Elsevier

Journal of Controlled Release

Volume 138, Issue 2, 1 September 2009, Pages 90-102
Journal of Controlled Release

Review
Diagnostic nanocarriers for sentinel lymph node imaging

https://doi.org/10.1016/j.jconrel.2009.05.010Get rights and content

Abstract

In the last decade, methods for the precise localization of sentinel lymph node (SLN) have drawn tremendous attention by cancer surgeons and researchers in the field of medical diagnosis. The accurate identification and characterization of lymph nodes by imaging has important therapeutic and prognostic significance in patients with newly diagnosed cancers. The SLN is the first lymph node that receives lymphatic drainage from the site of a primary tumor. The sentinel node is much more likely to contain metastatic tumor cells than other lymph nodes in the same region. Amongst the various exploited methods for SLN diagnosis, nanocarriers have received increasing attention as lymph node delivery agents. The present review focuses on various such particulate carriers namely radiolabeled sulfur colloids, liposomes, quantum dots, dendrimers and magnetic nanoparticles, which are most extensively studied and have been attributed with the most desirable characteristics for SLN imaging.

Introduction

The presence of lymph node metastases has major prognostic implications in case of most of the malignancies [1], [2], [3], and is a major criterion for determining the need for adjuvant chemotherapy [4]. Studies concerning the involvement of lymphatic drainage in the treatment of cancer patients and its contribution towards enhancing their survival are not new. Investigation of cancer patients and careful scrutiny of the observations made during their subsequent follow-up sessions have lead to the proposition of various speculations concerning the dissemination of solid tumors.

Sentinel node imaging is the latest concept towards a better understanding and analysis of dissemination of solid tumors. The hypothesis emphasizing the involvement of lymphatic drainage in sequential dissemination of solid malignancies has stemmed from Halsted's theory and research conducted by Gilchrist, Zeidman and coworkers [5].

Cabanas, back in the year 1977, proposed the involvement of lymphatic system in sequential dissemination of primary tumor during his studies in patients with penile carcinoma [6], [7], [8]. He discovered that a specific lymph node in the groin, which remained constant in its location and which he consequently termed as the ‘sentinel node’, was the preferential drainage area of the cells of squamous cell carcinoma of the penis. During his research he realized that sentinel node was the first location of localization of tumor cells through lymphatics before their passage to the other nodes of the lymphatic drainage pathway. Thus he deduced that the status of the entire lymphatic system could be predicted via the identification, surgical dissection and subsequent histological examination of the sentinel node. Thus, the occurrence of metastatic disease in the sentinel node could be used as a possible indicator of spread of the disease in the other nodes of the region and hence dissection of the regional lymph nodes could be recommended. Likewise, absence of disease in the sentinel node would spare the patients of the trauma of dissection of other nodes of the particular region. Since then the sentinel lymph node (SLN), deemed as the first draining site of an anatomical region, has been regarded as a histological indicator of the absence of tumor metastases in the other non-SLNs [9], [10].

The general acceptance and extensive use of SLN imaging was triggered by the initiation of intraoperative lymphatic mapping in 1989. Ever since researchers all over the world have directed their work in this direction and technique validations have now led to SLNs being used as vital tools of providing critical information in patients showing signs of tumor metastasis to superficial lymph nodes. This has facilitated accurate determination of the stage of malignancy, without compromising the local control, at the same time providing the advantage of the patients being spared of regional lymph node dissection.

Section snippets

Lymphatic imaging through SLN biopsy

Visualization of lymphatic drainage began at the end of the eighteenth century when Sappey et al. attempted the imaging of the intricate lymphatic system of the breast using mercury injections. It was later described by Haagensen et al. [11] in ‘The Lymphatics in Cancer’, where he has described anatomical studies using injections of various tracer fluids. The book further described the use of vital dyes and radioactive isotopes being employed by surgeons and nuclear medicine physicians to

SLN imaging: current modalities

The development of a reliable technique for the evaluation of the lymphatic function for cancer patients is one of the most researched areas. Various methods are being practiced for the accurate evaluation of lymphatic function. These imaging modalities are listed in Table 1. The subsequent sections of this review focus on the non-invasive sentinel node imaging modalities and why they have gained a preference over the earlier used invasive techniques of sentinel lymph node mapping.

Liposomes

Liposomes have been used as delivery vehicles since the 1960s and their use for the delivery of imaging agents, for all imaging modalities, has a long history. Liposomes are defined as vesicles in which an aqueous volume is entirely surrounded by a phospholipid membrane. They can vary in size from 30 nm to several micrometers, and can be uni- or multilamellar. Their properties have been extensively investigated and can vary substantially with respect to their size, lipid composition, surface

Implications and future directions

Cancer is known to develop via a multistep carcinogenesis process. Cancer treatments are performed on the basis of clinical and pathologic staging that is determined using morphologic diagnostic tools, such as conventional radiological and histopathological examinations. SLN localization is one the most important parameters considered in cancer diagnosis and therapy. The concept of the sentinel lymph node has earned widespread importance with the advent of the sentinel lymph node biopsy

References (179)

  • A. Luciani et al.

    Lymph node imaging: basic principles

    Eur. J. Radiol.

    (2006)
  • G. Ege

    Lymphoscintigraphy—techniques and applications in the management of breast carcinoma

    Semin. Nucl. Med.

    (1983)
  • M.T. Ercan et al.

    Autoradiography of lymph nodes with Tc-99m-dextran in rabbits

    Nucl. Med. Biol.

    (1992)
  • K. Licha et al.

    Optical imaging in drug discovery and diagnostic applications

    Adv. Drug Deliv. Rev.

    (2005)
  • J.C. Wu et al.

    Noninvasive optical imaging of firefly luciferase reporter gene expression in skeletal muscles of living mice

    Molec. Ther.

    (2001)
  • N.J. Abbott et al.

    Delivery of imaging agents into brain

    Adv. Drug Deliv. Rev.

    (1999)
  • C.S. Cutler et al.

    Utilization of metabolic, transport and receptor-mediated processes to deliver agents for cancer diagnosis

    Adv. Drug Deliv. Rev.

    (1999)
  • C. Ke et al.

    Folate-receptor-targeted radionuclide imaging agents

    Adv. Drug Deliv. Rev.

    (2004)
  • W.C. Chan et al.

    Luminescent quantum dots for multiplexed biological detection and imaging

    Curr. Opin. Biotechnol.

    (2002)
  • J.V. Frangioni

    In vivo near-infrared fluorescence imaging

    Curr. Opin. Chem. Biol.

    (2003)
  • L. Ludemann et al.

    Pharmacokinetic analysis of glioma compartments with dynamic Gd–DTPA-enhanced magnetic resonance imaging

    Magn. Reson. Imaging

    (2000)
  • L.X. Tiefenauer et al.

    In vivo evaluation of magnetic nanoparticles for use as a tumor contrast agent in MRI

    Magn. Reson. Imaging

    (1996)
  • M. Hamoudeh et al.

    Radionuclides delivery systems for nuclear imaging and radiotherapy of cancer

    Adv. Drug Deliv. Rev.

    (2008)
  • H.E. Wang et al.

    Internal radiotherapy and dosimetric study for 111In/177Lu-pegylated liposomes conjugates in tumor-bearing mice

    Nucl. Instrum. Methods, A

    (2006)
  • S. Dagar et al.

    VIP grafted sterically stabilized liposomes for targeted imaging of breast cancer: in vivo studies

    J. Control. Release

    (2003)
  • V.P. Torchilin

    Surface-modified liposomes in γ and MR imaging

    Adv. Drug Deliv. Rev.

    (1997)
  • M.P. Osborne et al.

    Radionuclide-labelled liposomes — a new lymph node imaging agent

    Int. J. Nucl. Med. Biol.

    (1979)
  • H.M. Patel et al.

    Assessment of the potential uses of liposomes for lymphoscintigraphy and lymphatic drug delivery. Failure of 99m-technetium to represent intact liposomes in lymph nodes

    Biochim. Biophys. Acta

    (1984)
  • C. Tilcock et al.

    99mTc-labeling of lipid vesicles containing the lipophilic chelator PE-DTPA: effect of tin-to chelate ratio, chelate content and surface polymer on labeling efficiency and biodistribution behavior

    Nucl. Med. Biol.

    (1994)
  • L.A. Medina et al.

    Avidin/biotinliposome system injected in the pleural space for drug delivery to mediastinal lymph nodes

    J. Pharm. Sci.

    (2004)
  • L.A. Medina et al.

    Pharmacokinetics and biodistribution of [111ln]-avidin and [99mTc]-biotin-liposomes injected in the pleural space for the targeting of mediastinal nodes

    Nucl. Med. Biol.

    (2004)
  • K. Dowlatshahi et al.

    Lymph node micrometastases from breast carcinoma: reviewing the dilemma

    Cancer

    (1997)
  • B. Fisher et al.

    Relation of number of positive axillary nodes to the prognosis of patients with primary breast cancer. An NSABP update

    Cancer

    (1983)
  • A. Goldhirsch et al.

    Meeting highlights: international consensus panel on the treatment of primary breast cancer. Seventh international conference on adjuvant therapy of primary breast cancer

    J. Clin. Oncol.

    (2001)
  • P.J. Tanis et al.

    History of sentinel node and validation of the technique

    Breast Cancer Res.

    (2001)
  • R.M. Cabanas

    An approach for the treatment of penile carcinoma

    Cancer

    (1977)
  • C.D. Haagensen et al.
  • D.L. Morton et al.

    Technical details of intraoperative lymphatic mapping for early stage melanoma

    Arch. Surg.

    (1992)
  • D.S. Reintgen et al.

    The orderly progression of melanoma nodal metastases

    Ann. Surg.

    (1994)
  • A.E. Giuliano et al.

    Lymphatic mapping and sentinel lymphadenectomy for breast cancer

    Ann. Surg.

    (1994)
  • D.N. Krag et al.

    Surgical resection and radiolocalization of the sentinel lymph node in breast cancer using a gamma probe

    Surg. Oncol.

    (1993)
  • C.A. Perez et al.

    Carcinoma of prostate

  • C. Parsons

    Radiology in oncology

  • J.B. Kimmouth

    Lymphangiography in man: method outlining lymphatic trunks at operation

    Clin. Sci.

    (1952)
  • S.V. Lossef

    Complications of lymphography

    Semin. Intervent. Radiol.

    (1994)
  • S.E. Strand et al.

    Radiolabeled colloids and macromolecules in the lymphatic system

    Crit. Rev. Ther. Drug Carr. Syst.

    (1989)
  • F. Ikomi et al.

    Mechanism of colloidal particle uptake into the lymphatic system—basic study with percutaneous lymphography

    Radiology

    (1995)
  • T.J. Vogel et al.

    Contrast-enhanced lymphography—CT or MR imaging?

    Acta Radiol.

    (1997)
  • G.D. Robinson et al.

    Imaging of lymph node uptake after intravenous administration of indium-111 metalloporphyrins

    J. Nucl. Med.

    (1986)
  • S.G. Demos et al.

    Deep subsurface imaging in tissues using spectral and polarization filtering

    Opt. Express

    (2001)
  • Cited by (82)

    • Advances in the clinical translation of nanotechnology

      2017, Current Opinion in Biotechnology
    • Radiolabeled γ-polyglutamic acid complex as a nano-platform for sentinel lymph node imaging

      2014, Journal of Controlled Release
      Citation Excerpt :

      Radioactivity in the other tissue including liver, spleen, and kidneys was low, suggesting the low leakage to the capillary vessels. At present, nanoparticle-based probes including 99mTc-labeled tin colloid and sulfur colloid are in clinical use for sentinel lymph node imaging [24]. However, it is difficult for 99mTc-labeled tin colloid and sulfur colloid to be modified to aim at multimodality imaging.

    View all citing articles on Scopus
    View full text