Labeling composition for cancer lesion

Patent metadata

Field	Value
Publication number	US-10166302-B2
Application number	US-201314758179-A
Country	US
Kind code	B2
Filing date	Dec 4, 2013
Priority date	Dec 26, 2012
Publication date	Jan 1, 2019
Grant date	Jan 1, 2019

Abstract

The present invention relates to a labeling composition for a cancer lesion, having a complex in which a pigment for straining living tissues, a radioactive isotope, or a combination thereof binds to macro aggregated albumin (MAA). A method for providing information regarding a cancer lesion site using the labeling composition for a cancer lesion. A labeling kit for a cancer lesion having the labeling composition for a cancer lesion; and a complex in which a pigment for straining living tissues binds to MAA included in the labeling composition for a cancer lesion. The labeling composition for a cancer lesion according to the present invention binds to a cancer lesion to detect a site, size, and the like of the cancer lesion in real time, thereby improving the success rate of a surgical operation for the cancer lesion and also preventing excessive loss of normal tissues.

First claim

The invention claimed is:

1. A method for providing information about a size and a site of a cancer lesion, the method comprising:
(a) adding a radioactive isotope to a thiol macroaggregated albumin (MAA) to obtain a complex in which the thiol MAA binds to the radioactive isotope;
(b) adding at least one pigment for staining living tissues to the complex in (a);
(c) mixing the complex in (b) with a first mixture comprising thrombine and aprotinin and a second mixture comprising fibrinogen and CaCl 2 to obtain the complex entangled in a fibrin;
(d) administering directly to a cancer tissue to be removed in a subject the complex obtained from (c); and
(e) identifying a size and a site of the cancer lesion through a signal selected from the group consisting of a color, a near-infrared fluorescence, a radioactivity, and a combination of two or more thereof, from the cancer tissue in real time during cancer-removing surgery.

2. The method of claim 1 , wherein the pigment for staining living tissues is a visible pigment, or a fluorescent pigment.

3. The method of claim 2 , wherein the visible pigment is selected from the group consisting of natural red, nile blue, bismark brown, lithium carmine, trypan blue, j anus green, methyl violet, o-lamine, malachite green, safranine, eosin, congo red, erythrocin, nigrosin, alcian blue hematoxylin, aniline blue, light green and a combination of two or more thereof.

4. The method of claim 2 , wherein the fluorescent pigment is a near-infrared fluorescent pigment.

5. The method claim 4 , wherein the near-infrared fluorescent pigment is an indocyanine green (ICG).

6. The method of claim 1 , wherein the radioactive isotope is selected from the group consisting of H-3, C-14, P-32, S-35, Cl-36, Cr-51, Co-57, Co-58, Cu-64, Fe-59, Y-90, I-124, I-125, Re-186, I-131, Tc-99m, Mo-99, P-32, CR-51, Ca-45, Ca-68, and a combination of two or more thereof.

7. The method of claim 1 , wherein the complex is captured inside of a gelatin or a gelatin sponge.

8. The method of claim 7 , wherein the gelatin sponge is a construct in which an isopeptide bond is produced between an amine group of a side chain of lysine and a carboxylic group of a side chain of glutamate or aspartate present in the gelatin.

9. The method of claim 1 , wherein the cancer is a solid cancer.

10. The method of claim 9 , wherein the solid cancer is selected from the group consisting of prostate cancer, breast cancer, uterus cancer, skin cancer, cervical cancer, lung cancer, brain tumor, gastrointestinal tumor, liver cancer, soft tissue sarcoma, lymphoma, and a combination of two or more thereof.

11. A method for providing information about a size and a site of a cancer lesion, the method comprising:
(a) adding at least one pigment for staining living tissues to a thiol macroaggregated albumin (MAA) to obtain a complex in which the thiol MAA binds to the pigment for staining living tissues;
(b) mixing the complex in (a) with a first mixture comprising thrombine and aprotinin and a second mixture comprising fibrinogen and CaCl 2 to obtain the complex entangled in a fibrin;
(c) mixing the complex in (b) with a gold leaf coil to which a radioactive isotope is bound;
(d) adding a gelatin to the mixture in (c) and then heating the resultant mixture to obtain a solid type labeling agent in which the mixture in (c) encaptured in a gelatin sponge;
(e) administering directly to a cancer tissue to be removed in a subject the solid type labeling agent obtained from (d); and
(f) identifying the size and the site of the cancer lesion through a signal selected from the group consisting of a color, a near-infrared fluorescence, a radioactivity, and a combination of two or more thereof, from the cancer tissue in real time during cancer-removing surgery.

12. A kit for surgical removal of a cancer lesion comprising a labeling composition comprising a complex in which a macroaggregated albumin (MAA) is bound to a pigment for staining living tissues and a radioactive isotope, wherein the MAA is further bound to a fibrin, wherein the labeling composition is capable of being administered to a cancer tissue and the composition is capable of being used to identify a site and a size of a cancer lesion in real time during cancer-removing surgery.

13. A kit for surgical removal of a cancer lesion comprising a labeling composition comprising a complex in which a macroaggregated albumin (MAA) is bound to a pigment for staining living tissues and a radioactive isotope, wherein the MAA is further bound to a fibrin, wherein the labeling composition is capable of being administered to a cancer tissue and the composition is capable of being used to identify a site and a size of a cancer lesion in real time during cancer-removing surgery, and wherein the pigment for staining living tissues is a visible pigment, or a fluorescent pigment.

Assignees

• Nat Cancer Ct

Inventors

• Kim Seok Ki
• Kang Se Hun
• Kim Seok Won
• Jung So Youn

Classifications

• G01N33/575 Primary

  for cancer · CPC title

• G01N2333/765

  Serum albumin, e.g. HSA · CPC title

• G01N33/58 Primary

  involving labelled substances (G01N33/53 takes precedence) · CPC title

• A61K51/081 Primary

  the protein being an albumin, e.g. human serum albumin [HSA], bovine serum albumin [BSA], ovalbumin · CPC title

• A61K49/006

  Biological staining of tissues in vivo, e.g. methylene blue or toluidine blue O administered in the buccal area to detect epithelial cancer cells, dyes used for delineating tissues during surgery · CPC title