Targeting liver tumors with hyperthermia: Ferromagnetic embolization in a rabbit liver tumor model

Moroz, Paul; Jones, Stephen; Winter, J G; Gray, Bruce N.

doi:10.1002/jso.1118

Cited by 105 publications

(70 citation statements)

References 42 publications

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“…3 Intratumor distribution of magnetic fluids by vascular administration has been studied in several neoplastic models induced by direct inoculation of tumor cells into the liver. 3,20,21 In general, these studies are based on the fact that the vascular supply of the neoplastic tissue comes exclusively via the hepatic artery. 3,22 This characteristic would allow the selective deposition of nanoparticles into tumors, thereby avoiding lesions in healthy liver parenchyma.…”

Section: Discussionmentioning

confidence: 99%

Study of the intra-arterial distribution of Fe3O4 nanoparticles in a model of colorectal neoplasm induced in rat liver by MRI and spectrometry

Garcı́a-Alonso¹,

Plazaola²,

Insausti³

et al. 2012

IJN

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Purpose: To evaluate, in an experimental model, the reliability of MRI for determining whether a higher iron concentration was obtained in tumor tissue than in normal liver parenchyma after intra-arterial administration of Fe 3 O 4 lipophilic nanoparticles. Materials and methods: WAG/RijCrl rats were inoculated in the left hepatic lobe with 25,000 syngeneic CC-531 colon adenocarcinoma cells, after which they were randomized into two groups: control (CG) and infused (IG). After confirming tumor induction, the IG rats received intra-arterial suspensions of Fe 3 O 4 nanoparticles (2.6 mg) in Lipiodol ® (0.15 mL). To calculate the iron concentration, [Fe], in the tumor and liver tissues of both groups of rats, measurements of signal intensity from the tumors, healthy liver tissue, and paravertebral muscles were made on a 1.5T MRI system in gradient-echo DP* and T2*-weighted sequences. In addition, samples were collected to quantify the [Fe] by inductively coupled plasma-mass spectrometry (ICP-MS), as well as for histological analysis. Statistical analysis was performed with non-parametric tests, and Bland-Altman plots were produced; P values ,0.05 were considered significant. , respectively, in the hepatic tissue. In the IG rats (n = 19), the values obtained by MRI and ICP-MS were 148.9 µmol ⋅ g −1 and 9.4 µmol ⋅ g −1, respectively, in the tumors, and 115.3 µmol ⋅ g −1 and 11.6 µmol ⋅ g −1 , respectively, in the healthy liver tissue. The IG results revealed a clear disagreement between MRI and ICP-MS. In the comparative analysis between the groups regarding the [Fe] values obtained by ICP-MS, significant differences were found for the tumor samples (P , 0.001), but not for the hepatic tissue (P = 0.92). Under microscopy, scattered intravascular deposits of nanoparticles were observed, especially in the tumors.Conclusion: ICP-MS demonstrated significant uptake of exogenous iron in tumor tissue. MRI was useful for quantifying the [Fe] in the different tissues in the CG animals, but not in the IG animals. Although the irregular distribution of nanoparticles caused an important bias in the measurements obtained by MRI, the relative increase in iron content inside the tumor was suggested.

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Section: Discussionmentioning

confidence: 99%

Study of the intra-arterial distribution of Fe3O4 nanoparticles in a model of colorectal neoplasm induced in rat liver by MRI and spectrometry

Garcı́a-Alonso¹,

Plazaola²,

Insausti³

et al. 2012

IJN

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“…24) Targeting hyperthermia using magnetite via blood vessels has been used for liver and renal carcinoma. 25,26) To our knowledge, this is the first report of hyperthermia using magnetite injected non-invasively via lymph vessels for the treatment of cervical lymph node metastasis. In conclusion, MLs injected into the tongue can target cervical lymph node metastases of tongue cancer and generate therapeutically effective temperatures in conjunction with AMF irradiation in a small animal model.…”

Section: )mentioning

confidence: 91%

Selective hyperthermia using magnetoliposomes to target cervical lymph node metastasis in a rabbit tongue tumor model

et al. 2003

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The effect of hyperthermia on cervical lymph node metastasis of VX7 tongue cancer in female Japanese white rabbits was investigated. Magnetoliposomes (MLs) with a neutral surface charge and a size of 94.1 nm were used as heating mediators. MLs were injected into the tongue 20 days after tumor transplantation, and we examined whether they reached the metastatic deep cervical lymph node. The highest magnetite concentration 24 h after ML injection was detected in the lymph node, followed by tongue, spleen, blood, and liver. Rabbits were separated into three groups: group I as the control; group II with ML injection alone; and group III with ML injection and hyperthermia 24 h after ML injection, generated by applying an alternating magnetic field (118 kHz, 384 Oe) to the neck region. The hyperthermic effect was evaluated in terms of the percentage of necrosis in proportion to the metastatic tumor and the apoptotic index (AI), defined as the ratio of TUNEL-positive cells. The temperature of lymph nodes in group III reached over 44°C. The mean area of necrosis in group III was 58.0%, which was significantly higher than that in group I (19.6%) or group II (20.4%). The AI in group III was 22.9%, significantly higher than in group I (1.67%) or II (1.42%). The difference between group I and II was not statistically significant. he presence of cervical lymph node metastasis of head and neck cancer is a negative prognostic factor. The major modalities presently available for treating highly advanced head and neck cancer include surgery, radiotherapy and chemotherapy, but even the combination of all three modalities has limited efficacy. No therapeutic method has been established for cases with cervical lymph node metastasis, and the results of treatments used to date have been unsatisfactory: even with intensive radiochemothermotherapy, more than 60% of these patients die as a result of uncontrollable local progressions of the cervical lymph node metastases.1) The use of hyperthermia has generally been confined to cervical lymph node metastasis accessible with a radiofrequency system using external applicators, in combination with synergistic chemoradiotherapy. We earlier concluded that the goal of preoperative thermochemoradiotherapy is to reduce cervical lymph node metastases to surgically treatable size, and complete removal at surgery remains a critical part of treatment.2) Hyperthermia is appealing because it is a physical treatment with fewer side effects than chemotherapy and radiotherapy, and repeated treatments should be feasible without concern for cumulative toxic side effects. However, almost all recent hyperthermia methods heat not only the tumor, but also normal tissue, which is damaged by nonspecific heating. A new method to heat only the tumor and a new heating mediator for this purpose are needed. Some researchers have been investigating submicron magnetic particles as heating mediators. [3][4][5] We have recently developed magnetite particles with a cationic liposomal membrane, 'magnetite cationic liposome...

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“…Potential advantages are a very selective local heat deposition and a more homogeneous tissue temperature distribution compared to other hyperthermia techniques. Several preclinical studies on arterial embolization hyperthermia of liver cancer used lipiodol suspensions [21][22][23][24][25]. Moroz and co-workers concluded from their data that for a given tumor iron concentration, larger tumors heat at a greater rate than small tumors due to the poorer tissue cooling and better heat conduction in the necrotic regions of large tumors [22].…”

Section: Introductionmentioning

confidence: 99%

Clinical applications of magnetic nanoparticles for hyperthermia

Thiesen¹,

Jordan

2008

International Journal of Hyperthermia

745

556

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Magnetic fluids are increasingly used for clinical applications such as drug delivery, magnetic resonance imaging and magnetic fluid hyperthermia. The latter technique that has been developed as a cancer treatment for several decades comprises the injection of magnetic nanoparticles into tumors and their subsequent heating in an alternating magnetic field. Depending on the applied temperature and the duration of heating this treatment either results in direct tumor cell killing or makes the cells more susceptible to concomitant radio-or chemotherapy. Numerous groups are working in this field worldwide, but only one approach has been tested in clinical trials so far. Here, we summarize the clinical data gained in these studies on magnetic fluid induced hyperthermia.

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Targeting liver tumors with hyperthermia: Ferromagnetic embolization in a rabbit liver tumor model

Cited by 105 publications

References 42 publications

Study of the intra-arterial distribution of Fe3O4 nanoparticles in a model of colorectal neoplasm induced in rat liver by MRI and spectrometry

Study of the intra-arterial distribution of Fe3O4 nanoparticles in a model of colorectal neoplasm induced in rat liver by MRI and spectrometry

Selective hyperthermia using magnetoliposomes to target cervical lymph node metastasis in a rabbit tongue tumor model

Clinical applications of magnetic nanoparticles for hyperthermia

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