Abstract

In this project we have developed dendrimer based nanoparticles which are labeled with optical, radionuclide and/or MRI contrast agents for use in sentinel node imaging in animal models of metastatic disease and eventually in humans. The purpose of this research is two fold. First, is to develop a better imaging agent for sentinel node imaging, one that combines two imaging modalities rather than the current method that requires two separate injections. This will lead to reduced morbidity of sentinel node resections and improve their reliability. An additional purpose is to investigate the mechanisms by which the lymphatics act as conduits for metastatic disease and how this process could be monitored and interfered with. We intend to develop the next generation of sentinel node imaging agents that are not merely passively targeted to the lymph node but actively targeted to metastases within the lymph node. Towards that end we have labeled the dendrimer nanoparticle with Fab Herceptin and will investigate other targeting ligands. We also hope to develop methods of evaluating lymphedema in human subjects to reduce suffering due to this disorder.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Division of Basic Sciences - NCI (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC010654-02
Application #
7338753
Study Section
(MIP)
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2006
Total Cost
Indirect Cost

  Institution

Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Tan, Esther; Weiss, Brendan M; Mena, Esther et al. (2011) Current and future imaging modalities for multiple myeloma and its precursor states. Leuk Lymphoma 52:1630-40
Padhani, Anwar R; Liu, Guoying; Koh, Dow Mu et al. (2009) Diffusion-weighted magnetic resonance imaging as a cancer biomarker: consensus and recommendations. Neoplasia 11:102-25
Kobayashi, Hisataka; Koyama, Yoshinori; Barrett, Tristan et al. (2007) Multimodal nanoprobes for radionuclide and five-color near-infrared optical lymphatic imaging. ACS Nano 1:258-64
Hama, Yukihiro; Koyama, Yoshinori; Urano, Yasuteru et al. (2007) Simultaneous two-color spectral fluorescence lymphangiography with near infrared quantum dots to map two lymphatic flows from the breast and the upper extremity. Breast Cancer Res Treat 103:23-8
Koyama, Yoshinori; Talanov, Vladimir S; Bernardo, Marcelino et al. (2007) A dendrimer-based nanosized contrast agent dual-labeled for magnetic resonance and optical fluorescence imaging to localize the sentinel lymph node in mice. J Magn Reson Imaging 25:866-71
Hama, Yukihiro; Koyama, Yoshinori; Urano, Yasuteru et al. (2007) Two-color lymphatic mapping using Ig-conjugated near infrared optical probes. J Invest Dermatol 127:2351-6
Xu, Heng; Regino, Celeste A S; Koyama, Yoshinori et al. (2007) Preparation and preliminary evaluation of a biotin-targeted, lectin-targeted dendrimer-based probe for dual-modality magnetic resonance and fluorescence imaging. Bioconjug Chem 18:1474-82
Hama, Yukihiro; Bernardo, Marcelino; Regino, Celeste A S et al. (2007) MR lymphangiography using dendrimer-based contrast agents: a comparison at 1.5T and 3.0T. Magn Reson Med 57:431-6
Kobayashi, Hisataka; Hama, Yukihiro; Koyama, Yoshinori et al. (2007) Simultaneous multicolor imaging of five different lymphatic basins using quantum dots. Nano Lett 7:1711-6
Kobayashi, Hisataka; Kawamoto, Satomi; Bernardo, Marcelino et al. (2006) 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. J Control Release 111:343-51

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