Magnetic particle imaging enables nonradioactive quantitative sentinel lymph node identification: feasibility proof in murine models

Olivia C Sehl; Kelvin Guo; Abdul Rahman Mohtasebzadeh; Petrina Kim; Benjamin Fellows; Marcela Weyhmiller; Patrick W Goodwill; Max Wintermark; Stephen Y Lai; Paula J Foster; Joan M Greve

doi:10.1093/radadv/umae024

Magnetic particle imaging enables nonradioactive quantitative sentinel lymph node identification: feasibility proof in murine models

Radiol Adv. 2024 Oct 25;1(3):umae024. doi: 10.1093/radadv/umae024. eCollection 2024 Sep.

Authors

Affiliations

¹ Magnetic Insight Inc., Alameda, CA 94502, United States.
² Departent of Medical Biophysics, University of Western Ontario, Robarts Research Institute, London, ON N6A 3K7, Canada.
³ Department of Neuroradiology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States.
⁴ Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States.

Abstract

Background: Sentinel lymph node biopsy (SLNB) is an important cancer diagnostic staging procedure. Conventional SLNB procedures with ^99mTc radiotracers and scintigraphy are constrained by tracer half-life and, in some cases, insufficient image resolution. Here, we explore an alternative magnetic (nonradioactive) image-guided SLNB procedure.

Purpose: To demonstrate that magnetic particle imaging (MPI) lymphography can sensitively, specifically, and quantitatively identify and map sentinel lymph modes (SLNs) in murine models in multiple regional lymphatic basins.

Materials and methods: Iron oxide nanoparticles were administered intradermally to healthy C57BL/6 mice (male, 12-week-old, n = 5). The nanoparticles (0.675 mg Fe/kg) were injected into the tongue, forepaw, base of tail, or hind footpad, then detected by 3-dimensional MPI at multiple timepoints between 1 hour and 4 to 6 days. In this mouse model, the SLN is represented by the first lymph node draining from the injection site. SLNs were extracted to verify the MPI signal ex vivo and processed using Perl's Prussian iron staining. Paired t-test was conducted to compare MPI signal from SLNs in vivo vs. ex vivo and considered significant if P < .05.

Results: MPI lymphography identified SLNs in multiple lymphatic pathways, including the cervical SLN draining the tongue, axillary SLN draining the forepaw, inguinal SLN draining the tail, and popliteal SLN draining the footpad. MPI signal in lymph nodes was present after 1 hour and stable for the duration of the study (4-6 days). Perl's Prussian iron staining was identified in the subcapsular space of excised SLNs.

Conclusion: Our data support the use of MPI lymphography to specifically detect SLN(s) using a magnetic tracer for a minimum of 4 to 6 days, thereby providing information required to plan the SLN approach in cancer surgery. As clinical-scale MPI is developed, translation will benefit from a history of using iron-oxide nanoparticles in human imaging and recent regulatory-approvals for use in SLNB.

Keywords: iron oxide nanoparticles; lymphography; magnetic particle imaging; pharmacokinetics; quantitative; sentinel lymph node; surgical planning; vivotrax.