Toshihiro Tanaka1, Hideyuki Nishiofuku2, Yasushi Hukuoka2, Takeshi Sato2, Tetsuya Masada2, Masato Takano3, Carl W Gilbert4, Chiho Obayashi3, Kimihiko Kichikawa2. 1. Department of Radiology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan. Electronic address: toshihir@bf6.so-net.ne.jp. 2. Department of Radiology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan. 3. Diagnostic Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan. 4. CeloNova BioSciences, Inc., San Antonio, Texas.
Abstract
PURPOSE: To evaluate the pharmacokinetics and antitumor efficacy of 40 μm irinotecan-loaded drug-eluting microspheres (Embozene TANDEM Microspheres; CeloNova BioSciences, Inc, San Antonio, Texas) (TANDEM-IRI). MATERIALS AND METHODS: The following three groups included eight VX2 rabbits each: group 1, full-loaded (50 mg irinotecan/1 mL TANDEM)/high-dose injection (1 mg irinotecan/kg); group 2, full-loaded (50 mg irinotecan/1 mL TANDEM)/low-dose injection (0.5 mg irinotecan/kg); and group 3, half-loaded (25 mg irinotecan/1 mL TANDEM)/low-dose injection (0.5 mg irinotecan/kg). Irinotecan and SN-38 in the plasma and tumors were measured within 72 hours. Histologic examinations were conducted on days 1, 3, and 7. RESULTS: Serum irinotecan levels remained near the maximum concentration for 180 minutes after transarterial chemoembolization; in group 1, levels were 351.4 ng/mL at 30 minutes, 329.0 ng/mL at 60 minutes, and 333.5 ng/mL at 180 minutes. The area under the curve for 0-24 hours of irinotecan in group 1 was approximately two times higher than the same value in groups 2 and 3. High irinotecan and SN-38 concentrations in the tumors were measured at 24 hours and 72 hours. After transarterial chemoembolization, levels of liver enzymes aspartate aminotransferase and alkaline phosphatase were significantly higher in group 1 compared with groups 2 and 3. Histologic findings showed microspheres had deeply penetrated into tumors. Significantly higher tumor necrosis ratios were observed in groups 1 (86.6%-90.0%) and 3 (90.0%-100%) compared with group 2 (63.3%-70%) (P = .031 and P = .016). CONCLUSIONS: Slow drug release with high drug concentration in tumors can be provided with 40 μm TANDEM-IRI. When complete arterial embolization is performed, the dose of irinotecan loaded on 40 μm TANDEM microspheres can be reduced while maintaining efficacy.
PURPOSE: To evaluate the pharmacokinetics and antitumor efficacy of 40 μm irinotecan-loaded drug-eluting microspheres (Embozene TANDEM Microspheres; CeloNova BioSciences, Inc, San Antonio, Texas) (TANDEM-IRI). MATERIALS AND METHODS: The following three groups included eight VX2 rabbits each: group 1, full-loaded (50 mg irinotecan/1 mL TANDEM)/high-dose injection (1 mg irinotecan/kg); group 2, full-loaded (50 mg irinotecan/1 mL TANDEM)/low-dose injection (0.5 mg irinotecan/kg); and group 3, half-loaded (25 mg irinotecan/1 mL TANDEM)/low-dose injection (0.5 mg irinotecan/kg). Irinotecan and SN-38 in the plasma and tumors were measured within 72 hours. Histologic examinations were conducted on days 1, 3, and 7. RESULTS: Serum irinotecan levels remained near the maximum concentration for 180 minutes after transarterial chemoembolization; in group 1, levels were 351.4 ng/mL at 30 minutes, 329.0 ng/mL at 60 minutes, and 333.5 ng/mL at 180 minutes. The area under the curve for 0-24 hours of irinotecan in group 1 was approximately two times higher than the same value in groups 2 and 3. High irinotecan and SN-38 concentrations in the tumors were measured at 24 hours and 72 hours. After transarterial chemoembolization, levels of liver enzymes aspartate aminotransferase and alkaline phosphatase were significantly higher in group 1 compared with groups 2 and 3. Histologic findings showed microspheres had deeply penetrated into tumors. Significantly higher tumor necrosis ratios were observed in groups 1 (86.6%-90.0%) and 3 (90.0%-100%) compared with group 2 (63.3%-70%) (P = .031 and P = .016). CONCLUSIONS: Slow drug release with high drug concentration in tumors can be provided with 40 μm TANDEM-IRI. When complete arterial embolization is performed, the dose of irinotecan loaded on 40 μm TANDEM microspheres can be reduced while maintaining efficacy.
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