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Anjali A Roeth,1,* Ioana Slabu,2,* Martin Baumann,2 Patrick H Alizai,1 Maximilian Schmeding,1 Gernot Guentherodt,3 Thomas Schmitz-Rode,2 Ulf P Neumann1 1Department of General, Visceral and Transplant Surgery, University Hospital RWTH Aachen, 2Institute of Applied Medical Engineering, Helmholtz-Institute Aachen, RWTH Aachen, Aachen, 3Institute of Physics A, RWTH Aachen University, Aachen, Germany *These authors contributed equally to this work Abstract: Superparamagnetic iron oxide nanoparticles (SPION) may be used for local tumor treatment by coupling them to a drug and accumulating them locally with magnetic field traps, that is, a combination of permanent magnets and coils. Thereafter, an alternating magnetic field generates heat which may be used to release the thermosensitively bound drug and for hyperthermia. Until today, only superficial tumors can be treated with this method. Our aim was to transfer this method into an endoscopic setting to also reach the majority of tumors located inside the body. To find the ideal endoscopic magnetic field trap, which accumulates the most SPION, we first developed a biophysical model considering anatomical as well as physical conditions. Entities of choice were esophageal and prostate cancer. The magnetic susceptibilities of different porcine and rat tissues were measured with a superconducting quantum interference device. All tissues showed diamagnetic behavior. The evaluation of clinical data (computed tomography scan, endosonography, surgical reports, pathological evaluation) of patients gave insight into the topographical relationship between the tumor and its surroundings. Both were used to establish the biophysical model of the tumors and their surroundings, closely mirroring the clinical situation, in which we could virtually design, place and evaluate different electromagnetic coil configurations to find optimized magnetic field traps for each tumor entity. By simulation, we could show that the efficiency of the magnetic field traps can be enhanced by 38-fold for prostate and 8-fold for esophageal cancer. Therefore, our approach of endoscopic targeting is an improvement of the magnetic drug-targeting setups for SPION tumor therapy as it holds the possibility of reaching tumors inside the body in a minimal-invasive way. Future animal experiments must prove these findings in vivo. Keywords: drug targeting, simulation, SPION, prostate cancer, esophageal cancer |
