Detection of magnetic nanoparticles for clinical interventions

In this thesis the possibilities of detection of magnetic nanoparticles for clinical interventions are investigated. Detection of these particles in, for example, the sentinel lymph node procedure, is a good alternative for the radionuclide based methods currently in use. The thesis shows that the magnetic method can be only successful if the magnetic properties of the human tissue and the particles are effectively discriminated. Because of the dominating diamagnetic response of the surrounding tissue volume, a tiny amount of magnetic nanoparticles deeply located in the body cannot be detected using only a simple sinusoid excitation field. For an experimental exploration of the ex vivo sentinel lymph node procedure in colorectal cancer using magnetic nanoparticles, a method has been developed using vibrating sample magnetometry, to quantify the amount of magnetic nanoparticles in small tissue samples. In a small group of ten patients the magnetic tracer is tested ex vivo in combination with blue dye, directly after resection of the tumor area. Based on the selection of the three nodes closest to the tumor, the magnetic nanoparticles are detected in at least one of the three nodes in nine patients. This demonstrates the feasibility of the magnetic tracer for ex vivo sentinel lymph node mapping. In four patients occult metastases were found by the sentinel lymph node procedure. For clinical detection of magnetic nanoparticles during interventions, the patented DiffMag concept has been developed, which specifically exploits the nonlinear magnetic properties of the nanoparticles and eliminates the diamagnetic contribution of tissue. A sinusoidal excitation field (B ~2 mT, f ~ 5 kHz) is combined with a sequence of offsets that alternates between zero and a constant value, to modulate the nonlinear response of the particles, while the diamagnetic response remains constant. The modulation in the measured signal is the DiffMag response, which is uniquely attributed to the particles and depends on the particle core size distribution. In lymph node tissue this response is reduced by environmental effects on Brownian relaxation. The effect of environmental factors is confirmed using samples with different viscosities, particle volume change by biomolecule adhesion and particle uptake in macrophages.