Moroz Paul, Metcalf Cecily, Gray Bruce N
Centre for Applied Cancer Studies, The University of Western Australia, Nedlands, 6000, Perth, Western Australia.
Biometals. 2003 Sep;16(3):455-64. 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.
在小动物模型中,使用在交变磁场作用下产生滞后发热的铁磁性颗粒对肝肿瘤进行动脉栓塞是可行的。本研究的目的是确定肝组织对动脉注入铁磁性颗粒的反应。八只患有肝VX2癌的兔子接受了肝动脉注入悬浮在碘油中的铁磁性颗粒。60分钟后处死四只兔子以确定急性组织反应,另外四只兔子在14天后处死以确定长期组织反应。对每个受试者的肿瘤、正常肝实质(NHP)、肺和胆囊进行光学显微镜检查,并对铁浓度进行化学分析。大量颗粒聚集体栓塞在肿瘤血管内。NHP中只有稀疏的颗粒分布,无急性组织反应。肿瘤与NHP的铁浓度比为4.9。颗粒也沉积在胆囊壁血管中。注入两周后,NHP中有散在的坏死灶,巨噬细胞与颗粒聚集体相关,在多核巨细胞内也观察到颗粒聚集体。没有证据表明颗粒栓塞在肺中。肝动脉注入悬浮在碘油中的铁磁性颗粒可实现良好的肿瘤靶向,NHP中无急性组织反应,也没有肺栓塞的证据。14天后,有证据表明NHP中有颗粒被吞噬,但肿瘤组织中没有。然而,该混悬液导致NHP中出现多个梗死灶,可能是由于较大动脉的阻塞所致。