Breast Cancer

, Volume 15, Issue 2, pp 145–152 | Cite as

In vivo single molecular imaging and sentinel node navigation by nanotechnology for molecular targeting drug-delivery systems and tailor-made medicine

  • Motohiro Takeda
  • Hiroshi Tada
  • Hideo Higuchi
  • Yoshio Kobayashi
  • Masaki Kobayashi
  • Yuu Sakurai
  • Takanori Ishida
  • Noriaki Ohuchi
Conference Paper Presidential symposium: Individualized diagnosis for tailored treatment of breast cancer


The recent advances in nanotechnology have a great potential to improve the prevention, diagnosis, and treatment of human diseases. Nanomaterials for medical applications are expected to grasp pharmacokinetics and the toxicity for application to medical treatment on the aspect of safety of the nanomaterials and nanodevices. We describe a generation of CdSe nanoparticles [quantum dots (QDs)] conjugated with monoclonal anti-HER2 antibody (Trastuzumab), for single molecular in vivo imaging of breast cancer cells. We established a high-resolution in vivo 3D microscopic system for a novel imaging method at the molecular level. The cancer cells expressing HER2 protein were visualized by the nanoparticles in vivo at subcellular resolution, suggesting future utilization of the system in medical applications to improve drug-delivery systems to target the primary and metastatic tumors for made-to-order treatment. We also describe sentinel node navigation using fluorescent nanoparticles for breast cancer surgery in experimental model, which have shown the potential to be an alternative to existing tracers in the detection of the sentinel node if we select the appropriate particle size and wavelength. Future innovation in cancer imaging by nanotechnology and novel measurement technology will provide great improvement, not only in the clinical field but also in basic medical science for the development of medicine.


Single molecular imaging Sentinel lymph node biopsy Nanomedicine Breast cancer HER2 


  1. 1.
    Torchilin VP, Lukyanov AN, Gao Z, Papahadjopoulos-Sternberg B. Immunomicelles: targeted pharmaceutical carriers for poorly soluble drugs. Proc Natl Acad Sci USA. 2003;100:6039–44.PubMedCrossRefGoogle Scholar
  2. 2.
    Krauss WC, Park JW, Kirpotin DB, Hong K, Benz CC. Emerging antibody-based HER2 (ErbB-2/neu) therapeutics. Breast Dis. 2000;11:113–24.PubMedGoogle Scholar
  3. 3.
    Lyons SK. Advances in imaging mouse tumour models in vivo. J Pathol. 2005;205:194–205.PubMedCrossRefGoogle Scholar
  4. 4.
    Ishijima A, Kojima H, Funatsu T, Tokunaga M, Higuchi H, Tanaka H. Simultaneous observation of individual ATPase, mechanical events by a single myosin molecule during interaction with actin. Cell. 1998;92:161–71.PubMedCrossRefGoogle Scholar
  5. 5.
    Wu X, Liu H, Liu J, Haley KN, Treadway JA, Larson JP. Immunofluorescent labeling of cancer marker Her2, other cellular targets with semiconductor quantum dots. Nat Biotechnol. 2003;21:41–6.PubMedCrossRefGoogle Scholar
  6. 6.
    Gao X, Cui Y, Levenson RM, Chung LW, Nie S. In vivo cancer targeting, imaging with semiconductor quantum dots. Nat Biotechnol. 2004;22:969–76.PubMedCrossRefGoogle Scholar
  7. 7.
    Yildiz A, Forkey JN, McKinney SA, Ha T, Goldman YE, Selvin PR. Myosin V walks hand-over-hand: single fluorophore imaging with 1.5-nm localization. Science. 2003;300:2061–5.PubMedCrossRefGoogle Scholar
  8. 8.
    Dahan M, Levi S, Luccardini C, Rostaing P, Riveau B, Triller A. Diffusion dynamics of glycine receptors revealed by single-quantum dot tracking. Science. 2003;302:442–5.PubMedCrossRefGoogle Scholar
  9. 9.
    Lidke DS, Nagy P, Heintzmann R, Arndt-Jovin DJ, Post JN, Grecco HE, Jares-Erijman EA, Jovin TM. Quantum dot ligands provide new insights into erbB/HER receptor-mediated signal transduction. Nat Biotechnol. 2004;22:198–203.PubMedCrossRefGoogle Scholar
  10. 10.
    Krag DN, Weaver DL, Alex JC. Surgical resection and radio-localization of the sentinel node in breast cancer using a gamma probe. Surg Oncol. 1993;2:335–40.PubMedCrossRefGoogle Scholar
  11. 11.
    Tafra L, Lannin DR, Swanson MS. Multicenter trial of sentinel node biopsy for breast cancer using both technetium sulfur colloid and isosulfan blue dye. Ann Surg. 2001;233:51–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Kurebayashi J, Otsuki T, Tang CK, Kurosumi M, Yamamoto S, Tanaka K, Mochizuki M, Nakamura H, Sonoo H. Isolation and characterization of a new human breast cancer cell line, KPL-4, expressing the Erb B family receptors and interleukin-6. Br J Cancer. 1999;79:707–17.PubMedCrossRefGoogle Scholar
  13. 13.
    Leunig M, Yuan F, Menger MD, Boucher Y, Goetz AE, Messmer K, Jain RK. Angiogenesis, microvascular architecture, microhemodynamics, and interstitial fluid pressure during early growth of human adenocarcinoma LS174T in SCID mice. Cancer Res. 1992;52:6553–60.PubMedGoogle Scholar
  14. 14.
    Braun RD, Abbas A, Bukhari SO, Wilson W III. Hemodynamic parameters in blood vessels in choroidal melanoma xenografts and rat choroid. Invest Ophthalmol Vis Sci. 2002;43:3045–52.PubMedGoogle Scholar
  15. 15.
    Carraway CA, Carvajal ME, Carraway KL. Association of the Ras to mitogen-activated protein kinase signal transduction pathway with microfilaments. Evidence for a p185 (neu)-containing cell surface signal transduction particle linking the mitogenic pathway to a membrane-microfilament association site. J Biol Chem. 1999;274:25659–67.PubMedCrossRefGoogle Scholar
  16. 16.
    Buss F, Arden SD, Lindsay M, Luzio JP, Kendrick-Jones J. Myosin VI isoform localized to clathrin-coated vesicles with a role in clathrin-mediated endocytosis. EMBO J. 2001;20:3676–84.PubMedCrossRefGoogle Scholar
  17. 17.
    Kamal A, Goldstein LS. Connecting vesicle transport to the cytoskeleton. Curr Opin Cell Biol. 2000;12:503–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Mross K, Niemann B, Massing U, Drevs J, Unger C, Bhamra R, Swenson CE. Pharmacokinetics of liposomal doxorubicin (TLC-D99; Myocet) in patients with solid tumors: an open-label, single-dose study. Cancer Chemother Pharmacol. 2004;54:514–24.PubMedCrossRefGoogle Scholar
  19. 19.
    O’Brien ME, Wigler N, Inbar M, Rosso R, Grischke E, Santoro A. Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Ann Oncol. 2004;15:440–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Hamaguchi T, Matsumura Y, Nakanishi Y, Muro K, Yamada Y, Shimada Y. Antitumor effect of MCC-465, pegylated liposomal doxorubicin tagged with newly developed monoclonal antibody GAH, in colorectal cancer xenografts. Cancer Sci. 2004;95:608–13.PubMedCrossRefGoogle Scholar
  21. 21.
    Park JW, Kirpotin DB, Hong K, Shalaby R, Shao Y, Nielsen UB. Tumor targeting using anti-her2 immunoliposomes. J Control Release. 2001;74:95–113.PubMedCrossRefGoogle Scholar
  22. 22.
    Josephson L, Mahmood U, Wunderbaldinger P, Tang Y, Weissleder R. Pan and sentinel lymph node visualization using a near-infrared fluorescent probe. Mol Imaging. 2003;2:18–23.PubMedCrossRefGoogle Scholar
  23. 23.
    Patrick W, Karl T, Chrstoph B. Near-infrared fluorescence imaging of lymph nodes using a new enzyme sensing activatable macromolecular optical probe. Eur Radiol. 2003;13:2206–11.CrossRefGoogle Scholar
  24. 24.
    Kobayashi M, Mizumoto T, Shibuya Y, Takeda M, Enomoto M. Fluorescence tomography in turbid media based on acousto-optic modulation imaging. Appl Phys Lett. 2006;89:181102.CrossRefGoogle Scholar

Copyright information

© The Japanese Breast Cancer Society 2008

Authors and Affiliations

  • Motohiro Takeda
    • 1
    • 2
  • Hiroshi Tada
    • 1
  • Hideo Higuchi
    • 3
  • Yoshio Kobayashi
    • 4
  • Masaki Kobayashi
    • 5
  • Yuu Sakurai
    • 1
  • Takanori Ishida
    • 1
  • Noriaki Ohuchi
    • 1
  1. 1.Department of Surgical Oncology, Graduate School of MedicineTohoku UniversitySendaiJapan
  2. 2.Department of Bioengineering and Robotics, Graduate School of EngineeringTohoku UniversitySendaiJapan
  3. 3.Biomedical Engineering Research OrganizationTohoku University, SendaiSendaiJapan
  4. 4.Department of Biomolecular Functional Engineering, College of EngineeringIbaraki UniversityHitachiJapan
  5. 5.Division of ElectronicsTohoku Institute of TechnologySendaiJapan

Personalised recommendations