title: Transarterial sorafenib chemoembolization: preliminary study of technical feasibility in a rabbit model.
abstract: OBJECTIVE
  To test the feasibility of targeted intraarterial administration of the tyrosine kinase inhibitor chemotherapeutic agent sorafenib to inhibit embolotherapy-induced tumor angiogenesis and reduce systemic drug side effects.
  
  
  METHODS
  The left hepatic lobes of five New Zealand White rabbits (mean weight, 2.7 kg±0.2) were treated with chemoembolization with sorafenib and ethiodized oil emulsion, followed by immediate euthanasia. Postprocedure noncontrast computed tomography (CT) was used to evaluate intrahepatic chemotherapy mixture distribution. Liquid chromatography/tandem mass spectrometry (LC-MS/MS) was then used to directly measure sorafenib concentration in the treated liver tissue. Histopathologic assessment of treated left lobes was performed to identify any immediate toxic effects of the sorafenib solution.
  
  
  RESULTS
  Lobar sorafenib chemoembolization was successfully performed in all cases via the left hepatic artery. Sorafenib and ethiodized oil (mean, 6.4 mg±3.8 and 0.95 mL±0.7, respectively) were injected, and CT confirmed targeted left hepatic lobe sorafenib emulsion delivery in all cases. Corresponding LC-MS/MS analysis yielded a mean sorafenib concentration of 94.2 μg/mL±48.3 in treated left lobe samples (n = 5), significantly greater than typical therapeutic drug levels (2-10 μg/mL) achieved with oral sorafenib systemic therapy. Histopathologic assessment showed only mild or moderate nonspecific ballooning degeneration in zone 3 hepatocytes, without tissue necrosis.
  
  
  CONCLUSIONS
  Targeted transarterial sorafenib delivery is feasible and results in higher tissue drug levels than reported for systemic sorafenib therapy, without immediate histopathologic tissue toxicity. Future studies should aim to determine the utility of sorafenib chemoembolization in reducing hypoxia-induced vasculogenesis in liver tumors.
authors.affiliation: Department of Radiology and Interventional Radiology Section, University of Illinois Hospital and Health Sciences System, Chicago IL 60612, USA. rgaba@uic.edu
authors.forename: Ron C
authors.initials: RC
authors.lastname: Gaba
authors.forename: Felix Y
authors.initials: FY
authors.lastname: Yap
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Martinez
authors.forename: Yongchao
authors.initials: Y
authors.lastname: Li
authors.forename: Grace
authors.initials: G
authors.lastname: Guzman
authors.forename: Ahmad
authors.initials: A
authors.lastname: Parvinian
authors.forename: Richard B
authors.initials: RB
authors.lastname: van Breemen
authors.forename: Nishant
authors.initials: N
authors.lastname: Kumar
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D016461:Chemoembolization, Therapeutic / Q000009:adverse effects / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D004998:Ethiodized Oil / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000633:toxicity; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity; D010671:Phenylurea Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000633:toxicity; D010865:Pilot Projects; D011817:Rabbits; D000077157:Sorafenib; D014018:Tissue Distribution; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D009536:Niacinamide; D004998:Ethiodized Oil; D000077157:Sorafenib