Histologic analysis of liver tissue following hepatic arterial infusion of ferromagnetic particles in a rabbit tumour model

• Published in: Biometals 2003-09, Vol.16 (3), p.455-464
• Main Authors: Moroz, Paul, Metcalf, Cecily, Gray, Bruce N
• Format: Article
• Language: English
• Subjects: Aggregates; Animal models; Animals; Disease Models, Animal; Embolization, Therapeutic - methods; Ferric Compounds - administration & dosage; Ferric Compounds - pharmacokinetics; Ferric Compounds - therapeutic use; Ferromagnetism; Gallbladder - metabolism; Hepatic Artery; Hysteresis; Infusion; Infusions, Intra-Arterial; Iron; Iron - analysis; Iron - metabolism; Light microscopy; Liver; Liver - metabolism; Liver - pathology; Liver Neoplasms, Experimental - therapy; Lung - metabolism; Lungs; Magnetic fields; Microspheres; Particle Size; Rabbits; Tissue Distribution; Tissues; Tumors; Tumours
• ISSN: 0966-0844; 1572-8773
• DOI: 10.1023/A:1022555431476

It is possible to arterially embolize liver tumours in small animal models with ferromagnetic particles that generate hysteretic heating on exposure to an alternating magnetic field. The aim of this study was to determine the response of hepatic tissue to arterial infusion of ferromagnetic particles. Eight rabbits containing hepatic VX2 carcinomas received a hepatic arterial infusion of ferromagnetic particles suspended in lipiodol. Four rabbits were sacrificed after 60 min to determine the acute tissue response, and the other four rabbits were sacrificed after 14 days to determine the longer-term tissue response. The tumour, normal hepatic parenchyma (NHP), lungs and gallbladder of each subject were examined using light microscopy, and chemically analysed for iron concentration. Large aggregates of particles embolized within the tumour vasculature. There was only a sparse distribution of particles in the NHP, with no acute tissue response. The tumour to NHP iron concentration ratio was 4.9. Particles also lodged in blood vessels of the gallbladder wall. Two weeks after infusion there were isolated foci of necrosis in the NHP, and macrophages were associated with particle aggregates, which were also observed within multinucleated giant cells. There was no evidence that particles embolized in the lungs. Hepatic arterial infusion of ferromagnetic particles suspended in lipiodol resulted in excellent tumour targeting with no acute tissue reaction in the NHP, and no evidence of pulmonary embolization. After 14 days there was evidence of phagocytosis of the particles in NHP, but not in the tumour tissue. However, the suspension caused multiple foci of infarction in NHP, probably due to occlusion of larger arteries.