Paul Moroz1, Stephen K Jones, Bruce N Gray. 1. Centre for Applied Cancer Studies, University of Western Australia, 35 Stirling Highway, Crawley 6009, Perth, Western Australia, Australia. pmoroz@cyllene.uwa.edu.au
Abstract
BACKGROUND: Arterial embolization hyperthermia (AEH) consists of arterially embolizing tumors with ferromagnetic particles that generate hysteretic heating on exposure to an alternating magnetic field. It was the objective of this study to evaluate AEH using the kidney of a large animal as a tumor model. METHODS: Between 50 and 400 mg of ferromagnetic microspheres (32 microm in diameter) was arterially infused into the kidneys of three pigs. Temperature probes were inserted into renal tissue, skin, and subcutaneous fat. Each subject was then exposed to an alternating magnetic field for 5 min, while under a general anesthetic. A femoral artery catheter was used to monitor the cardiac pulse. Three days after treatment the renal tissue was chemically analyzed for iron content, which was then correlated with tissue heating rates. RESULTS: There was a linear relationship between heating rate and iron concentration (N = 18, correlation = 0.72, P < 0.001) that suggested tissue iron concentrations in the range of 1.55 to 4.05 mg/g would yield tissue heating rates of 0.5 to 1.0 degrees C/min. No temperature increases were detected in control renal tissue (N = 6). The median increase in skin temperature after 5 min of heating was 0.8 degrees C (N = 6, min = 0.7 degrees C, max = 1.3 degrees C), and that in subcutaneous fat was 1.1 degrees C (N = 6, min = 0.8 degrees C, max = 1.2 degrees C). There was no detectable stimulation of cardiac or skeletal muscle or peripheral nerves during treatment. All subjects had uneventful 3-day posttreatment survivals. CONCLUSION: This study has shown that AEH can target deep-seated, vascularized tissue in a large animal with therapeutic temperatures (> 42 degrees C), and that the treatment is safe and well tolerated. Further assessment of treatment schedules should allow for a human trial in the near future.
BACKGROUND: Arterial embolization hyperthermia (AEH) consists of arterially embolizing tumors with ferromagnetic particles that generate hysteretic heating on exposure to an alternating magnetic field. It was the objective of this study to evaluate AEH using the kidney of a large animal as a tumor model. METHODS: Between 50 and 400 mg of ferromagnetic microspheres (32 microm in diameter) was arterially infused into the kidneys of three pigs. Temperature probes were inserted into renal tissue, skin, and subcutaneous fat. Each subject was then exposed to an alternating magnetic field for 5 min, while under a general anesthetic. A femoral artery catheter was used to monitor the cardiac pulse. Three days after treatment the renal tissue was chemically analyzed for iron content, which was then correlated with tissue heating rates. RESULTS: There was a linear relationship between heating rate and iron concentration (N = 18, correlation = 0.72, P < 0.001) that suggested tissue iron concentrations in the range of 1.55 to 4.05 mg/g would yield tissue heating rates of 0.5 to 1.0 degrees C/min. No temperature increases were detected in control renal tissue (N = 6). The median increase in skin temperature after 5 min of heating was 0.8 degrees C (N = 6, min = 0.7 degrees C, max = 1.3 degrees C), and that in subcutaneous fat was 1.1 degrees C (N = 6, min = 0.8 degrees C, max = 1.2 degrees C). There was no detectable stimulation of cardiac or skeletal muscle or peripheral nerves during treatment. All subjects had uneventful 3-day posttreatment survivals. CONCLUSION: This study has shown that AEH can target deep-seated, vascularized tissue in a large animal with therapeutic temperatures (> 42 degrees C), and that the treatment is safe and well tolerated. Further assessment of treatment schedules should allow for a human trial in the near future.