TY - JOUR
T1 - Hepatic arterial embolization with doxorubicin-loaded superabsorbent polymer microspheres in a rabbit liver tumor Model
AU - Gupta, Sanjay
AU - Wright, Kenneth C.
AU - Ensor, Joe
AU - Van Pelt, Carolyn S.
AU - Dixon, Katherine A.
AU - Kundra, Vikas
N1 - Funding Information:
This work was supported in part by grants from Biosphere Medical, Inc, and the John S. Dunn Research Foundation.
PY - 2011/10
Y1 - 2011/10
N2 - Objectives The pharmacokinetic profile after hepatic arterial embolization with superabsorbent microspheres (QuadraSpheres) loaded with doxorubicin was studied. Methods Rabbits with hepatic VX2 tumors were treated with intra-arterial administration of QuadraSpheres loaded with doxorubicin, or transarterial chemoembolization (TACE) using doxorubicin, Lipiodol and Embospheres, or hepatic arterial infusion (HAI) of doxorubicin. Tumor specimens were evaluated by fluorescence microscopy, and plasma and tumor concentrations of doxorubicin were measured. Results The peak plasma concentration of doxorubicin was lower in the QuadraSphere group (309.9 ng/ml) than in the HAI (673.4 ng/ml) or TACE (360.5 ng/ml) groups, suggesting higher tumor retention in the QuadraSphere group. Intratumoral doxorubicin levels declined to negligible levels at 1 and 3 days after treatment, respectively, in the HAI and TACE groups. In the QuadraSphere groups, intratumoral doxorubicin level declined after day 1, but was still detectable at 14 days after treatment and was higher than that in the other groups at 1, 3, and 7 days. Intratumoral doxorubicin fluorescence was detected at all time points in the QuadraSphere group, but only at 1 day after treatment in the TACE group. Conclusions Hepatic arterial administration of doxorubicin- loaded QuadraSpheres enables the sustained release of doxorubicin to hepatic tumors.
AB - Objectives The pharmacokinetic profile after hepatic arterial embolization with superabsorbent microspheres (QuadraSpheres) loaded with doxorubicin was studied. Methods Rabbits with hepatic VX2 tumors were treated with intra-arterial administration of QuadraSpheres loaded with doxorubicin, or transarterial chemoembolization (TACE) using doxorubicin, Lipiodol and Embospheres, or hepatic arterial infusion (HAI) of doxorubicin. Tumor specimens were evaluated by fluorescence microscopy, and plasma and tumor concentrations of doxorubicin were measured. Results The peak plasma concentration of doxorubicin was lower in the QuadraSphere group (309.9 ng/ml) than in the HAI (673.4 ng/ml) or TACE (360.5 ng/ml) groups, suggesting higher tumor retention in the QuadraSphere group. Intratumoral doxorubicin levels declined to negligible levels at 1 and 3 days after treatment, respectively, in the HAI and TACE groups. In the QuadraSphere groups, intratumoral doxorubicin level declined after day 1, but was still detectable at 14 days after treatment and was higher than that in the other groups at 1, 3, and 7 days. Intratumoral doxorubicin fluorescence was detected at all time points in the QuadraSphere group, but only at 1 day after treatment in the TACE group. Conclusions Hepatic arterial administration of doxorubicin- loaded QuadraSpheres enables the sustained release of doxorubicin to hepatic tumors.
KW - Drug-eluting microspheres
KW - Hepatic artery embolization
KW - Pharmacokinetics
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U2 - 10.1007/s00270-011-0154-6
DO - 10.1007/s00270-011-0154-6
M3 - Article
C2 - 21479746
AN - SCOPUS:80555150829
SN - 0174-1551
VL - 34
SP - 1021
EP - 1030
JO - Cardiovascular and Interventional Radiology
JF - Cardiovascular and Interventional Radiology
IS - 5
ER -