Info
Background:
Sentinel lymph node biopsy (SLNB) is used to stage solid tumors, but radiotracer-based workflows depend on tight clinical scheduling because of radionuclide decay and are limited by the shine-through artifact, in which residual activity at the injection site masks adjacent sentinel lymph nodes (SLNs) [1]. Magnetic tracers such as ferucarbotran avoid radioactivity but image poorly before surgery, as they were optimized for MRI rather than magnetic particle imaging (MPI). MPI detects superparamagnetic iron oxide nanoparticles (SPIOs) directly, with high sensitivity, positive contrast, quantitative signal, and no ionizing radiation. High-resolution single-core SPIOs have recently been reported for MPI, yet no biocompatible aqueous formulation has retained their magnetic performance in vivo.
Hypothesis/Objective:
This study describes a biocompatible high-resolution MPI tracer obtained by transferring single-core SPIOs into water through a single-step albumin coating,and characterizes its behavior in lymph node imaging and macrophage cell tracking.
Methods:
Albumin-coated SPIOs (Alb-SPIOs) were prepared by oil-in-water emulsification of oleic acid-coated SPIO cores with bovine (BSA) or human serum albumin (HSA). Crosslinked variants were produced using glutaraldehyde (GTA-xAlb-SPIO) or glucose (Glc-xAlb-SPIO) to test how surface chemistry affects lymphatic transport. Hydrodynamic size, zeta potential, and morphology were measured by dynamic light scattering, electrophoretic mobility, and transmission electron microscopy. Sensitivity and spatial resolution were determined from phantoms on a MOMENTUM scanner (5.7 T/m gradient). For lymphography, Alb-SPIOs or ferucarbotran (14 µg Fe) were injected intradermally into the hind footpad of BALB/c mice (n = 3 per tracer, 5 tracers, 15 mice total). Whole-body MPI was acquired serially over 14 days, and percent injected dose (%ID) was measured at the draining popliteal lymph node (pLN) and the injection site. Iron in excised nodes was verified by Perls’ Prussian blue staining.
Results:
Albumin coating retained the magnetic performance of the single-core cores after transfer into water. The detection limit of BSA-SPIO was 44 ng Fe, roughly four-fold below that of ferucarbotran (175 ng Fe), at a spatial resolution under 0.8 mm. Neither macrophages nor mesenchymal stem cells showed appreciable toxicity after labeling, and macrophages took up Alb-SPIOs while remaining viable. After intradermal injection, Alb-SPIOs reached the draining lymph nodes within 30 minutes and stayed detectable for at least 14 days. HSA-SPIO gave the highest pLN uptake at 14.2 ± 1.9 %ID and cleared efficiently from the injection site, yielding a pLN-to-injection-site signal ratio of 1.52; ferucarbotran reached only 2.0 ± 1.1 %ID with a ratio of 0.077, a roughly 20-fold difference in nodal contrast. Crosslinked formulations traveled further along the lymphatic chain to higher-echelon nodes, in line with corona-dependent differences in biodistribution. pLN signal remained for at least 14 days and was confirmed histologically.
Conclusion:
A biocompatible high-resolution MPI tracer is reported that keeps the performance of optimized single-core SPIOs after aqueous transfer. Together with its higher sensitivity, the lymphatic kinetics of Alb-SPIOs can be tuned through surface chemistry, giving strong nodal accumulation alongside injection-site clearance and addressing the shine-through that constrains SLNB. For context, SPIOs in human studies deposit under 1% of the injected iron in lymph nodes (about 0.1 %ID for Resovist or Magtrace), reflecting inefficient lymphatic delivery by current magnetic tracers [2-5]. The same tracer supports sentinel lymph node mapping and quantitative cell tracking by MPI.
Author
Steven Conolly, PhD
UC Berkeley