WO2002088666A2 - Method for identifying lymph nodes - Google Patents

Method for identifying lymph nodes Download PDF

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Publication number
WO2002088666A2
WO2002088666A2 PCT/US2002/013524 US0213524W WO02088666A2 WO 2002088666 A2 WO2002088666 A2 WO 2002088666A2 US 0213524 W US0213524 W US 0213524W WO 02088666 A2 WO02088666 A2 WO 02088666A2
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method
dye
lymph nodes
composition
animal
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PCT/US2002/013524
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French (fr)
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WO2002088666A3 (en )
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Jonathan C. Salo
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Loma Linda University Surgery Medical Group, Inc.
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K49/00Preparations for testing in vivo
    • A61K49/001Preparation for luminescence or biological staining
    • A61K49/0063Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres
    • A61K49/0069Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres the agent being in a particular physical galenical form
    • A61K49/0076Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres the agent being in a particular physical galenical form dispersion, suspension, e.g. particles in a liquid, colloid, emulsion
    • A61K49/0084Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres the agent being in a particular physical galenical form dispersion, suspension, e.g. particles in a liquid, colloid, emulsion liposome, i.e. bilayered vesicular structure
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K49/00Preparations for testing in vivo
    • A61K49/001Preparation for luminescence or biological staining
    • A61K49/0013Luminescence
    • A61K49/0017Fluorescence in vivo
    • A61K49/0019Fluorescence in vivo characterised by the fluorescent group
    • A61K49/0021Fluorescence in vivo characterised by the fluorescent group the fluorescent group being a small organic molecule
    • A61K49/0041Xanthene dyes, used in vivo, e.g. administered to a mice, e.g. rhodamines, rose Bengal
    • A61K49/0043Fluorescein, used in vivo
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/10Dispersions; Emulsions
    • A61K9/127Liposomes

Abstract

A method for locating the lymph nodes draining a specific anatomic area in a human or animal comprising administering one or more than one composition comprising liposomes and a dye, allowing the liposomes comprising the dye to be taken into the lymph nodes draining the anatomic area, and imaging the dye, thereby locating the lymph nodes.

Description

METHOD FOR IDENTIFYING LYMPH NODES

CROSS-REFERENCE TO RELATED APPLICATIONS

The present Application claims the benefit of United States provisional patent application 60/287,834, titled "Method For Locating a Sentinel Lymph Node," filed May 1, 2001 the contents of which are incorporated in this disclosure by reference in its entirety. BACKGROUND

There are a variety of reasons for determining the location of lymph nodes draining a specific anatomic area. These reasons include basic research into the structure and function of the lymphatic system. Additionally, metastases to regional lymph nodes are a major risk factor for metastatic spread beyond the primary site of a tumor. Therefore, the staging of many types of malignancies is partly based on the presence or absence of metastases in regional lymph nodes.

Generally, the presence or absence of metastases in regional lymph nodes is usually determined by sampling lymph nodes in the area of regional lymph drainage from the site of the primary malignancy. Such sampling has two disadvantages. First, it is possible to obtain a false negative result of lymph node involvement by sampling uninvolved lymph nodes more distal in the lymphatic chain while not sampling involved lymph nodes more proximal in the lymphatic chain to the site of the primary malignancy. Second, random sampling of lymph nodes usually involves significant tissue dissection that can damage adjacent structures. In order to address these disadvantages, methods were developed to biopsy the sentinel lymph node draining an anatomic area, that is, the proximal-most or first lymph nodes encountered by lymph flow from an anatomic area. It is assumed that, if there are no metastases in the sentinel lymph node, then there was no need to sample other regional lymph nodes.

A sentinel lymph node biopsy requires that the sentinel lymph node first be located. One method of locating the sentinel lymph node is by mapping the regional lymphatic system using isosulfan blue, a lymphotropic vital dye, that allows visual identification of the regional lymph nodes. Unfortunately, use of this dye still requires extensive dissection of tissue to locate the lymph nodes containing the dye. Even with extensive dissection, however, published clinical series using isosulfan blue indicate that the sentinel lymph node was located in only about 65 % of cases. Another method of locating the sentinel lymph node is by lymphoscintigraphy utilizing a detectible radioactive tracer, such as technecium-99 labeled sulfur colloid, that is injected into an anatomic area and that travels through lymphatics to the draining lymph nodes. This method can both identify lymph nodes drained by an anatomic area, and also the sentinel lymph node. However, the success rate of this method is highly variable because it is very dependent on the skill of the surgeon. Further, the use of lymphoscintigraphy requires expensive specialized instruments and involves the use of ionizing radiation that poses a potential risk to surgical team members and to the patient.

Therefore, there is a need for a method for locating the lymph nodes draining a specific anatomic area in a human or animal that is not associated with these disadvantages. Further, there is a need for a method for determining the stage of disease in a patient with a malignancy more accurately that using random lymph node sampling.

SUMMARY In one embodiment, the present invention is a method for locating the lymph nodes draining a specific anatomic area in a human or animal. The method comprises, first, administering to the human or animal one or more than one composition comprising liposomes. The liposomes comprise one or more than one dye. Next, the composition is allowed to be taken into the lymph nodes draining the anatomic area, thereby resulting in lymph nodes containing the dye. Then, the dye is imaged, thereby locating the lymph nodes. The method can further comprise providing the one or more than one composition before administering the composition.

In one embodiment, the liposomes comprise one or more than one type of lipid selected from the group consisting of 1,2 dipalmitoyl-sn-glycero-3-phosphocholine, phosphatidylcholine, phosphatidylglycerol, phosphatidylemanolamine and cholesterol. In another embodiment, the dye is selected from the group consisting of fluorescein, indocyanine green, indigo carmine and eosin yellow. In a preferred embodiment, the dye is a fluorescent dye.

In one embodiment, the composition is administered in a dose of between about 5 mg and about 1000 mg per square meter of body surface area of the human or animal. In another embodiment, the composition is administered in a dose of between about 10 mg and about 100 mg per square meter of body surface area of the human or animal. In a preferred embodiment, the composition is administered in a dose of about 50 mg per square meter of body surface area of the human or animal.

In one embodiment, the composition is administered by a route selected from the group consisting of intradermal administration, intramuscular administration, subcutaneous administration, transdermal administration, administration into the breast parenchyma, adniinistration into a subserosal surface of the gastrointestinal tract, intraperitoneal administration, mtraluminal administration into the gastrointestinal tract and direct adniinistration into the substance of a malignant neoplasm. In another embodiment, imaging the dye comprises exciting the dye using electromagnetic radiation. In a preferred embodiment, imaging the dye comprises exciting the dye using electromagnetic radiation in the visible spectrum. In another preferred embodiment, imaging the dye comprises exciting the dye using electromagnetic radiation in the infrared spectrum. In one embodiment, imaging the dye comprises visualization of the dye, such as through intact skin.

In one embodiment, the present invention is a method for determining the presence or absence of malignant cells in lymph nodes of a patient with a malignancy draining the anatomic area where the malignancy is located. The method comprises, first, selecting a patient with a malignancy having the potential of lymphatic metastases. Next, the method comprises locating the lymph nodes draining the anatomic area where the malignancy is located according to the present invention. Then, at least part of one or more than one of the lymph nodes located are removed and examined histologically for the presence or absence of malignant cells. In a preferred embodiment, at least part of one or more than one of the lymph nodes lymph node removed is at least part of a sentinel lymph node.

In one embodiment, the present invention is a method for determining the stage of disease in a patient with a malignancy. The method comprises, first, determining the presence or absence of malignant cells in lymph nodes of the patient according to the present invention. Next, staging protocols for the type of malignancy are referred to, where the absence of malignant cells in the lymph nodes of the patient indicates a first stage of the malignancy and where the presence of malignant cells in the lymph nodes of the patient indicates a second stage of the malignancy.

In another embodiment, the present invention is a method for treating a patient with a malignancy. The method comprises, first, determining that malignant cells are present in the lymph nodes of the patient according to the present invention. Then, a therapeutic action is taken based on the presence of malignant cells in the lymph nodes. In one embodiment, the therapeutic action is selected from the group consisting of administering a chemotherapeutic agent to the patient, administering heat or cold to the patient, and administering ionizing radiation to the patient. The chemotherapeutic agent can be selected from the group consisting of a cytotoxic agent, a hormonal agent and an immunotherapy agent. The therapeutic action can also comprise surgical removal of at least part of the regional lymph nodes draining the area of the malignancy.

In one embodiment, the present invention is a kit for locating the lymph nodes draining a specific anatomic area in a human or animal. The kit comprises one or more than one container containing a composition comprising liposomes and one or more than one dye. The kit can also comprise instructions for performing the method of the present invention, one or more than one instrument for administering the composition to the human or animal or one or more than one instrument for imaging the dye present in the composition.

DESCRIPTION According to one embodiment of the present invention, there is provided a method for locating the lymph nodes draining a specific anatomic area in a human or animal. The method comprises administering to the human or animal one or more than one composition comprising liposomes, where the liposomes comprise one or more than one dye, allowing the liposomes comprising the dye to be taken into the lymph nodes draining the anatomic area, and imaging the dye, thereby locating the lymph nodes. According to another embodiment, there is provided a method for determining the presence or absence of malignant cells in the lymph nodes of a patient with a malignancy. According to another embodiment of the present invention, there is provided a method for determining the stage of disease in a patient with a malignancy. According to another embodiment of the present invention, there is provided a method for treating a patient with a malignancy. According to another embodiment of the present invention, there is provided a kit for locating the lymph nodes draining a specific anatomic area in a human or animal. The methods and kit of the present invention will now be disclosed in detail.

As used in this disclosure, a "sentinel lymph node," also known as the "first echelon node," is defined as a regional lymph node first encountered by lymphatics draining from a particular anatomic area. As will be understood by those with skill in the art with reference to this disclosure, the "sentinel lymph node" can be a plurality of anatomically or histologically separate lymph nodes. As used in this disclosure, the "second eschelon node," is defined as the regional lymph node or regional lymph nodes that drain the sentinel lymph node.

In one embodiment, the present invention is a method for locating the lymph nodes draining a specific anatomic area in a human or animal. Among other uses, the method can be used to perform anatomic studies on the lymphatic system, or can be used as to determine the stage of a malignancy in a patient, or can be used to determine whether lymphatics draining a particular anatomic area should be removed as part of treatment of a malignancy.

The method for locating the lymph nodes draining a specific anatomic area in a human or animal comprises providing one or more than one composition comprising liposomes. Suitable liposomes comprise one or more than one type of lipid selected from the group consisting of 1,2 dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) (available from Avanti Polar Lipids, Inc., Alabaster, AL US), phosphatidylcholine, phosphatidylglycerol, phosphatidylemanolamine and cholesterol, though other lipids can also be used as will be understood by those with skill in the art with reference to this disclosure, such as phospholipids corresponding to the above listed phospholipids but with hydrophobic chains of varying lengths.

The liposomes further comprise one or more than one biocompatible dye that is capable of being incorporated into liposomes. In a preferred embodiment, the dye can be identified directly with the naked eye. In another preferred embodiment, the dye can be identified after causing the dye to fluoresce with either the naked eye or the use of an imaging device such as a charged coupled display (CCD) camera. In a particularly preferred embodiment, the dye is a fluorescent dye that has both excitation and emission wavelengths in the visible spectrum or in the near infrared. Suitable dyes include one or more than one dyes selected from the group consisting of fluorescein (Alcon Laboratories, Fort Worth, TX US), indocyanine green (Akorn Incorporated, Buffalo Grove, IL US), indigo carmine

(Consolidated Midland, Brewster, NY US), eosin yellow (Sigma Chemical, St. Louis, MO US) though other dyes can also be used as will be understood by those with skill in the art with reference to this disclosure.

The dye is incorporated into liposomes to produce the composition used in the present methods according to techniques that will be understood by those with skill in the art with reference to this disclosure. For example, a suitable composition for use in the present methods was made by incorporating fluorescein into DPPC by combining 1.25 ml of a 20 mg/ml solution of DPPC with 0.139 ml of methanol, and reducing the solution to dryness under argon stream in a 4 ml vial. Next, a suspension was created by adding 1 ml of 10% fluorescein solution, and the suspension was agitated in a tabletop vortexer for 45 minutes. The suspension was then heated to 45 °C, and extruded through a O.lμm polycarbonate filter (Avanti® Mini-Extruder, Avanti Polar Lipids, Inc.) 10 times. The solution was washed with an excess of phosphate buffered saline pH 7.4 (Sigma Chemical, St. Louis, MO US) and centrifuged at 15,000 rpm in a tabletop microfuge. The liposome suspension was washed three additional times with phosphate buffered saline resulting in about 0.55 ml of composition comprising a lipid concentration of about 45 mg per ml. After providing a suitable composition, the method for locating the lymph nodes comprises administering the composition to the human or animal in a suitable dose and through a suitable route. As a first approximation, the dose of composition administered is preferably between about 5 mg and about 1000 mg per square meter of body surface area. In another preferred embodiment, the dose administered is between about 10 mg and about 500 mg per square meter of body surface area. In a particularly preferred embodiment, the dose administered is about 100 mg per square meter of body surface area. However, optimal dose is also dependent on the anatomic area whose lymphatic system is being imaged. For example, when imaging the lymphatic system draining the upper outer quadrant of the human breast requires only about one third the dose for imaging the inner outer quadrant of the human breast.

Administration of the composition can be by any suitable route that allows uptake of the composition by the lymphatic system draining the anatomic area. Suitable routes include intradermal administration, intramuscular administration, subcutaneous administration, transdermal administration, administration into the breast parenchyma, administration into a subserosal surface of the gastrointestinal tract, intraperitoneal administration, intraluminal adniinistration into the gastrointestinal tract (such as intraoral), and direct administration into the substance of a malignant neoplasm in a patient, though other routes are also suitable as will be understood by those with skill in the art with reference to this disclosure. After the composition is administered, the composition is allowed to enter the lymphatic system draining the anatomic area, thereby passing into the sentinel lymph node, and further into the second and higher echelon nodes.

Next, the dye is imaged with the lymphatic system, allowing identification of the lymphatic system draining the anatomic area. In a preferred embodiment, imaging the dye allows identification of the sentinel lymph node draining the anatomic area. The sentinel node is considered to be the draining lymph node that is closest to the site of administration of the composition. In a particularly preferred embodiment, imaging the dye allows visualization of the dye either directly with the naked eye, or after causing the dye to fluoresce with the naked eye or with the use of an imaging device. In one embodiment, the dye can be imaged within a surgical field after dissection and mobilization of lymphatic tissue. In another particularly preferred embodiment, the dye can be imaged through intact skin. The mechanism for imaging the dye depends on the type of dye used, as will be understood by those with skill in the art with reference to this disclosure. In a preferred embodiment, imaging the dye comprises exciting the anatomic area comprising the lymph nodes containing the dye. Excitation can be performed using electromagnetic radiation. In one embodiment, the electromagnetic radiation is in the visible wavelengths. In another embodiment, the electromagnetic radiation is in the infrared wavelengths. The electromagnetic radiation can be either in a broad spectrum or in a narrow spectrum. Further, excitation can be performed using conventional incandescent or fluorescent light sources with the use of a narrow bandpass filter, or using a solid-state light source such as a light-emitting diode or diode laser, though other sources of excitation can also be used, as will be understood by those with skill in the art with reference to this disclosure. In one embodiment, excitation is performed using a fiberoptic light surgical headlight (Ultralight®, Luxtec, West Boylston, MA US). In a preferred embodiment, excitation is performed using a sterile fiberoptic cable with an angled or straight termination (Dolan-Jenner Industries, St. Lawrence, MA US), because a sterile fiberoptic light source can transilluminate tissue by directly applying the fiber optic cable to the skin or tissue overlying the regional lymph nodes draining an anatomic area.

Imaging the dye further comprises, detecting emission of the dye. In one embodiment, emission is detected using the naked eye. In another embodiment, emission is detected using an appropriate detector. In a preferred embodiment, detection comprises using appropriate filters, such as a narrow bandpass interference filter, that eliminate wavelengths of light other than those wavelengths at or near the emission peak of the dye.

For example, when the composition comprises a fluorescent dye, imaging the dye comprises exciting the fluorescent dye using suitable energy and detecting fluorescence of the dye. In a preferred embodiment, the fluorescence can be viewed through the intact skin without surgical dissection. For example, the fluorescent dye indocyanine green has an emission wavelength of about 825 nm and can be imaged through intact skin using an infrared detection device, such as a Night Quest™ PVS-14 (ITT Industries, Roanoke, VA US). Also for example, the fluorescent dye fluorescein has an emission wavelength in the visible spectrum of about 520 nm and can be imaged through intact skin by the naked eye.

In another embodiment, the present invention is a method for determining the presence or absence of malignant cells in lymph nodes of a patient with a malignancy. The method comprises selecting a patient with a malignancy having the potential of lymphatic metastases. Next, the lymph nodes draining the area of the malignancy are located according to the method of the present invention. Then, at least part of one or more than one of the lymph nodes located are removed and are examined histologically for the presence or absence of malignant cells. In a preferred embodiment, the sentinel lymph node is identified as the draining lymph node that is closest to the site of administration of the composition, and at least part of the sentinel lymph node is removed and examined histologically for the presence or absence of malignant cells.

In another embodiment, the present invention is a method for deteririining the stage of disease in a patient with a malignancy. The method comprises determining the presence or absence of malignant cells in lymph nodes of a patient with a malignancy according to the present invention. Next, the stage of the malignancy is determined by referring to staging protocols for the specific type of malignancy, where the absence of malignant cells in the lymph nodes of the patient indicates a first stage of the malignancy and the presence of malignant cells in the lymph nodes of the patient indicates a second stage of the malignancy. For example, according to the standard protocols for staging malignant melanoma, a tumor less then 1.5 mm thick without lymph node metastases is Stage I, while a tumor of the same thickness with a lymph node metastasis is considered Stage III. Similarly, according to the standard protocols for staging breast cancer, a primary tumor less than 2.0 cm and without lymph node metastases is considered Stage I, while a tumor of the same size with a lymph node metastasis is considered Stage IIA.

In another embodiment, the present invention is a method for treating a patient with a malignancy. The method comprises determining the presence or absence of malignant cells in lymph nodes of a patient with a malignancy according to the present invention. If malignant cells are present in the lymph nodes, one or more than one appropriate therapeutic action is taken. The action can include one or more than one action selected from the group consisting of administering a chemotherapeutic agent to the patient, such as cytotoxic agents or hormonal agents or immunotherapy agents, administering heat or cold to the patient, and administering ionizing radiation to the patient. The action can also include surgical removal of at least part of the regional lymph nodes draining the area of the malignancy.

In another embodiment, the present invention is a kit for locating the lymph nodes draining a specific anatomic area in a human or animal. The kit comprises one or more than one container containing a composition for use in the method according to the present invention for locating the lymph nodes draining a specific anatomic area in a human or animal. In one embodiment, the kit comprises instructions for performing one or more than one method according to the present invention. Preferably, the instructions are written instructions. However, the instructions can also be on video tape, audio tape, computer readable media or other perceivable media, as will be understood by those with skill in the art with reference to this disclosure. In another embodiment, the kit comprises instruments for administering the composition according to the present invention, such as a syringe with hypodermic needle. In another embodiment, the kit comprises one or more than one instrument for imaging the dye present in the composition, such as a source of electromagnetic radiation, an instrument for guiding electromagnetic radiation onto a surgical field or a viewing device, as will be understood by those with skill in the art with reference to this disclosure.

EXAMPLE I METHOD FOR LOCATING THE LYMPH NODES DRAINING A SPECIFIC ANATOMIC AREA

The lymph nodes draining the footpad of a mouse were located using the method of the present invention as follows. First, a composition comprising DPPC liposomes containing fluorescein was prepared as disclosed in this disclosure. Next, BALB/c mice weighing 25-50 grams each were anesthetized with tri-bromoethanol and the fur overlying the area of the draining regional lymph nodes was removed with a depilatory. Then, one front footpad was injected with 10 microliters of the composition, for a dose of about 0.45 mg of lipid per mouse, or 9-18 mg/kg body weight of the animal. The animal was illuminated with a fiberoptic tungsten light source (Dolan-Jenner Industries, St. Lawrence, MA US) using a 480 nm excitation interference filter with a 10 nm bandwidth (Edmund Industrial Optics, Barrington, NJ US).

Viewing the ipsilateral forequarter of the animal using normal light did not reveal any portion of the lymphatic system. However, viewing the ipsilateral forequarter of the animal while illuminating the area with a Wood's light with peak excitation at 365 nm caused such intense fluorescence of the lymphatic system that individual lymph nodes draining the footpad were clearly visible through the intact skin of the animal.

Although the present invention has been discussed in considerable detail with reference to certain preferred embodiments, other embodiments are possible. Therefore, the scope of the appended claims should not be limited to the description of preferred embodiments contained in this disclosure.

Claims

WHAT IS CLAIMED IS:
1. A method for locating the lymph nodes draining a specific anatomic area in a human or animal, the method comprising: a) administering to the human or animal one or more than one composition comprising liposomes, where the liposomes comprise one or more than one dye; b) allowing the composition to be taken into the lymph nodes draining the anatomic area, thereby resulting in lymph nodes containing the dye; and c) imaging the dye, thereby locating the lymph nodes.
2. The method of claim 1, further comprising providing the one or more than one composition before administering the composition.
3. The method of claim 1, where the liposomes comprise one or more than one type of lipid selected from the group consisting of 1,2 dipalmitoyl-sn-glycero-3-phosphocholine, phosphatidylcholine, phosphatidylglycerol, phosphatidylethanolamine and cholesterol.
4. The method of claim 1, where the dye is selected from the group consisting of fluorescein, indocyanine green, indigo carmine and eosin yellow.
5. The method of claim 1, where the dye is a fluorescent dye.
6. The method of claim 1, where the composition is administered in a dose of between about 5 mg and about 1000 mg per square meter of body surface area of the human or animal.
7. The method of claim 1, where the composition is administered in a dose of between about 10 mg and about 500 mg per square meter of body surface area of the human or animal.
8. The method of claim 1, where the composition is administered in a dose of about 50 mg per square meter of body surface area of the human or animal.
9. The method of claim 1, where the composition is administered by a route selected from the group consisting of intradermal adniinistration, intramuscular administration, subcutaneous administration, transdermal administration, administration into the breast parenchyma, administration into subserosal surface of the gastrointestinal tract, intraperitoneal administration, intraluminal administration into the gastrointestinal tract and direct administration into the substance of a malignant neoplasm.
10. The method of claim 1, where imaging the dye comprises exciting the dye using electromagnetic radiation.
11. The method of claim 1, where imaging the dye comprises exciting the dye using electromagnetic radiation in the visible spectrum.
12. The method of claim 1, where imaging the dye comprises exciting the dye using electromagnetic radiation in the infrared spectrum.
13. The method of claim 1, where imaging the dye comprises visualization of the dye.
14. The method of claim 1, where imaging the dye comprises visualization of the dye through intact skin.
15. A method for determining the presence or absence of malignant cells in lymph nodes of a patient with a malignancy draining the anatomic area where the malignancy is located, the method comprising: a) selecting a patient with a malignancy having the potential of lymphatic metastases; b) locating the lymph nodes draining the anatomic area where the malignancy is located according to claim 1; c) removing at least part of one or more than one of the lymph nodes located; and d) examining the at least part of one or more than one of the lymph nodes removed histologically for the presence or absence of malignant cells.
16. The method of claim 15, where at least part of one or more than one of the lymph nodes lymph node removed is at least part of a sentinel lymph node.
17. A method for deterrnining the stage of disease in a patient with a malignancy, the method comprising: a) determining the presence or absence of malignant cells in lymph nodes of the patient according to claim 15; and b) referring to staging protocols for the type of malignancy; where the absence of malignant cells in the lymph nodes of the patient indicates a first stage of the malignancy; and where the presence of malignant cells in the lymph nodes of the patient indicates a second stage of the malignancy.
18. A method for treating a patient with a malignancy, the method comprising: a) determining that malignant cells are present in the lymph nodes of the patient according to claim 15; b) taking a therapeutic action based on the presence of malignant cells in the lymph nodes.
19. The method of claim 18, where the therapeutic action is selected from the group consisting of administering a chemotherapeutic agent to the patient, administering heat or cold to the patient, and administering ionizing radiation to the patient.
20. The method of claim 19, where the chemotherapeutic agent is selected from the group consisting of a cytotoxic agent, a hormonal agent and an immunotherapy agent.
21. The method of claim 18, where the therapeutic action is surgical removal of at least part of the regional lymph nodes draining the area of the malignancy.
22. A kit for locating the lymph nodes draining a specific anatomic area in a human or animal, the kit comprising: a) one or more than one container containing a composition comprising liposomes and one or more than one dye; and b) instructions for performing the method of claim 1.
23. The kit of claim 22, further comprising one or more than one instrument for administering the composition to the human or animal.
24. The kit of claim 22, further comprising one or more than one instrument for imaging the dye present in the composition.
25. A kit for locating the lymph nodes draining a specific anatomic area in a human or animal, the kit comprising: a) one or more than one container containing a composition comprising liposomes and one or more than one dye; and b) one or more than one instrument for administering the composition to the human or animal.
26. The kit of claim 25, further comprising instructions for performing a method for locating the lymph nodes draining a specific anatomic area in a human or animal.
27. The kit of claim 25, further comprising one or more than one instrument for imaging the dye present in the composition.
28. A kit for locating the lymph nodes draining a specific anatomic area in a human or animal, the kit comprising: a) one or more than one container containing a composition comprising liposomes and one or more than one dye; and b) one or more than one instrument for imaging the dye present in the composition.
29. The kit of claim 28, further comprising instructions for performing a method for locating the lymph nodes draining a specific anatomic area in a human or animal.
30. The kit of claim 28, further comprising one or more than one instrument for administering the composition to the human or animal.
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US6057105A (en) * 1995-03-17 2000-05-02 Ngi/Cancer Tech Company, Llc Detection of melanoma or breast metastasis with a multiple marker assay
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Cited By (8)

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WO2002100443A2 (en) * 2001-06-11 2002-12-19 Tyco Healthcare Group Lp Identifying tissue within the body using a fluorescent dye
WO2002100443A3 (en) * 2001-06-11 2003-11-20 Tyco Healthcare Identifying tissue within the body using a fluorescent dye
EP1581103A1 (en) * 2002-12-12 2005-10-05 Manoa Medical, Inc. Percutaneous removal of sentinel lymph node using contrast imaging for identification
EP1581103A4 (en) * 2002-12-12 2007-01-31 Manoa Medical Inc Percutaneous removal of sentinel lymph node using contrast imaging for identification
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