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Publication Type : Patents
Thematic Areas : Nanosciences and Molecular Medicine
Publisher : Number PCT No 201641017865 (Filed) .
Source : Number PCT No 201641017865 (Filed) (2016)
Keywords : Doxorubicin; hepatocellular carcinoma; iodine-131; transarterial radioembolization; tumor retention.
Campus : Kochi
School : Center for Nanosciences
Center : Nanosciences
Department : Nanosciences and Molecular Medicine
Year : 2016
Abstract : Transarterial radioembolization (TARE) is considered the standard treatment for intermediate-stage hepatocellular carcinoma (HCC). Iodine-131 (131I)-labeled lipiodol TARE is an effective treatment for HCC but has been withdrawn due to its poor retention in tumor lesions and significant distribution in normal tissues with severe side effects. In this work, a highly tumor-specific 131I-TARE agent with long-time retention is developed by simply introducing tyrosine to poly(vinyl alcohol) (PVA) drug-eluting microbeads (Tyr-PVA-DEBs). The labeling efficiency of 131I-labeled microbeads remains above 85% in 50% serum for 31 days. Micro-single-photon emission computed tomography/computed tomography (μSPECT/CT) evidences that the 131I-labeled microbeads accumulate in the orthotopic N1S1 hepatoma of rats for 31 days following intra-arterial injection. The cumulative radiation dose per cubic centimeter of the tumor is at least 13 678-fold higher than that of normal tissues. The highly tumor-selective radiation of the 131I-labeled microbeads allows localized delivery of 345.04 ± 139.16 Gy to the tumor following a single injection dose as low as 0.2 mCi of 131I. Moreover, the 131I-labeled microbeads are loaded with doxorubicin hydrochloride (DOX) through the carboxy groups on tyrosine of the polymer. The 131I-DOX-loaded microbeads present a synergetic antitumor effect without recurrence in comparison with the microbeads labeled with 131I or loading DOX alone, attributed to the sensitization of DOX to 131I-induced ionizing radiation damage to DNA under the embolization-induced hypoxia. Our results demonstrate a high tumor retention of 131I-labeled embolic agent for low-dose transarterial radio-chemoembolization (TARCE) with a synergetic therapeutic effect on treating HCC, showing potential for clinical application.
Cite this Research Publication : Dr. Manzoor K., Harish, V., Anusha Ashokan, and Nair, S., “Non-iodinated Radiopaque Microbeads, Capable of Binding to Radioisotopes for Trans-arterial Embolization and Trans-arterial Radioembolization”, U.S. Patent PCT No 201641017865 (Filed)2016.