Not sure how far this will proceed, but it has been in R&D for a...

Not sure how far this will proceed, but it has been in R&D for a good number of years, so hopefully they have something. Could be another 5 years plus before there is any commercial benefit.
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Press release - source -  NewsRx LLC
09/17/2014 | 05:24pm US/Eastern

By a News Reporter-Staff News Editor at Biotech Week -- According to news reporting originating from Washington, D.C., by NewsRx journalists, a patent application by the inventors Jones, Stephen Keith (North Curl Curl, AU); Rutherford, Katrina Francis (Dundas Valley, AU); Ruys, Andrew John (Pymble, AU); Gray, Bruce Nathaniel (Claremont, AU), filed on May 15, 2014, was made available online on September 11, 2014 (see also Sirtex Medical Limited).

The assignee for this patent application is Sirtex Medical Limited.

Reporters obtained the following quote from the background information supplied by the inventors: "The following discussion provides the background to one aspect of the potential uses of the present invention. This discussion should not be read as a limitation on the possible uses to which the present invention may be put. In this respect it should be appreciated that the microparticle compositions of the invention may be used to heat any object provided the microparticles can be arranged in a manner that facilitates heating of the object via the heating effects of the microparticles when placed in a suitable magnetic field.

"Diseases of the human body such as malignant tumours are generally treated by excision, chemotherapy, radiotherapy or a combination of these approaches. Each of these is subject to limitations which effects clinical utility. Excision may not be appropriate where the disease presents as a diffuse mass or is in a surgically inoperable locality. Chemotherapeutic agents are generally non-specific, thus resulting in the death of normal and diseased cells. As with chemotherapy, radiotherapy is also non-specific and results in the death of normal tissues exposed to ionizing radiation. Furthermore, some diseases such as tumours may be relatively resistant to ionizing radiation. This is a particular problem with the core of a tumour mass.

"As an alternative, hyperthermia has been proposed as a treatment of diseased tissue. There is evidence to suggest that hyperthermia is effective in treating diseases, including cancerous growths. The therapeutic benefit of hyperthermia therapy is mediated through two principal mechanisms. Firstly, hyperthermia therapy has a direct tumouricidal effect on tissue by raising temperatures to greater than 42.degree. C. resulting in irreversible damage to cancer cells. Secondly, hyperthermia is known to sensitise cancer cells to the effects of radiation therapy and to certain chemotherapeutic drugs. The lack of any cumulative toxicity associated with hyperthermia therapy, in contrast to radiotherapy or chemotherapy, is further justification for seeking to develop improved systems for hyperthermia therapy.

"Several techniques are presently available for inducing clinical hyperthermia either regionally, in selected local regions of specific organs or over the whole body. These techniques include the use of plain wave electromagnetic radiation, such as microwave heating and radiofrequency waves, and ultrasound.
"The above techniques have their limitations, including poor tissue penetration and a rapid decline of energy with increasing depth; perturbations induced by tissue interfaces such as air and bone; variation in the heating effect or focusing for deep organ heating.

"In addition, there are other problems associated with the currently available methods for inducing clinical hyperthermia in human patients. Normal body tissues and organs are heat sensitive and at temperatures of greater than 42.degree. C. many tissues will undergo irreversible damage. In addition, the methods currently available for delivering clinical hyperthermia are non-specific, that is, heat normal tissues as well as tumour cells.
"For hyperthermia treatment to be effective, there are two basic requirements. Firstly, there is a need to localise the treatment to the target site and secondly, there is a need to maximise heating within the target site while maintaining hyperthermia therapy within safe operating limits for the patient.

"One proposed solution when using hyperthermia therapy involves the use of small magnetic particles that can be heated by applying a high frequency alternating magnetic field. The particles may then be delivered to the target site in a variety of ways, e.g. direct injection, antibody targeting or intravascular infusion. An alternating magnetic field is then applied and heat from the particles causes the tumour temperature to rise above the therapeutic threshold of 42.degree. C. The magnetic field conditions must be such as to cause no interaction with tissue, only with the magnetic particles. In this way, only tissue containing a concentration of the magnetic particles will be heated, irrespective of its location in the body.

"In general, the small magnetic particles are iron oxide particles covered with a polymer coating, such as dextran. Although such complexes have been used in vitro, any in vivo use has been limited by the method of injection used and also as a result of the breakdown of the dextran coating within the body. No clinical studies in human patients have yet been attempted using these particles.

"Numerous publications describe various potential schemes for a treatment of cancer by induced hyperthermia using the heat generated by small magnetic particles when exposed to an AC magnetic field. These publications are almost entirely based on experimental results showing the production of heat from magnetic particles in a laboratory scenario. Fewer publications show a system working in an animal model and no publications to date present clinical data from actual human patients.

"The reasons for this lack of clinical application, despite the obvious potential of the idea, are problems associated with safety, delivery of a therapeutically effective amount of magnetic material to the target site and achieving adequate heating of the target site only. To date, all previously reported systems fail to meet at least one of these requirements.
"The major issue with safety is the strength and frequency of the applied magnetic field to be used in heating the magnetic particles. There is currently no way to reliably produce a long narrow beam of magnetic field that only exposes a small area of the patient to the AC field. Hence, systems must be designed assuming the patients' whole body will be exposed to the AC field. This places serious constraints on the amplitude and frequency of the field that can be used since there are potentially hazardous physiological responses to AC fields once the frequency and/or amplitude becomes high enough. These responses include involuntary neuromuscular stimulation and magnetically induced eddy current heating of non-target tissue. In the extreme case, the AC magnetic fields may even cause deadly cardiac arrhythmias.

"The heating quality of the complexes including magnetic particles is termed the volumetric absorption rate (VAR) and is defined as the amount of heat released by a unit volume of the complex per unit time during exposure to a magnetic field of a defined frequency and field strength.

"To be therapeutically effective, the VAR level should be maintained after the complex has been administered to the patient and have come in contact with biological fluids. For example, the dextran coated particles in the prior art may loose their dextran coatings due to lysosomal enzymatic dextran digestion when used for intracellular MFH (magnetic fluid hyperthermia). This causes particle aggregation and consequent degradation of heating and as such, dextran coated magnetite nanoparticles are not suitable for intracellular MFH.

"Many schemes are aimed at ensuring the localised deposition of heat to the cancer tissue, such as direct injection and antibody targeting. Although direct injection may be used to administer high quantities of the magnetic material to a tumour, the technique does have substantial disadvantages, including: (1) tumours must be accurately located and rendered accessible for injection to take place, (2) the physical penetration of tumours can lead to further spread of the cancer, and (3) injected material may not stay in the injected region.

"Antibody targeting has not been shown to work effectively, to date. The very small particles of the type required for antibody targeting are also effectively removed from circulation in the blood stream via the reticuloendothelial system. Thus, only short circulation half lives are possible and, hence, limited exposure of the antibody bearing particles to the target cancer cells. At the presently achievable levels of cellular uptake of antibody targeted particles, VAR values far in excess of those presently available would be required to achieve adequate tumour heating even for larger tumours.
"Despite the clear advantages of complexes including magnetic particles, there has been no successful utilisation of this methodology in the treatment of human disease to date. This is most likely because of the difficulties faced when scaling up experimental systems to a size suitable for human application. Primary amongst these is the fact that magnetic field conditions (strength and frequency) which might appear safe when used in experiments with small animals, will most likely be unsuitable for use in human patients. However, reduction in the field and or frequency of the AC magnetic field to a level that is safe in human patients invariably leads to a reduction of the VAR of the magnetic material used to heat the tumours to the point where the system becomes useless as a treatment for human patients.
"Therefore, there exists a need to develop microparticle composition(s) for heating an object or a target site, when the object or target site is exposed to appropriate magnetic field conditions."

In addition to obtaining background information on this patent application, NewsRx editors also obtained the inventors' summary information for this patent application: "The subject invention relates to microparticle composition(s) capable of heating an object or inducing hyperthermia in a target site when the object or target site is exposed to an alternating magnetic field. The microparticle composition(s) of the invention generate substantial quantities of heat when exposed to a high frequency alternating magnetic field. In one example, the invention relates to microparticle composition(s) for treating diseased tissue by targeted hyperthermia.

"According to a first aspect of the invention, there is provided a microparticle composition(s) comprising: nanomagnetic particles and a matrix, wherein said microparticle composition(s) have at least one of the following properties: (a) a VAR of at least about 1 Watts/cm.sup.3 subject to appropriate field conditions; (b) a density of about 2.7 or less; or © a size of about 100 nm to about 200 microns.

"According to a second aspect of the invention, there is provided a preparation of microparticle composition(s) comprising nanomagnetic particles and a matrix, wherein less than approximately 40% of the microparticle composition(s) is nanomagnetic particles and having at least one of the following properties: (a) a VAR of at least about 10 Watts/cm.sup.3 subject to appropriate field conditions; (b) a density of about 2.7 or less; or © a size of about 100 nm to 200 microns.

"According to a third aspect of the invention there is provided a microparticle composition(s), as herein described, which is adapted for use in a patient and which is capable of heating tissue from that patient when exposed to an alternating magnetic field.

"According to a fourth aspect of the invention there is provided a method for heating a target site in a patient including the steps of: (i) administering a microparticle composition(s) as herein described to a target site in said patient; and (ii) exposing the target site to an AC magnetic field of a clinically acceptable frequency and strength, which is capable of inducing heating of the target site.

"According to a fifth aspect, the invention resides in the use of a microparticle composition, as herein described, for the preparation of a medicament or therapeutic for the treatment of diseased tissue."