Hybrid ⁹⁹mTc-magnetite tracer for dual modality sentinel lymph node mapping

Abstract

Accuracy of sentinel lymph node identification using radioactive tracers in non-superficial cancers can be limited by radiation shine through and low spatial resolution of detection systems such as intraoperative gamma probes. By utilising a dual radioactive/magnetic tracer, sensitive lymphoscintigraphy can be paired with high spatial resolution intraoperative magnetometer probes to improve the accuracy of sentinel node detection in cancers with complex multidirectional lymphatic drainage. Dextran-coated magnetite nanoparticles (33 nm mean hydrodynamic diameter) were labelled with 99mTc and applied as a lymphotropic tracer in small and large animal models. The dual tracer could be radiolabelled with 98 ± 2% efficiency after 10 min of incubation at room temperature. Biodistribution studies of the tracer were conducted in normal rats (subdermal and intravenous tail delivery, n = 3) and swine (subdermal hind limb delivery, n = 5). In rats the dual tracer migrated through four tiers of lymph node, 20 min after subdermal injection. Results from intravenous biodistribution test for radiocolloids demonstrated no aggregation in vivo, however indicated the presence of some lower-molecular weight radioactive impurities (99mTc-dextran). In swine, the dual tracer could be effectively used to map lymphatic drainage from hind hoof to popliteal and inguinal basins using intraoperative gamma and magnetometer probes. Of the eight primary nodes excised, eight were positively identified by gamma probe and seven by magnetometer probe. The high-purity dual tracer shows early promise for sentinel node identification in complex lymphatic environments by combining sensitive preoperative lymphoscintigraphy with a high-resolution intraoperative magnetometer probe.