranges in parentheses) were, respectively, 23.6 (0.3–24.9), 36.5 (7.7–1914.1), and 20.2 (2.9–319) at 1 h; 4.2 (1–27.9), 99.3 (46.6–159.5), and 42.1 (11.3–189) at 6 h; and 2.7 (2.5–6.9), 18.3 (1.5–369.1), and 174.4 (3.4–5147.3) at 24 h (P = 0.02). At 24 h, tumor necrosis was 25% (10–30), 60% (40–91.25), and 95% (76.25–95) for IV, IA, and DEBIRI, respectively (P = 0.03).

Conclusion

Compared with IV or IA, DEBIRI induces lower early serum levels of irinotecan, a high and prolonged intratumoral level of irinotecan, and a greater rate of tumor necrosis at 24 h. Further evaluation of the clinical benefit of DEBIRI is warranted.

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Acknowledgment

This project was supported by a grant from Biocompatibles (Farnham, UK).

Conflict of interest

None.

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Authors and Affiliations

  1. Department of Interventional Radiology, Institute Gustave Roussy, Villejuif, 94805, France

    Pramod P. Rao, Florentina Pascale, Frederic Deschamps, Christophe Teriitheau & Thierry de Baere

  2. UPRES EA 3535, Pharmacologie et Nouveaux Traitements du Cancer, Institute Gustave Roussy, Villejuif, 94805, France

    Atman Seck & Angelo Paci

  3. Service Interdépartemental de Pharmacologie et d’Analyse du Médicament, Institute Gustave Roussy, Villejuif, 94805, France

    Atman Seck & Angelo Paci

  4. Department of Biostatistics and Epidemiology, Institute Gustave Roussy, Villejuif, 94805, France

    Anne Auperin

  5. Department of Biology and Pathology, Institute Gustave Roussy, Villejuif, 94805, France

    Laurence Drouard-Troalen

  6. Department of Interventional Radiology, Centre Hospitalier Universitaire Vaudois, Lausanne, 1011, Switzerland

    Alban Denys & Pierre Bize

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  1. Pramod P. Rao
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Correspondence to Thierry de Baere.

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Rao, P.P., Pascale, F., Seck, A. et al. Irinotecan Loaded in Eluting Beads: Preclinical Assessment in a Rabbit VX2 Liver Tumor Model. Cardiovasc Intervent Radiol 35, 1448–1459 (2012). https://doi.org/10.1007/s00270-012-0343-y

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  • DOI: https://doi.org/10.1007/s00270-012-0343-y

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