Sentinel node imaging is commonly performed prior to surgery for
breast cancer and
melanoma. While current methods are based on radio-lymphoscintigraphy, MR lymphangiography (MRL) offers the benefits of better spatial resolution without ionizing radiation. However, the optimal nanoparticle for imaging the sentinel nodes remains unclear.
Gadolinium-labeled (Gd)
contrast agents ranging in diameter from <1 to 12 nm were evaluated to determine which size provides the most rapid and most concentrated delivery of
contrast agent to the lymph nodes in a mouse model of
lymphatic metastases. Specifically, PAMAM-G2, -G4, -G6 and -G8, and DAB-G5 Gd-
dendrimer agents, as well as
Gadomer-17 and
Gd-DTPA, were compared. Among these agents, the G6 Gd
dendrimer depicted the lymphatics and lymph nodes with the highest peak concentrations and this occurred 24-36 min post-injection (p<0.01; all except G8). Based on ex vivo concentration phantoms, high accumulations of Gd(III)
ions occurred within lymph nodes (1.7-4.4 mM Gd/270-680 ppm Gd) with high target to background ratios (>100). These concentrations are sufficient to contemplate the use of Gd-
neutron capture therapy of regional lymph nodes. Thus, when injected interstitially, the PAMAM-G6 Gd
dendrimer not only provides excellent opacification of sentinel lymph nodes, but also provides the potential for targeted
therapy of sentinel lymph nodes.