Drug – bio-affecting and body treating compositions – Radionuclide or intended radionuclide containing; adjuvant... – In an organic compound
Reexamination Certificate
2000-05-30
2002-10-01
Hartley, Michael G. (Department: 1616)
Drug, bio-affecting and body treating compositions
Radionuclide or intended radionuclide containing; adjuvant...
In an organic compound
C424S009100, C424S009610
Reexamination Certificate
active
06458336
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to a substance and method for identifying the sentinel lymph node in patients, particularly those with cancer. More particularly, the present invention relates to a detectably labeled porphyrin compound for identifying the sentinel lymph node.
BACKGROUND OF THE INVENTION
One of the major techniques for determining the prognosis of cancer, particularly breast cancer, involves examining the lymph nodes of the axilla or armpit of the patient. It is well known that a major aspect in assessing the stage of the cancer revolves around whether the cancer has spread to the lymph nodes. It is therefore important to have an effective technique for identifying the spread of the cancer through the lymphatic system.
In the lymphatic system of the human body, lymphatic fluid flows from the breast through the lymph channels and is filtered through the lymph nodes. The first stop is the “first lymph node” or the “sentinel lymph node.” If the cancer has spread to the lymph nodes, the sentinel lymph node should be positive (i.e., cancerous). If the first lymph node is negative, it can be assumed that the rest of the lymph nodes are negative. Therefore, it is crucial that this first lymph node or sentinel lymph node be accurately identified.
A known technique for identifying the sentinel lymph node(s) involves the use of two substances: a blue substance and a radioactive substance. However, the sentinel lymph node may not be blue, or may not be radioactive, using this technique. This causes problems relating to the accuracy of the identification. Therefore, there is a need for an improved and more accurate technique for the identification of the sentinel lymph node.
In more detail, the known technique involves the two substances lymphazurin blue and sulfur colloid. There is a disadvantage to lymphazurin blue in that it cannot be radio-labeled. Another problem is that not only does the procedure require two substances, it also requires two separate injections. Therefore, there is a need for an improved and simplified technique for the identification of the sentinel lymph node.
Giuliano et al. describe the feasibility and accuracy of lymphatic mapping with sentinel lymphadenectomy in patients with breast cancer. (1) The conclusion was that lymphatic mapping can accurately identify the sentinel node in most patients.
Krag et al. describe the surgical resection and radiolocalization of the sentinel lymph node in breast cancer using a gamma probe. (2) It was concluded that radiolocalization and selective resection of sentinel lymph nodes is possible, and that the sentinel lymph node appears to predict correctly the status of the remaining axilla.
Wong describes a chemical method for labeling a hematoporphyrin derivative (HPD) with Technetium-99m. (3)
Rousseau et al. describe the synthesis, tissue distribution, and tumor uptake of
99
Tc-labeled-tetrasulfophtalocyanine [
99
Tc] TSPC, which was prepared by condensing sulfophthalic acid and pertechnetate in the presence of a reducing agent. (4) Reaction products were purified in various chromatographic systems and were characterized by combustion, specific activity, and spectral analyses.
99
Tc emits &bgr; radiation. TSPC is a tetrasulfonic acid derivative within a general class of compound known as phthalocyanines. Phthalocyanines are not naturally occurring substances, but they have been reported to mimic the activities of naturally occurring porphyrins. The tissue distribution pattern of the product was studied in rats bearing tumors. Most of the [
99
Tc] TSPC accumulated in the liver, kidneys, ovaries, and uterus, whereas tumor uptake occurred mainly in the exterior cell layers. The in vivo stability of the complex was evidenced by the absence of
99
Tc accumulation in the thyroid and the stomach.
Weber et al. describe magnetic properties of transition metal derivatives of 4′, 4″, 4′″- Tetrasulfophthalocyanine. (5) The tetrasulfophthalocyanine complexes of manganese, iron, cobalt, nickel, and copper were prepared in high purity and the magnetic moments of these substances were determined both in the solid state and in solution.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide an improved technique for the identification of the sentinel lymph node that is more accurate than known techniques.
It is also an object of the present invention to provide an improved technique for the identification of the sentinel lymph node that simplifies the identification procedure over known techniques.
The present invention accomplishes the above objectives and more by providing in one embodiment a radioactive or radio-labeled blue porphyrin for identifying the sentinel lymph node or nodes. In the embodiment, a blue porphyrin is labeled with Technetium-99m, (Tc99m), which emits &ggr; radiation. The radio-labeled blue porphyrin is injected into tissue surrounding a tumor lesion of a subject or into tissue surrounding the biopsy cavity in cases where the tumor has been previously excised. The injection of the radioactive chemical compound thereby stains the lymphatic channels to help identify that particular first node or sentinel node draining the area by using the bluish color as well as a Geiger counter. The technique of the present invention is for use in a sentinel lymph node biopsy in breast cancer or any other cancer or situation where the sentinel lymph node needs to be identified.
The advantage of the present invention is that it combines in one compound and one injection the procedure that previously required two different compounds and two separate injections. The present invention in one embodiment therefore comprises a single purified porphyrin, rather than a mixture of porphyrins as in the known art. And, the present invention uses sodium salt instead of the ammonium salt of the known art.
The present invention in another embodiment comprises a non-radioactive metal (manganese in a preferred embodiment) attached to the porphyrin compound for identification of the sentinel lymph node using a Magnetic Resonance Imaging (MRI) examination.
In summary, the present invention in one embodiment provides a detectably labeled porphyrin compound.
The present invention in another embodiment provides a method of producing the detectably labeled porphyrin compound, comprising the steps of: preparing a stannous chloride solution; adding Tc-99m-sodium pertechnetate solution into the stannous chloride solution to create a mixture; stirring the mixture at room temperature; adding purified phthalocyanine tetrasulfonate (PCTS) to the mixture; stirring the mixture again at room temperature; incubating the mixture at room temperature; and passing the mixture through a filter.
The present invention in another embodiment provides a method of identifying a sentinel lymph node, comprising the steps of: injecting the detectably labeled porphyrin compound into a tumor, wherein the porphyrin compound is detectably labeled with a radiolabel which is a &ggr;-emitting radioactive metal; and detecting radioactive emission or a color so as to detect and thereby identify the sentinel lymph node.
The present invention in another embodiment provides a method of identifying a sentinel lymph node, comprising the steps of: injecting the detectably labeled porphyrin compound into tissue surrounding a tumor, wherein the porphyrin compound is detectably labeled with a non-radioactive metal; and taking a series of magnetic resonance images to identify the sentinel lymph node by viewing the images showing the injected detectably labeled porphyrin compound.
DETAILED DESCRIPTION OF THE INVENTION
As used in this application, a “porphyrin compound” means and includes any porphyrin, porphyrin analog or homolog, or derivative of a porphyrin or porphyrin analog or homolog. In a presently preferred embodiment the porphyrin compound is a blue porphrin such as phthalocyanine tetrasulfonate. The porphyrin compound could also be phthalocyanine, hematoporphyrin, metalloporphyrin, or metall
Chaglassian Ted
El-Tamer Mahmoud
Fawaz Rashid
Saouaf Rola
Wang Theodore
Cooper & Dunham LLP
Hartley Michael G.
The Trustees of Columbia University in the City of New York
White John P.
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