Intra-arterial instillation of microencapsulated, Ifosfamide-activating cells in the pig pancreas for chemotherapeutic targeting.
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.
Kröger
Jens-Christian
JC
Department of Diagnostic Radiology, University of Rostock, Germany.
Benz
Stefan
S
Hoffmeyer
Anne
A
Bago
Zoltan
Z
Bergmeister
Helga
H
Günzburg
Walter H
WH
Karle
Peter
P
Klöppel
Günter
G
Losert
Udo
U
Müller
Petra
P
Nizze
Horst
H
Obermaier
Robert
R
Probst
Alexander
A
Renner
Matthias
M
Saller
Robert
R
Salmons
Brian
B
Schwendenwein
Ilse
I
von Rombs
Kerstin
K
Wiessner
Reiko
R
Wagner
Thomas
T
Hauenstein
Karlheinz
K
Löhr
Matthias
M
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
D018906:Antineoplastic Agents, Alkylating; D002214:Capsules; D019362:Cytochrome P-450 CYP2B1; D007069:Ifosfamide