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.
Kobayashi
Hisataka
H
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
Kawamoto
Satomi
S
Bernardo
Marcelino
M
Brechbiel
Martin W
MW
Knopp
Michael V
MV
Choyke
Peter L
PL
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