title: Intra-arterial instillation of microencapsulated, Ifosfamide-activating cells in the pig pancreas for chemotherapeutic targeting.
abstract: BACKGROUND
  The therapeutic efficacy of intratumoral instillation of genetically engineered, CYP2B1-expressing, microencapsulated cells in combination with ifosfamide had been previously demonstrated in xenografted human pancreatic ductal carcinomas [Gene Ther 1998;5:1070-1078]. Prior to a clinical study, the feasibility of an intra-arterial application of microencapsulated cells to the pancreas and its consequences to the organ had to be evaluated.
  
  
  METHODS
  Microencapsulated, CYP2B1-producing cells were instilled both in vivo (transfemoral angiographical access) and in vitro (perfusion model) in the splenic lobe of the pig pancreas. In vivo, animals were monitored clinically for 7 days, then treated with ifosfamide and sacrificed. In vitro, ifosfamide was administered intra-arterially.
  
  
  RESULTS
  In all animals, 100 microcapsules could be instilled safely via the femoral route without clinical, biochemical or histological signs of pancreatitis. Histological examination revealed partial obstruction of small arteries by the capsules, without causing any parenchymal damage. In vitro, instillation reduced blood flow by half. Ifosfamide, also in combination with the capsules, did not add any damage to the pancreas.
  
  
  CONCLUSIONS
  Intra-arterial instillation of microencapsulated cells to the pig pancreas is feasible and safe. Neither pancreatitis, foreign body reactions nor circulatory disturbances were observed. Clinical application of this genetically enhanced chemotherapeutic method seems possible.
authors.affiliation: Department of Diagnostic Radiology, University of Rostock, Germany.
authors.forename: Jens-Christian
authors.initials: JC
authors.lastname: Kröger
authors.forename: Stefan
authors.initials: S
authors.lastname: Benz
authors.forename: Anne
authors.initials: A
authors.lastname: Hoffmeyer
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Bago
authors.forename: Helga
authors.initials: H
authors.lastname: Bergmeister
authors.forename: Walter H
authors.initials: WH
authors.lastname: Günzburg
authors.forename: Peter
authors.initials: P
authors.lastname: Karle
authors.forename: Günter
authors.initials: G
authors.lastname: Klöppel
authors.forename: Udo
authors.initials: U
authors.lastname: Losert
authors.forename: Petra
authors.initials: P
authors.lastname: Müller
authors.forename: Horst
authors.initials: H
authors.lastname: Nizze
authors.forename: Robert
authors.initials: R
authors.lastname: Obermaier
authors.forename: Alexander
authors.initials: A
authors.lastname: Probst
authors.forename: Matthias
authors.initials: M
authors.lastname: Renner
authors.forename: Robert
authors.initials: R
authors.lastname: Saller
authors.forename: Brian
authors.initials: B
authors.lastname: Salmons
authors.forename: Ilse
authors.initials: I
authors.lastname: Schwendenwein
authors.forename: Kerstin
authors.initials: K
authors.lastname: von Rombs
authors.forename: Reiko
authors.initials: R
authors.lastname: Wiessner
authors.forename: Thomas
authors.initials: T
authors.lastname: Wagner
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Hauenstein
authors.forename: Matthias
authors.initials: M
authors.lastname: Löhr
mesh_terms: D000792:Angiography; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D002214:Capsules; D002460:Cell Line; D017690:Cell Transplantation / Q000379:methods*; D019362:Cytochrome P-450 CYP2B1 / Q000096:biosynthesis / Q000235:genetics; D005240:Feasibility Studies; D005263:Femoral Artery; D005818:Genetic Engineering; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D007322:Instillation, Drug; D008863:Microspheres; D010179:Pancreas / Q000098:blood supply* / Q000187:drug effects* / Q000473:pathology; D012039:Regional Blood Flow / Q000187:drug effects; D013157:Splenic Artery / Q000000981:diagnostic imaging; D013552:Swine
chemical_list: D018906:Antineoplastic Agents, Alkylating; D002214:Capsules; D019362:Cytochrome P-450 CYP2B1; D007069:Ifosfamide