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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.

Abstract
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.
AuthorsHisataka Kobayashi, Satomi Kawamoto, Marcelino Bernardo, Martin W Brechbiel, Michael V Knopp, Peter L Choyke
JournalJournal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 111 Issue 3 Pg. 343-51 (Apr 10 2006) ISSN: 0168-3659 [Print] Netherlands
PMID16490277 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)
Chemical References
  • Contrast Media
  • Dendrimers
  • PAMAM Starburst
  • Polyamines
  • Gadolinium
Topics
  • Animals
  • Contrast Media (chemistry)
  • Dendrimers
  • Female
  • Gadolinium (analysis)
  • Lymph Nodes (metabolism)
  • Lymphatic Metastasis
  • Magnetic Resonance Imaging
  • Mammary Neoplasms, Experimental (diagnosis, radiotherapy)
  • Mice
  • Models, Animal
  • Nanoparticles
  • Neutron Capture Therapy
  • Polyamines (chemistry)

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