Intra-arterial instillation of microencapsulated, ifosfamide-activating cells in the pig pancreas for chemotherapeutic targeting

• Published in: Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] 2003, Vol.3 (1), p.55-63
• Main Authors: Kröger, Jens-Christian, Benz, Stefan, Hoffmeyer, Anne, Bago, Zoltan, Bergmeister, Helga, Günzburg, Walter H., Karle, Peter, Klöppel, Günter, Losert, Udo, Müller, Petra, Nizze, Horst, Obermaier, Robert, Probst, Alexander, Renner, Matthias, Saller, Robert, Salmons, Brian, Schwendenwein, Ilse, von Rombs, Kerstin, Wiessner, Reiko, Wagner, Thomas, Hauenstein, Karlheinz, Löhr, Matthias
• Format: Article
• Language: English
• Subjects: Angiographical targeting; Angiography; Animals; Antineoplastic Agents, Alkylating - administration & dosage; Antineoplastic Agents, Alkylating - blood; Antineoplastic Agents, Alkylating - metabolism; Antineoplastic Agents, Alkylating - pharmacokinetics; Capsules; Cell Line; Cell Transplantation - methods; Chemotherapy; CYP2B1; Cytochrome P-450 CYP2B1 - biosynthesis; Cytochrome P-450 CYP2B1 - genetics; Feasibility Studies; Femoral Artery; Genetic Engineering; Humans; Ifosfamide; Ifosfamide - administration & dosage; Ifosfamide - blood; Ifosfamide - metabolism; Ifosfamide - pharmacokinetics; In Vitro Techniques; Instillation, Drug; Intra-arterial application; Microspheres; Original Paper; Pancreas - blood supply; Pancreas - drug effects; Pancreas - pathology; Pancreatic carcinoma; Pig pancreas; Regional Blood Flow - drug effects; Splenic Artery - diagnostic imaging; Swine
• ISSN: 1424-3903; 1424-3911
• DOI: 10.1159/000069147

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. Material and 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. Conclusion: 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.