title: Pharmacokinetics and antitumor efficacy of chemoembolization using 40 µm irinotecan-loaded microspheres in a rabbit liver tumor model.
abstract: OBJECTIVE
  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).
  
  
  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.
authors.affiliation: Department of Radiology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan. Electronic address: toshihir@bf6.so-net.ne.jp.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Radiology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Nishiofuku
authors.affiliation: Department of Radiology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hukuoka
authors.affiliation: Department of Radiology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Radiology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Masada
authors.affiliation: Diagnostic Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Takano
authors.affiliation: CeloNova BioSciences, Inc., San Antonio, Texas.
authors.forename: Carl W
authors.initials: CW
authors.lastname: Gilbert
authors.affiliation: Diagnostic Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan.
authors.forename: Chiho
authors.initials: C
authors.lastname: Obayashi
authors.affiliation: Department of Radiology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan.
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Kichikawa
mesh_terms: D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001219:Aspartate Aminotransferases / Q000097:blood; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D016461:Chemoembolization, Therapeutic; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D000077146:Irinotecan; D008114:Liver Neoplasms, Experimental / Q000098:blood supply / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008863:Microspheres; D009336:Necrosis; D010316:Particle Size; D011817:Rabbits
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D000077146:Irinotecan; D001219:Aspartate Aminotransferases; D000469:Alkaline Phosphatase; D002166:Camptothecin