Invited Speaker

Nanotechnology in cancer
Manfred Georg Krukemeyer, W. Wagner

Introduction
Systemic chemotherapy is invariably associated with side effects, due to the fact that cytostatic drugs have an effect on all proliferating cells in the body. In order to render chemotherapy more effective and to reduce side effects, various methods of drug targeting have been developed. Here the cytostatic drug is coupled to a carrier and thus transported on target to the tumour, where it becomes detached from the carrier and delivers its effect locally.

The experiments presented here for magnetic drug targeting were conducted with ferrofluids. Ferrofluids are aqueous colloidal solutions made of magnetisable nanoparticles, comprising a Fe3O4 core with a coating, in this case made of dextran, which the cytostatic agent is coupled with. A magnetic field enables these nanoparticles to be passed through the body targeted to the tumour.

Material and methods
66 WAG-Rij rats were used as the test animals A rhabdomyosarcoma was implanted in the animals 2 weeks before the start of the study. The animals were anaesthetized for the study and placed under a magnetic field with a magnetic field strength of 0.6 tesla. The biodistribution of mitoxantrone was first investigated with the aid of various times with and without application of magnets with the same dosage. A dosage of 1 mg of mitoxantrone per kg of body weight was administered to the animals in all the experiments.

In the study on humans - we also used 1 mg/kg body surface - we administered 19.2 mg/m2 of body surface of mitoxantrone-coupled iron oxide (Fe3O4) slowly by the intravenous route, for four days, in total 80 mg/m2 of body surface. A woman with a mammary carcinoma, and a man with lung cancer were likewise placed under a magnetic field with a field strength of 0.6 tesla. Further dosage reduction has been investigated with 30 and 50 mg/m2 of body surface.

Results
The animal studies showed a focusing effect of the magnetic field on the iron particles under in vivo conditions.

The case history showed a reversible granulocytopenia after administration with ferrofluids, but no gastritis, stomatitis or other side effects. A reduction in tumour volume by 45 % from before to after administration was detected by MRT, four weeks later reduction by 90 % was detected after eight months. The other clinical cases with lung cancer and sarcoma show also encouraging results.

Conclusion
This therapy method is a possible and sufficient option for incurable tumours with relatively few side effects.

Curriculum vitae
Manfred George Krukemeyer, born in Muenster, Germany on 07.05.1961, read medicine at the University of Vienna, trained to be a surgeon in Muenster, Germany, a member of the Department of Surgical Research, Medical School of the University of Muenster (Germany) since 2002. Since 2009 Department of Radio-Onocology, Paracelsus Hospital of Osnabrück (Germany).