Delivery of gadolinium-labeled nanoparticles to the sentinel lymph node: comparison of the sentinel node visualization and estimations of intra-nodal gadolinium concentration by the magnetic resonance imaging.
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.
Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10, Room 1B40, MSC1088, 10 Center Drive, Bethesda, MD 20892-1088, USA. Kobayash@mail.nih.gov
Hisataka
H
Kobayashi
Satomi
S
Kawamoto
Marcelino
M
Bernardo
Martin W
MW
Brechbiel
Michael V
MV
Knopp
Peter L
PL
Choyke
D000818:Animals; D003287:Contrast Media / Q000737:chemistry; D050091:Dendrimers; D005260:Female; D005682:Gadolinium / Q000032:analysis; D008198:Lymph Nodes / Q000378:metabolism; D008207:Lymphatic Metastasis; D008279:Magnetic Resonance Imaging; D008325:Mammary Neoplasms, Experimental / Q000175:diagnosis* / Q000532:radiotherapy; D051379:Mice; D023421:Models, Animal; D053758:Nanoparticles; D017247:Neutron Capture Therapy; D011073:Polyamines / Q000737:chemistry
D003287:Contrast Media; D050091:Dendrimers; C104700:PAMAM Starburst; D011073:Polyamines; D005682:Gadolinium