Magnetic procedure for sentinel lymph node detection and evaluation of metastases: design and rationale of the Lowmag trial

Abstract

Abstract Background Primary tumour biology and axillary lymph node status are key prognostic factors in breast cancer treatment. The LowMag trial introduced a magnetic sentinel lymph node biopsy procedure using a superparamagnetic iron oxide (SPIO) tracer and a handheld magnetometer as a radiation-free alternative for axillary staging. The trial aimed to assess a low-dose magnetic tracer for non-invasive preoperative evaluation of lymph node metastases and intraoperative sentinel lymph node detection. Methods Patients with confirmed invasive breast cancer or ductal carcinoma in situ, eligible for sentinel lymph node biopsy, were included in the LowMag trial. The sentinel lymph nodes were detected perioperatively using Sentimag® and inked to maintain spatial orientation between MRI and histopathology. The amount of iron was estimated using two magnetic devices: SPaQ and Sentimag®. Additional ex vivo MRI was performed with a low-field MRI system. After being buffered in formalin, the sentinel lymph nodes were sectioned perpendicular to the MRI planes, consecutively sliced at 2 μm intervals, and stained with H&E, Perls Prussian blue, CK8/18, and CD68. Results In an interim assessment of 20 sentinel lymph nodes, two contained metastases. The analysis revealed good concordance in uptake between the magnetic and radioactive tracers, with a median iron content of 19.21 µg. In healthy sentinel lymph nodes, iron particles were found in both the subcapsular space and sinusoids, with macrophages nearby. Healthy regions within metastatic lymph nodes showed similar behaviour to healthy nodes. In metastatic sites, iron pigment presence was reduced, especially in areas occupied by tumour cells. A healthy lymph node with low iron content displayed a large central fatty region without iron uptake but confirmed iron in sinusoidal macrophages. The metastatic lymph node had subcapsular and parenchymal tumour cells in the central region, with limited infiltration into nearby adipose tissue and no local iron enhancement. However, iron deposits were detected within the sinusoids. Discussion The MRI images effectively distinguish between fat, nodal tissue, and the SPIO tracer, either through signal intensity or texture. This demonstrates the potential for sentinel lymph node imaging using a low-field MRI system.