Breast Cancer Research and Treatment

, Volume 103, Issue 1, pp 23–28 | Cite as

Simultaneous two-color spectral fluorescence lymphangiography with near infrared quantum dots to map two lymphatic flows from the breast and the upper extremity

  • Yukihiro Hama
  • Yoshinori Koyama
  • Yasuteru Urano
  • Peter L. Choyke
  • Hisataka KobayashiEmail author
Preclinical Study


Due to their small size and poor access, the lymphatic function has been difficult to study in vivo. Especially difficult is the mapping of lymphatic drainage from two basins into the same node. Quantum dots can be used to perform multicolor images with high fluorescent intensity and are of a nano-size size suitable for lymphatic imaging via direct interstitial injection. Here we show simultaneous two-color in vivo wavelength-resolved spectral fluorescence lymphangiography using two near infrared quantum dots with different emission spectra, which allow non-invasive and simultaneous visualization of two separate lymphatic flows draining the breast and the upper extremity and variations in the drainage patterns and the water sheds within the axillary node. Two-color spectral fluorescence lymphangiography can provide insight into mechanisms of drainage from different lymphatic basins that may lead to sentinel lymph nodes detection of the breast cancer as well as prevention of complications such as lymphedema of the arm.


Lymphatic drainage Imaging Breast cancer Lymph node Lymphedema Nanotechnology Quantum dots Spectral fluorescence imaging Near infrared 


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This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.


  1. 1.
    Goldman ER, Clapp AR, Anderson GP, Uyeda HT, Mauro JM, Medintz IL, Mattoussi H (2004) Multiplexed toxin analysis using four colors of quantum dot fluororeagents. Anal Chem 76:684–688PubMedCrossRefGoogle Scholar
  2. 2.
    Kobayashi H, Kawamoto S, Choyke PL, Sato N, Knopp MV, Star RA, Waldmann TA, Tagaya Y, Brechbiel MW (2003) Comparison of dendrimer-based macromolecular contrast agents for dynamic micro-magnetic resonance lymphangiography. Magn Reson Med 50:758–766PubMedCrossRefGoogle Scholar
  3. 3.
    Kobayashi H, Kawamoto S, Bernardo M, Brechbiel MW, Knopp MV, Choyke PL (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 111:343–351PubMedCrossRefGoogle Scholar
  4. 4.
    Kim S, Lim YT, Soltesz EG, De Grand AM, Lee J, Nakayama A, Parker JA, Mihaljevic T, Laurence RG, Dor DM, Cohn LH, Bawendi MG, Frangioni JV (2004) Near-infrared fluorescent type II quantum dots for sentinel lymph node mapping. Nat Biotechnol 22:93–97PubMedCrossRefGoogle Scholar
  5. 5.
    Gao X, Cui Y, Levenson RM, Chung LW, Nie S (2004) In vivo cancer targeting and imaging with semiconductor quantum dots. Nat Biotechnol 22:969–976PubMedCrossRefGoogle Scholar
  6. 6.
    Kobayashi H, Kawamoto S, Sakai Y, Choyke PL, Star RA, Brechbiel MW, Sato N, Tagaya Y, Morris JC, Waldmann TA (2004) Lymphatic drainage imaging of breast cancer in mice by micro-magnetic resonance lymphangiography using a nano-size paramagnetic contrast agent. J Natl Cancer Inst 96:703–708PubMedCrossRefGoogle Scholar
  7. 7.
    Kobayashi H, Brechbiel MW (2005) Nano-sized MRI contrast agents with dendrimer cores. Adv Drug Deliv Rev 57:2271–2286PubMedCrossRefGoogle Scholar
  8. 8.
    Morrell RM, Halyard MY, Schild SE, Ali MS, Gunderson LL, Pockaj BA (2005) Breast cancer-related lymphedema. Mayo Clin Proc 80:1480–1484PubMedCrossRefGoogle Scholar
  9. 9.
    Petrek JA, Senie RT, Peters M, Rosen PP (2001) Lymphedema in a cohort of breast carcinoma survivors 20 years after diagnosis. Cancer 92:1368–1377PubMedCrossRefGoogle Scholar
  10. 10.
    Purushotham AD, Upponi S, Klevesath MB, Bobrow L, Millar K, Myles JP, Duffy SW (2005) Morbidity after sentinel lymph node biopsy in primary breast cancer: results from a randomized controlled trial. J Clin Oncol 23:4312–4321PubMedCrossRefGoogle Scholar
  11. 11.
    Erickson VS, Pearson ML, Ganz PA, Adams J, Kahn KL (2001) Arm edema in breast cancer patients. J Natl Cancer Inst 93:96–111PubMedCrossRefGoogle Scholar
  12. 12.
    McMasters KM, Tuttle TM, Carlson DJ, Brown CM, Noyes RD, Glaser RL, Vennekotter DJ, Turk PS, Tate PS, Sardi A, Cerrito PB, Edwards MJ (2000) Sentinel lymph node biopsy for breast cancer: a suitable alternative to routine axillary dissection in multi-institutional practice when optimal technique is used. J Clin Oncol 18:2560–2566PubMedGoogle Scholar
  13. 13.
    Scoggins CR, Chagpar AB, Martin RC, McMasters KM (2005) Should sentinel lymph-node biopsy be used routinely for staging melanoma and breast cancers? Nat Clin Pract Oncol 2:448–455PubMedCrossRefGoogle Scholar
  14. 14.
    Giuliano AE, Haigh PI, Brennan MB, Hansen NM, Kelley MC, Ye W, Glass EC, Turner RR (2000) Prospective observational study of sentinel lymphadenectomy without further axillary dissection in patients with sentinel node-negative breast cancer. J Clin Oncol 18:2553–2559PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2006

Authors and Affiliations

  • Yukihiro Hama
    • 1
  • Yoshinori Koyama
    • 1
  • Yasuteru Urano
    • 2
  • Peter L. Choyke
    • 1
  • Hisataka Kobayashi
    • 1
    Email author
  1. 1.Molecular Imaging Program, Center for Cancer for Cancer ResearchNational Cancer InstituteBethesdaUSA
  2. 2.Graduate School of Pharmaceutical SciencesThe University of TokyoTokyoJapan

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