Magnetic nanoparticles for sentinel lymph node imaging and biopsy in breast cancer

Student thesis: Doctoral ThesisDoctor of Philosophy


Background Axillary nodal status is the single most important prognostic factor in breast cancer diagnosis. If cancerous cells are present, the sentinel lymph node (SLN) is the axillary lymph node that is most likely to contain metastatic disease. In early stage breast cancer, the SLN is localised (then surgically removed for pathological analysis) using a radioisotope and/or a blue dye injected into the breast Super-paramagnetic iron oxide (SPIO) nanoparticles are novel agents that, when injected, could potentially both localise and characterise the SLN using MRI such that surgical SLN biopsy is no longer required. Aims To evaluate axillary SLN localisation after SPIO injection with, pre-operatively, axillary MRI and, intra-operatively, with a hand held magnetometer and to characterise SLN SPIO uptake using ex-vivo MRI. Methods From November 2009 - March 2011, 51 patients with early stage breast cancer underwent SLN biopsy following a subcutaneous injection of SPIO in addition to the standard injection of radioisotope (Tc99M) and blue dye. SPIO injection technique was refined during the trial with an initial dose of 2mls and then 4mls in 8 and then 43 women respectively. Pre-operative axillary in vivo MRI (1.5T) was carried out on 14 women and ex vivo high resolution MRI (9.4T) on 36 nodes. During surgery, an SLN was defined as either "hot", "blue", "palpable" or "SPIO detected". Axillary clearance was carried out for SLN-positive disease. Results In total, 11 of the 51 patients had positive SLNs.
On pre-operative axillary MRI, SPIO uptake was noted in at least one node in all 14 patients. A total of 35 nodes were identified. Uptake of SPIO in the SLN was seen at a minimum of 12mins post injection. Involved SLNs were not differentiated from normal SLNs following morphological characterisation or based on loss of T2 signal within the individual SLN. At SLN biopsy, 134 hot, blue, palpable or SPIO-containing nodes were identified in 51 patients. The magnometer identified 92 SPIO-containing nodes in 51 (84%) patients. One node in one patient was not identified using the combined technique but was found to contain SPIO. Of the 16 hot, blue or palpable involved nodes in 11 patients, 9 contained SPIO. In summary, the SPIO SLN localisation rate and FNR in patients was 84% and 16% respectively. Ex vivo SLN MRI demonstrated SPIO uptake in all 35 SLNs preferential to the sinuses and sub-capsular spaces. Of the 3 involved nodes, areas of metastasis did not take up SPIO, whereas in normal areas of the node, SPIO was positively identified. Conclusion In our study, subcutaneous SPIO, a novel SLN-localising agent, was taken up by axillary nodes and identified on pre-operative axillary MRI. Node positive SLNs were identified on ex vivo MRI, but SPIO did not demonstrate sufficient accuracy at SLN localisation for routine clinical use.
Date of Award2012
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorMichael Douek (Supervisor) & Arnie Purushotham (Supervisor)

Cite this