Ultra-Low Dose Superparamagnetic Iron Oxide Nanoparticles for Sentinel Lymph Node Detection in Breast Cancer: A Literature Review.

Superparamagnetic iron oxide (SPIO) nanoparticles are effective non-radioactive alternatives for sentinel lymph node biopsy in breast cancer. However, standard doses (1-2 mL) cause skin staining in 30.8% of patients and magnetic resonance imaging (MRI) artifacts in 50% to 67% of cases. Ultra-low dose (0.1 mL) protocols have been developed to address these limitations. Systematic literature search of PubMed, Embase, and Cochrane databases through December 2025 identified studies evaluating ultra-low dose SPIO, focusing on detection efficacy, adverse effects, and injection techniques. Ultra-low dose SPIO achieved 100% detection rate in feasibility studies with injection 1 to 7 days preoperatively (median 4 days representing a 90% reduction compared with standard protocols. Dose-response data show skin staining reduction from 26.4% to 17% with modest dose decrease (1.5 to 1.0 mL), suggesting greater benefit with ultra-low dosing. MRI artifacts appear significantly reduced, particularly with peritumoral injection ensuring tracer excision during lumpectomy. Ultra-low dose SPIO maintains detection efficacy while substantially reducing adverse effects. This approach benefits high-risk patients requiring breast MRI and younger patients with cosmetic concerns. While randomized trials are needed, current evidence supports clinical implementation with appropriate patient selection.