TY - JOUR
T1 - Delivery of gadolinium-labeled nanoparticles to the sentinel lymph node
T2 - Comparison of the sentinel node visualization and estimations of intra-nodal gadolinium concentration by the magnetic resonance imaging
AU - Kobayashi, Hisataka
AU - Kawamoto, Satomi
AU - Bernardo, Marcelino
AU - Brechbiel, Martin W.
AU - Knopp, Michael V.
AU - Choyke, Peter L.
N1 - Funding Information:
This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. We extend our thanks to Yutaka Tagaya, for providing the PT-18-7 cells for the validation study.
PY - 2006/4/10
Y1 - 2006/4/10
N2 - 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.
AB - 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.
KW - Breast cancer
KW - Gadolinium neutron capture therapy
KW - MRI
KW - Nanoparticle
KW - Sentinel lymph node
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U2 - 10.1016/j.jconrel.2005.12.019
DO - 10.1016/j.jconrel.2005.12.019
M3 - Article
C2 - 16490277
AN - SCOPUS:33645215048
SN - 0168-3659
VL - 111
SP - 343
EP - 351
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 3
ER -