A technique for accomplishing 41-42 degrees C whole body hyperthermia (WBH) in unrestrained, unanesthetized mice using a simple apparatus is reported. This method combines a radiant heat technology with monitoring of individual rectal temperatures at 10-min intervals. In 66 heating sessions, involving 116 AKR mice and a total of 619 WBH treatments, the mortality rate was less than 1%. Treatment at 41-42 degrees C for periods of up to 120 min were accomplished. Relationships of several variables of mouse temperature-time profiles were studied including (1) initial core temperature, (2) rate of heating, (3) whole body irradiation, and (4) the presence of tumor (transplanted AKR leukemia). Sham treatments produce a consistent temperature-time profile showing about a 1 degree C rise. Between-mouse variability, as well as between-treatment variability in individual animals was estimated. Thermal mapping of the device demonstrates a range from 32-38 degrees C of the air temperature in the zone with the mice to a high of 47 degrees C near to the radiant heating surface at the top of the apparatus.

Animals↗

PubMedDate not supplied

Temperature distributions, microangiographic and histopathologic correlations in normal tissue heated by ferromagnetic needles.

Rabbit hind limb musculature implanted with nine ferromagnetic nickel-copper alloy needles was inductively heated in a 120 kHz oscillating magnetic field. Rabbits were heated every third day for a total of three 30 min heating periods. Ferromagnetic needles with Curie points of 42 degrees C, 45 degrees C, and 48 degrees C were used. Fourteen days following the third heating the animals were sacrificed and the tissues processed for microangiography and histopathology. Implanted muscle heated rapidly and achieved a stable temperature within 10 min. Two weeks after heating for three 30 min heat cycles at temperatures above 47.1 degrees C, both vasculature destruction and muscle necrosis were noted. However, at temperatures below 45.5 degrees C, histopathologic and microangiographic findings were indistinguishable from unheated, implanted controls. Myocentric granuloma formation surrounding the thermoseed tracks with vascular preservation characterized tissue at a steady-state temperature between 45.5 degrees C and 47.1 degrees C. Nickel-copper alloy thermoseeds were effective at producing reproducible, localized interstitial hyperthermia. Chronic vascular and histopathologic alterations correlated closely with previous steady-state temperatures.

Angiography↗

PubMedDate not supplied

Effect of implant variables on temperatures achieved during ferromagnetic hyperthermia.

Effects of ferromagnetic implant variables on steady-state temperature were studied in both in vitro (phantom) and in vivo (rabbit hind limb musculature) models. Thermoseed implant variables included: (1) the presence and number of thermoseed sleeves; (2) variations in thermoseed alignment within the oscillating electromagnetic field; (3) generator power levels of 300 W, 600 W, and 1200 W; and (4) separation of thermoseed tracks by 0.8 cm versus 1 cm. When the thermoseeds were aligned parallel to the electromagnetic field, temperature distributions in the in vivo model using bare thermoseeds and thermoseeds encased in a single sleeve (0.1 mm wall thickness) of polyethylene tubing were statistically higher than in tests performed with thermoseeds encased in a double sleeve (0.25 mm over 0.1 mm wall thickness) of tubing (p = 0.006). Nonetheless, average steady-state temperatures above a therapeutic minimum (greater than or equal to 42 degrees C) were achieved at all generator power levels using thermoseeds encased in a double sleeve of tubing and aligned parallel to the electromagnetic field. Gross misalignment of thermoseeds with the electromagnetic field was partly compensated for by utilizing higher generator power levels. Thermoseed tracks separated by 0.8 cm and aligned parallel to the electromagnetic field yielded average steady-state temperatures that were 0.4-2.2 degrees C higher than those obtained with a thermoseed track separation of 1 cm.

Animals↗

PubMedDate not supplied

Concurrent ferromagnetic hyperthermia and 125I brachytherapy in a rabbit choroidal melanoma model.

Ferromagnetic (FM) thermoseeds and radioactive (125I) seeds were combined in an episcleral plaque to give concurrent hyperthermia and irradiation for enhanced tumour destruction. A Greene melanoma cell line was utilized to study the interaction between these treatment modalities. We attached five FM thermoseeds (with an operating temperature of 48 degrees C) in parallel with alternating rows of 125I seeds onto the inner surface of each 14 mm Silastic plaque. Plaques were centred over a 3-6 mm (diameter) intraocular melanoma in each rabbit. Some rabbits were then placed within a heating coil, and their eye tumours were warmed rapidly to therapeutic temperatures (43.6 degrees C across the tumour base) while the temperature of normal conjunctiva across the globe did not exceed 38.5 degrees C. Analysis of 49 treated eye melanomas showed 50% local tumour control at 41.7 Gy for 125I alone, whereas only 9.5 Gy were needed to give the same local control rate after 125I with concurrent FM hyperthermia. Thus, a thermal enhancement ratio of 4.4 was obtained. Hyperthermia alone gave a 20% tumour response rate, but responses were only temporary. We conclude that FM thermoseeds can be used to deliver biologically effective hyperthermia concurrently with radiation, thereby reducing the dose of radiation needed for tumour control.

Animals↗

PubMedDate not supplied

Temperature-dependent versus constant-rate blood perfusion modelling in ferromagnetic thermoseed hyperthermia: results with a model of the human prostate.

Finite-element solutions to the Pennes bioheat equation are obtained with a model of a tumour-containing, human prostate and surrounding normal tissues. Simulations of ferromagnetic hyperthermia treatments are conducted on the tissue model in which the prostate is implanted with an irregularly spaced array of thermoseeds. Several combinations of thermoseed temperatures with different Curie points are investigated. Non-uniform, constant-rate blood perfusion models are studied and compared with temperature-dependent descriptions of blood perfusion. Blood perfusions in the temperature-dependent models initially increase with tissue temperature and then decrease at higher temperatures. Simulations with temperature-dependent versus constant-rate blood perfusion models reveal significant differences in temperature distributions in and surrounding the tumour-containing prostate. Results from the simulations include differences (between temperature-dependent and constant-rate models) in (1) the percentage of normal tissue volume and tumour volume at temperatures > 42 degrees C, and (2) temperature descriptors in the tumour (subscript t) and normal (subscript n) tissues including Tmax.t, Tmin.t and Tmax.n. Isotherms and grey-scale contours in the tumour and surrounding normal tissues are presented for four simulations that model a combination of high-temperature thermoseeds. Several simulations show that Tmin.t is between 1.7 and 2.6 degrees C higher and Tmax.n is between 2.1 and 3.3 degrees C higher with a temperature-dependent versus a comparable constant-rate blood perfusion model. The same simulations reveal that the percentages of tumour volume at temperatures > 42 degrees C are between 0 and 68% higher with the temperature-dependent versus the constant-rate perfusion model over all seed combinations studied. In summary, a numerical method is presented which makes it possible to investigate temperature-dependent, continuous functions of blood perfusion in simulations of hyperthermia treatments. Simulations with this numerical method reveal that the use of constant-rate instead of temperature-dependent blood perfusion models can be a conservative approach in treatment planning of ferromagnetic hyperthermia.

Body Temperature Regulation↗

PubMedDate not supplied

Ferromagnetic hyperthermia: functional and histopathologic effects on normal rabbit ocular tissue.

Ferromagnetic (FM) hyperthermia has previously been evaluated in a rabbit tumour model of ocular melanoma. To study the effect of focal heating in normal rabbit eyes, FM seeds were implanted into a 14-mm episcleral plaque an heated to operating temperatures of 48 or 58 degrees C. Thermal induction was performed by placing rabbits in a uniform, oscillating (11 kHz) magnetic field operating at 1200 W and as H-field strength of 265 A/m. Eyes were heated for 60 min with continuous scleral temperature monitoring. Hyperthermic effects were monitored by direct opthalmic examination, fundus photography, serial electroretinography and histopathology. Intraocular temperatures were mapped with direct fiberoptic thermometry. All treatment effects were confined to the area covered by the episcleral plaque. Direct ophthalmoscopic examination revealed early retinal whitening during heat induction followed by localized exudative retinal detachments, limited to the area of the retinal surface overlying the plaque, that resolved spontaneously. Serial electroretinography was virtually indistinguishable between the 48 and 54 degrees C temperature groups. We noted a minimal alteration in a- and b-wave amplitudes with no changes in implicit times. Histopathology at 3 weeks post-treatment documented chorioretinal scarring overlying the thermal plaque treatment zone. No evidence of heamorrhage infection, cataract or scleral thinning was noted. This study documents the apparent focal containment of thermal effects with FM heating utilizing operating temperatures ad high as 54 degrees C for 60 min, and discloses no evidence of diffuse ocular toxicity.

Animals↗

PubMedDate not supplied

Hyperthermia in cancer therapy: where are we today and where are we going?

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Breast Neoplasms↗

PubMedDate not supplied

Effects of metoclopramide on the pharmacokinetics of a slow-release theophylline product.

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Adult↗