Arterial Embolization Hyperthermia Research Articles

Magnetic Nanomaterials for Arterial Embolization and Hyperthermia of Parenchymal Organs Tumors: A Review.

Magnetic hyperthermia (MH), proposed by R. K. Gilchrist in the middle of the last century as local hyperthermia, has nowadays become a recognized method for minimally invasive treatment of oncological diseases in combination with chemotherapy (ChT) and radiotherapy (RT). One type of MH is arterial embolization hyperthermia (AEH), intended for the presurgical treatment of primary inoperable and metastasized solid tumors of parenchymal organs. This method is based on hyperthermia after transcatheter arterial embolization of the tumor’s vascular system with a mixture of magnetic particles and embolic agents. An important advantage of AEH lies in the double effect of embolotherapy, which blocks blood flow in the tumor, and MH, which eradicates cancer cells. Consequently, only the tumor undergoes thermal destruction. This review introduces the progress in the development of polymeric magnetic materials for application in AEH.

Injectable hydrogel cross-linked by quadruple hydrogen bonding for drug encapsulation and delivery

Maghemite nanoparticle based silicone composite for application in arterial embolization hyperthermia is developed. It possesses embolization ability, high heating efficiency in alternating magnetic fields and radiopaque property. The initial components of the composite are selected so that the material stays liquid for 20 min, providing the opportunity for transcatheter transportation and filling of the tumour vascular system. After this induction period the viscosity increases rapidly and soft embolus is formed which is able to occlude the tumour blood vessels. The composite is thermally stable up to 225 °C, displays rubber-elastic properties and has a thermal expansion coefficient higher than that of blood. Maghemite nanoparticles uniformly distributed in the composite provide its rapid heating (tens of °C min− 1) due to Neel magnetization relaxation. Required X-ray contrast of composite is achieved by addition of potassium iodide.

Stainless Steel Hollow Microspheres for Arterial Embolization Hyperthermia

To find a novel microscaled mediator suitable for arterial embolization hyperthermia (AEH). Stainless steel microspheres including both hollow (H1) and solid ones (S1) were produced with dispersing molten steel stream by water jet. Theoretically analyzing the power absorption of them in alternating magnetic field revealed that larger size and smaller permeability led to more heat generation. Higher field intensity and frequency also improved the heating power. Given the same condition, heating power per unit mass was greater in hollow microsphere than solid one. Microscopic observations of H1 and S1 were conducted along with particle size distribution, magnetization curve and heating power measurement. In vivo heating test, in vitro hyperthermia test and in vitro biocompatibility test were conducted for the finally selected mediator H1. The measured heating power of H1 and S1 met the theoretical values in low intensity field, but was considerably below expectation in strong field. Power density of H1 was clearly greater than that of S1 as theoretically predicted. The temperature of a rabbit ear in magnetic field injected with H1 maintained 50 °C for 10 min. In vitro hyperthermia test showed its outstanding treatment effectiveness for cancer cells. Cytotoxicity of H1 was categorized as Grade I, which is regarded as no cytotoxicity. Stainless steel hollow microsphere H1 was a promising mediator for AEH for its high efficiency in heating tumor region and killing cancer cells as well as good biocompatibility.

Maghemite based silicone composite for arterial embolization hyperthermia.

Maghemite nanoparticle based silicone composite for application in arterial embolization hyperthermia is developed. It possesses embolization ability, high heating efficiency in alternating magnetic fields and radiopaque property. The initial components of the composite are selected so that the material stays liquid for 20min, providing the opportunity for transcatheter transportation and filling of the tumour vascular system. After this induction period the viscosity increases rapidly and soft embolus is formed which is able to occlude the tumour blood vessels. The composite is thermally stable up to 225°C, displays rubber-elastic properties and has a thermal expansion coefficient higher than that of blood. Maghemite nanoparticles uniformly distributed in the composite provide its rapid heating (tens of °Cmin(-1)) due to Neel magnetization relaxation. Required X-ray contrast of composite is achieved by addition of potassium iodide.

Preparation and Characterization of Fe3O4/Ethiodized‐oil Magnetic Fluids Used in Arterial Embolization Hyperthermia

AbstractFe3O4 nanoparticles (NPs) were prepared by the co‐precipitation of Fe3+ and Fe2+ with ammonium hydroxide, and were modified by four different surfactants. The modified Fe3O4 NPs were characterized by Fourier transform infrared spectroscopy, X‐ray powder diffraction, transmission electron microscopy and vibrating sample magnetometer. Then, the modified Fe3O4 NPs were dispersed in ethiodized‐oil by mechanical agitation and ultrasonic vibration to obtain stable Fe3O4/ethiodized‐oil magnetic fluids (MFs). The magnetic properties and rheological properties of the MFs were measured using a Gouy magnetic balance and a rotational rheometer, respectively. The saturation magnetization of the Fe3O4 modified by oleic acid was 52.1 emu/g. Furthermore, the result showed that the inductive heating effect of oleic acid stabilized Fe3O4/ethiodized‐oil MF was remarkable and it only took 650 s for the temperature rising from 25°C to 65°C. The specific absorption rate of the MF was 50.16 W/(g of Fe). It had a potential application in arterial embolization hyperthermia.

Arterial Embolization Hyperthermia Using As2O3 Nanoparticles in VX2 Carcinoma–Induced Liver Tumors

BackgroundCombination therapy for arterial embolization hyperthermia (AEH) with arsenic trioxide (As2O3) nanoparticles (ATONs) is a novel treatment for solid malignancies. This study was performed to evaluate the feasibility and therapeutic effect of AEH with As2O3 nanoparticles in a rabbit liver cancer model. The protocol was approved by our institutional animal use committee.Methodology/Principal FindingsIn total, 60 VX2 liver-tumor-bearing rabbits were randomly assigned to five groups (n = 12/group) and received AEH with ATONs (Group 1), hepatic arterial embolization with ATONs (Group 2), lipiodol (Group 3), or saline (Group 4), on day 14 after tumor implantation. Twelve rabbits that received AEH with ATONs were prepared for temperature measurements, and were defined as Group 5. Computed tomography was used to measure the tumors' longest dimension, and evaluation was performed according to the Response Evaluation Criteria in Solid Tumors. Hepatic toxicity, tumor necrosis rate, vascular endothelial growth factor level, and microvessel density were determined. Survival rates were measured using the Kaplan-Meier method. The therapeutic temperature (42.5°C) was obtained in Group 5. Hepatotoxicity reactions occurred but were transient in all groups. Tumor growth was delayed and survival was prolonged in Group 1 (treated with AEH and ATONs). Plasma and tumor vascular endothelial growth factor and microvessel density were significantly inhibited in Group 1, while tumor necrosis rates were markedly enhanced compared with those in the control groups.ConclusionsATON-based AEH is a safe and effective treatment that can be targeted at liver tumors using the dual effects of hyperthermia and chemotherapy. This therapy can delay tumor growth and noticeably inhibit tumor angiogenesis.

Three-Dimensional Model for Determining Inhomogeneous Thermal Dosage in a Liver Tumor During Arterial Embolization Hyperthermia Incorporating Magnetic Nanoparticles

Hyperthermia treatment incorporating magnetic nanoparticles (MNPs) is a hopeful therapy for cancers. Acquiring information about the MNPs' deposition in tumor tissues and modeling magnetic heating <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">in</i> <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">vivo</i> are essential for successful treatment. In this paper, we discuss the inhomogeneous heat generation by MNPs distributed heterogeneously in a liver tumor during arterial embolization hyperthermia (AEH) treatments. In order to more accurately simulate the temperature elevation for an AEH treatment plan, we conducted the following experiments. First, we detected the distribution of magnetic field intensity in the aperture of a ferrite-core applicator. We found that attenuation of the magnetic field focuses mainly on the vertical distance of the aperture, which makes MNPs in tissues have different power loss along the lognitudinal axis. Second, we prepared 20 nm monodisperse lipiodol-soluble MNPs and injected super-selectively through the micro-catheter into the arteries of a rabbit with a VX-2 liver tumor. By histological cuts of the investigated specimen, as well as computed tomography (CT), we found MNPs mainly concentrated on the tumor periphery. Last, from the experimental information, we established a new model for simulating the increasing temperature in the liver tumor based on our inhomogeneous interior-heat-source analysis (IIA). We also compared the simulated results with the two types of homogeneous models. The results showed that IIA gives significantly different results from those for a homogeneous model and thus is preferable when an accurate treatment plan is required during AEH.

Magnetic targeting hyperthermia and its application in tumor therapy

Magnetic targeting hyperthermia (MTH), including arterial embolization hyperthermia, direct injection hyperthermia and intracellular hyperthermia, is a novel strategy against tumor in current. Targeting tumor therapy strategy involves the conjunction of biological materials to the magnetic materials, temperature measurement and control technique. It has been utilized in anti-tumor treatment of various animal tumor models, and gotten satisfactory effect in the clinical trials. Key words: Neoplasms; Magnetics; Hyperthermia, induced

Measurement of Specific Absorption Rate and Thermal Simulation for Arterial Embolization Hyperthermia in the Maghemite-Gelled Model

Theoretical models are designed to be applied in hyperthermia treatment planning and to help optimize the surgical treatment procedures. However, it is difficult to obtain every physical parameter of the magnetic field in the living tissue in detail, which is necessary for the calculation. We therefore investigated the simulation of thermal distribution in arterial embolization hyperthermia (AEH) stimulated by the external ferrite-core applicator, and measured specific absorption rate (SAR) of magnetic nanoparticles in the maghemtite-gelled composite model. We used fiber optic temperature sensors (FOTS) to measure the values of SAR, which depend on the microstructure and sizes of particles and the intensity and frequency of external ac magnetic field. Detailed tests indicated that the attenuation of magnetic field was mainly focused on the vertical distance in the aperture of the apparatus. We built a simplified cylindrical phantom containing maghemite particles of 20 nm for thermal field simulation on the basis of SAR measurement. The results of simulation indicated that temperature elevation, induced by nanoparticles inside tumors under ac magnetic field, was dose-dependent. The temperature data acquired from the experiment were compatible with the theoretical results, which demonstrated that the current model considering the inhomogenous heat generation could provide accurate and reliable simulation results and a theoretical and technical basis for controlling temperature during AEH therapy

Hepatic clearance of arterially infused ferromagnetic particles

Objective : Arterial embolization hyperthermia (AEH) consists of arterially embolizing tumours with ferromagnetic particles that generate hysteretic heating on exposure to an alternating magnetic field. It was the objective of this study to determine if such particles are cleared from the liver. Method : A lobe of normal liver in three pigs was arterially embolized with 300 mg of n -Fe 2 O 3 particles (150 nm) suspended in lipiodol. The same liver lobe of three other pigs was embolized with 300 mg of ferromagnetic polymer matrix-encapsulated microspheres (32 µm) suspended in 1% tween-water. Samples of liver and blood were obtained before infusion, and at 60 min and 28 days after arterial infusion. At 28 days, samples of lung and other abdominal viscera were also obtained. The tissue samples were chemically analysed for iron content, and submitted to histopathological examination. Results : There was no significant reduction in the hepatic iron concentration in either treatment group 28 days after infusion. Both types of particles illicited an immunogenic response and were extensively phagocytosed in the liver. The particle/lipiodol suspension caused extensive necrosis of liver, while the microsphere/tween-water suspension was well tolerated. Small amounts of both types of ferromagnetic particles embolized in the lungs, but there was no evidence of embolization into other organs. There were no haematological or biochemical changes and all subjects experienced uneventful 28-day survivals. Conclusion : This study has shown that, although arterially infused ferromagnetic particles were extensively phagocytosed, there was no significant hepatic clearance 28 days after infusion. It also determined that the suspension of 150 nm ferromagnetic particles in lipiodol was too vaso-occlusive for use in hepatic tissue. However, the suspension of 32 µm microspheres containing ferromagnetic particles in tween-water was safe and well tolerated.

Tumor response to arterial embolization hyperthermia and direct injection hyperthermia in a rabbit liver tumor model.

It is possible to arterially embolize or directly inject liver tumors in small animal models with ferromagnetic particles that generate hysteretic heating on exposure to an alternating magnetic field. The objective of this study was to compare the response of liver tumors to arterial embolization hyperthermia (AEH) and direct injection hyperthermia (DIH). Ten rabbits containing experimental hepatic tumors were treated with AEH, and a second group of ten rabbits were treated with DIH. The tumors of both groups were heated to 43 degrees to 50 degrees C for 20 minutes. Tumor response, which was determined by measuring change in tumor volume and by comparison of tumor mass after treatment with the mass of untreated control tumors of the same age, was assessed 14 days after treatment. All tumors treated with AEH decreased in volume by 50% to 94% (P = 0.005), and their average mass (median 1.73 gm) was significantly less than that of untreated control tumors (median 8.01 gm, n = 20; P < 0.001). Three of the treated tumors were completely necrotic, while the remainder were at least 80% necrotic. Nine of the ten tumors treated with DIH increased in volume by at least 143% (P = 0.01), and their average mass (median 5.68 gm) was not significantly different from that of the untreated control tumors (P = 0.56). These results indicate that AEH is more effective than DIH at moderately elevated temperatures. This is probably because the more widespread particle distribution that can be achieved using arterial embolization results in more extensive and complete treatment of the tumor.

Arterial Embolization Hyperthermia in Porcine Renal Tissue

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 μm 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°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°C (N = 6, min = 0.7°C, max = 1.3°C), and that in subcutaneous fat was 1.1°C (N = 6, min = 0.8°C, max = 1.2°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°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.

Arterial embolization hyperthermia: hepatic iron particle distribution and its potential determination by magnetic resonance imaging

Arterial embolization hyperthermia (AEH) consists of arterially embolizing liver tumours with ferromagnetic particles that generate hysteretic heating on exposure to an alternating magnetic field. A critical component of AEH is the concentration and distribution of ferromagnetic particles in the normal hepatic parenchyma (NHP), as well as in the tumour tissue. If the distribution of particles in NHP is heterogeneous, with areas of high concentration, then unwanted areas of necrosis may result during AEH. Using an in vivo rabbit liver tumour model, this study showed that hepatic arterial infusion of ferromagnetic particles does indeed result in a heterogeneous distribution of iron in NHP. The radiological technique of magnetic resonance imaging (MRI) was then evaluated as a potential tool for non-invasively and prospectively determining the concentration and distribution of particles within the hepatic tumour and NHP following hepatic arterial infusion. A preliminary in vitro experiment showed that although the concentration of iron within the tumour tissue (1.92–3.50 mg of iron per gram of tissue) was too great to measure, MRI was able to accurately determine the lower iron concentration (0.10–0.53 mg of iron per gram of tissue) in NHP. Further work is needed to evaluate MRI under in vivo conditions. If successful, MRI could become an important component of an emerging novel treatment for advanced hepatic malignancies.

Magnetically mediated hyperthermia: current status and future directions

The use of hyperthermia in the treatment of cancers is appealing because, as a physical therapy, hyperthermia would have far fewer restrictive side effects than chemotherapy and radiotherapy, and it could be used in combination with these therapies. However, the currently available modalities of hyperthermia are often limited by their inability to selectively target tumour tissue and, hence, they carry a high risk of collateral organ damage or they deposit heat in a very localized manner which can result in under-treatment of a tumour. Magnetically mediated hyperthermia (MMH) has the potential to address these shortcomings. MMH consists of the localization of magnetic particles or seeds within tumour tissue followed by exposure to an externally applied alternating magnetic field to cause them to heat. Since this concept was introduced (over 40 years ago), MMH has evolved into four general sub-classes: arterial embolization hyperthermia (AEH), direct injection hyperthermia (DIH), intracellular hyperthermia (IH) and interstitial implant hyperthermia (IIH). It is the purpose of this article to review these four sub-classes in terms of experimental or clinical results, advantages, limitations and current status.

Trans-catheter hepatic arterial injection of lipiodol soluble anti-cancer agent SMANCS and ADR suspension in lipiodol combined with arterial embolization and local hyperthermia for treatment of hepatocellular carcinoma

The clinical effect and safety of Lp-TAE alone and combined with radiofrequency (RF) capacitive hyperthermia (HT) were evaluated in 20 patients with hepatocellular carcinoma (HCC) associated with cirrhosis of the liver. After the oily carcinostatic agents were administered by Lp-TAE, HT, at a temperature of greater than 42.5 degrees C, was induced for 40 min, twice a week by an RF of 8 MHz for a total of 10 to 38 times. The response rate was 40% in the 10 cases that were treated with Lp-TAE combined with HT and 20% in the 10 cases that were treated with Lp-TAE. The patients who were treated with Lp-TAE combined with HT had a tendency to have better survival rates than those of the Lp-TAE group (p less than 0.099). The main side-effects of Lp-TAE combined with HT were low-grade fever, localized pain, myelo-suppression and liver dysfunction, but these were transient and eventually disappeared.