What advantages does thermotherapy with nanoparticles have?

The cell-damaging effect of hyperthermia has been used therapeutically for a long time. Common hyperthermia procedures utilize various energy sources to generate a temperature increase within the tissue: externally radiated electromagnetic waves (such as radiofrequency or microwave hyperthermia), ultrasound (external or interstitial), current flow between two or more electrodes, electrical or magnetic fields between implanted antennas, electrically or magnetically activated thermoseeds or tubes fed with warm water. The greatest problem with the hyperthermia procedures used today is achieving homogeneous heat distribution in the treated tissues. If this is not achieved, results may include an undersupply in tumor areas or organ damage due to excessively high temperatures in other regions.

Nano-Cancer^® therapy is a special form of local deep thermotherapy. It has the advantage that for the first time, heat deposition specifically targets the tumor cells, thereby largely meeting the need for maximum deposition of the heat dosage in the target volume while sparing the surrounding healthy tissues as much as possible. In addition, for the first time thermotherapy with magnetic nanoparticles allows physicians free selection of the target temperature after one-time application of the nanoparticles, which - depending on the clinical indication - they can utilize as hyperthermia for localized boosting of conventional radiation or chemotherapy (up to 45°C / 113°F), or with a corresponding indication, also by itself as thermoablation, with high temperatures up to 70°C / 158°F. This even functions when utilized subsequently in one and the same patient.

How does Nano-Cancer^® therapy work in detail?

The treatment method is based on a defined energy transmission to biocompatible superparamagnetic nanoparticles in an alternating magnetic field. The resulting high heat production is determined by the particle type, the frequency of the radiated alternating magnetic field and the magnetic field intensity. Furthermore, the nanotechnological design of the covering enables differentiated intracellular absorption, preferably into rapidly proliferating cells such as tumor cells. Furthermore, thermotherapy with magnetic nanoparticles offers other fundamental advantages:

• The magnetic fluid can be meted out in the target volume in the amounts as small as necessary and therefore be dispensed almost continuously.
• Due to the known energy absorption per nanoparticle, the energy transmission can be calculated from the density distribution which is measured in the CT. This enables the three-dimensional calculation and planning of the temperature distribution.
• The introduction of a defined total quantity into a target volume enables an ability to exercise control which is not provided in any other interstitial procedure.
• Through the intracellular absorption of the particles into the tumor cells, tumor cells in the surroundings of the macroscopic tumor - which are generally not covered by non-specific therapy, that is, therapy which is oriented solely along the contrast enhanced image - are also reached. Furthermore, the cancer cells are not able to eject the particles again.
• The collapse of tissue barriers with corresponding heating causes improved diffusability and therefore a spread of the magnetic fluid in the target volume. In the course of the external contact-free activation of the particles by means of the alternating magnetic field applicator, any desired number of treatments is possible without additional traumatization.
  

What attributes do nanoparticles possess?

The magnetic fluid consists of superparamagnetic nano-scaled iron oxide particles in an aqueous solution with an iron concentration of approximately 111 mg/mL. The nanoparticles consist of an iron oxide core with a diameter of approximately 15 nm and a coating of aminosilanes. This covering allows the colloidal dispersion of the particles in an aqueous solution. The core, which consists of magnetite, has intrinsic magnetic energy which is activated by the externally applied alternating magnetic field. Due to relaxation processes, the particles release heat into their surroundings.

How are the particles introduced into the tumor?

In principle, the instillation of the nanoparticles can be done with any commercially available cannula, since the viscosity of the magnetic fluid approximately corresponds to that of water. Three to ten milliliters are applied in three to twenty punctures. Precise positioning of the nanoparticles plays a decisive role in covering the target volume. A simulation program is used to calculate optimal quantities and sites for the instillation of nanoparticles, which are provided to the physician. Four different procedures for the instillation of defined quantities of magnetic fluid have been utilized thus far:

• Navigation or stereotaxy control for brain tumors: The instillation trajectories are entered into a navigation or stereotaxy system. Analogous to the removal of biopsy samples, the distal point in the tumor is located, and the fluid is instilled while the cannula is withdrawn.
• TRUS control in prostate tumors: Using a transrectal ultrasound, the positions for instillation into the prostate are determined analogously to radioactive seed implantation. The magnetic fluid is likewise injected as the cannula is withdrawn to a previously determined length.
• CT control: The injection cannula is guided to previously determined positions under direct CT control. The entry point, direction of insertion and depth of the puncture are determined in advance.
• Intraoperatively in an R1 situation: If it is found during surgery that specific tumor areas cannot be removed, the magnetic fluid can be infiltrated directly into the exposed R1 region. The required amount of nanoparticles is estimated and then distributed by the physician as evenly as possible.
  

In all application modes, the positioning of the nanoparticles is determined by a subsequent CT and the heat distribution is calculated in a post-instillation analysis (PIA).

How is treatment in the magnetic field applicator carried out?

Nano-Cancer^® therapy is carried out in a magnetic field applicator (MFH®-300F) which was developed specifically for this form of therapy. The unit has an adjustable treatment gap with a width which extends from 21 to 33 centimeters. The spool current of the 100 kHz oscillating cycle is continuously adjustable from 100 to 500 A. The magnetic alternating field can be adjusted depending on the gap distance, the spool current and the vertical distance from the gap centre, from approximately 2-18 kA/m. Within the treatment gap, the desired overheating region can be positioned in a circular area with a diameter of approximately 20 cm. Neither immobilization nor anesthesia of the patient is required to perform thermotherapy.

Due to its construction, the alternating magnetic field applicator is universally usable for tumors in all body regions. Temperature measurements during therapy are made in a minimally invasive manner with a fluoroptical measuring system and corresponding display and documentation software. The entire duration of treatment takes approximately two hours and in addition to the 60-minute therapy period, includes the time for warming up the target area as well as periods for preparation and positioning of the patient.