Tumor cells and tumors can be effectively killed by thermal stress, also called hyperthermia [1]. This promising approach has already been tested in clinical studies. There, a lack of the ability to homogeneously deposit cytotoxic temperatures in the tumor area to reach all tumor cells led to unsatisfactory results. Hyperthermia can be optimized by using magnetic fluids, like for example iron oxide magnetic nanoparticles (MNP), which are deposited directly in the tumor, and which produce heat when placed inside of an alternating magnetic field (AMF)....

We used athymic nude mice bearing subcutaneously implanted breast cancer xenografts derived from the cell line MDA-MB-231. MNP were produced by Liquids Research Limited (Bangor, UK) by means of the co-precipitation technique [2] and were coated with dimercapotsuccinymid acid. Intratumoral injection of MNP was performed by slow bolus injection of 0.25 mg Fe / 100 mm3 tumor. Mice were then imaged using a microCT Scanner (TomoScope Synergy Twin, CT-Imaging GmbH, Erlangen, Germany) using a low radiation dose protocol (29 s, 65 kV) under isoflurane anesthesia....

MNP had a core diameter of 12 nm, a hydrodynamic diameter of 77 nm and a specific absorption in rate in water of 900 ± 22 W/g Fe. After intratumoral application, nanoparticles became clearly visible in the microCT (Figure 1) and the extent of heterogeneity in distribution could be analyzed. Proximity to non-tumor tissue and the spine could also be measured. During in vivo magnetic heating tumor surface temperature was controlled to be between 42 and 50°C. Tumor regression as observed macroscopically correlated clearly with...

By monitoring MNP distribution after intratumoral injection, planning and outcome of magnetic hyperthermia therapy can be improved. Known regions of MNP under-supply can be reached by increasing AMF power. Safety of the treatment can be improved by avoiding high temperatures in regions where MNP are close to non-tumor structures.

The described work was carried out within the project “Multifunctional Nanoparticles for the Selective Detection and Treatment of Cancer”, which is funded by the European Seventh Framework Program (FP7/2007-2013) under grant agreement no. 262943. We acknowledge Liquids Research Limited, Deiniol Road, Bangor, Gwynedd, United Kingdom for providing the magnetic material. Contact: [email protected] [email protected]

[1] Hilger I, Rapp A, Greulich K-O, Kaiser WA. Assessment of DNA damage in target tumor cells after thermoablation in mice. Radiology. 2005 Nov;237:500–6. [2] Reimers, G.W. and S.E. Khalafalla, US Bureau of Mines, Tech. Prog. Rep. 59, 1972.