Methods and chemical preparations for time-limited marking of biopsy sites

• US 6,161,034 A
• Filed: 02/02/1999
• Issued: 12/12/2000
• Est. Priority Date: 02/02/1999
• Status: Expired due to Term

• Current Assignee: Senorx Incorporated (Becton, Dickinson & Co)
• Original Assignee: Senorx Incorporated (Becton, Dickinson & Co)
• Inventors: Jones, Michael L., Burbank, Fred H., Lubock, Paul, Forcier, Nancy
• Primary Examiner(s): PELHAM, JOSEPH MOORE
• Application Number:
  US09/241,936
• Time in Patent Office: 679 Days
• Field of Search: 600/431, 600/414, 600/420, 600/426, 600/458, 424/9.1, 128/898, 128/899
• US Class Current: 600/431
• CPC Class Codes: A61B 10/02 Instruments for taking cell samples or for biopsy A61B10/0038 and A61B10/0045 take precedence; needle locating or guiding means A61B17/3403; samplers for enzymology or microbiology C12M1/26; sampling or preparing biological specimens G01N33/48
• CPC Class Codes: A61B 2017/00004 (bio)absorbable, (bio)resorbable, resorptive for implantable prostheses A61F2210/0004
• CPC Class Codes: A61B 2090/3788 transmitter only
• CPC Class Codes: A61B 2090/3908 Soft tissue, e.g. breast tissue
• CPC Class Codes: A61B 2090/3925 ultrasonic
• CPC Class Codes: A61B 2090/3929 Active markers
• CPC Class Codes: A61B 2090/3933 Liquid markers
• CPC Class Codes: A61B 2090/395 with marking agent for marking skin or other tissue
• CPC Class Codes: A61B 2090/3975 active
• CPC Class Codes: A61B 2090/3987 Applicators for implanting markers
• CPC Class Codes: A61B 2090/3995 Multi-modality markers
• CPC Class Codes: A61B 90/39 Markers, e.g. radio-opaque or breast lesions markers
• CPC Class Codes: A61K 49/006 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 Class Codes: A61M 37/0069 Devices for implanting pellets, e.g. markers or solid medicaments for introducing of radioactive sources for interstitial radiation therapy, i.e. brachytherapy A61N5/1027

Abstract

Detectable markers that may be introduced into a cavity created by removal of a biopsy specimen to mark the location of the biopsy site so that it may be located in a subsequent medical/surgical procedure. The markers remain present in sufficient quantity to permit detection and location of the biopsy site at a first time point (e.g., 2 weeks) after introduction but clear from the biopsy site or otherwise not interfere with imaging of tissues adjacent the biopsy site at a second time point (e.g., 5-7 months) after introduction.

Claims

1. A method for marking a site within the body of a mammalian patient from which a tissue sample has been removed, said method comprising the step of:

A. introducing into the site a detectable marker that (i) remains present at the site in sufficient quantity to permit detection and location of the site for at least a predetermined first time period after introduction and (ii) does not interfere with imaging of tissue adjacent the site at a predetermined second time point after introduction.

2. The method of claim 1 wherein the detectable marker is imageable, and wherein the marker remains present at the site in sufficient quantity to allow detection of the site by imaging of the marker at said first time point but clears sufficiently from the site so as to not interfere with imaging of tissue adjacent the site at said second time point.

3. The method of claim 2 wherein the imaging method by which the detectable marker is selected from the group of imaging methods consisting of:

X-ray;

fluoroscopy;

mammography;

computed tomography;

magnetic resonance imaging;

ultrasound;

Doppler,

radiation detector; and

,

possible combinations thereof.

4. The method of claim 1 wherein the marker is detectable by palpation.

5. The method of claim 4 wherein the palpable marker is selected from the group consisting of:

at least one balloon;

at least one bead;

a flowable space occupying material;

a collagenous material,

a gelatinous material;

gelatin;

cross-linked gelatin; and

,

possible combinations thereof.

6. The method of claim 1 wherein the marker is visually detectable.

7. The method of claim 6 wherein the visually detectable marker is a colored substance selected from the group consisting of:

a dye;

a colorant;

colorant particles;

carbon; and

,

possible combinations thereof.

8. The method of claim 1 wherein the detectable marker is detectable by a detection method selected from the group consisting of:

imaging of the marker;

palpation of the marker;

visualization of the marker; and

,

possible combinations thereof.

9. The method of claim 1 wherein the detectable marker introduced in Step A comprises:

a detectable material that will interfere with imaging of tissues adjacent thereto and which remains present at the site in sufficient quantity to permit location of the site by imaging until the first time point but clears sufficiently from the site to not interfere with imaging of tissue adjacent the site at said second time point.

10. The method of claim 1 wherein the detectable marker introduced in Step A comprises:

a quantity of detectable material that, if introduced into the site alone, would clear from the site such that a detectable quantity of the marker would no longer be present at the site at 2 weeks after introduction of said detectable marker; and

,

a clearance delaying element that delays the clearance of said material from the site such that (i) a detectable quantity of said material remains present at the site until at least said first time point and (ii) said material clears sufficiently from the site to permit imaging of tissue adjacent to the site without interference from said detectable marker at said second time point.

11. The method of claim 9 wherein the detectable material is a chemical compound that has a solubility constant of less than 1×

10^-3 grams per 100 cubic centimeters of water.

12. The method of claim 11 wherein said chemical compound is selected from the group consisting of:

AgCl;

Agl;

BaCO₃ ;

BaSO₄ ;

K;

CaCO₃ ;

ZnO;

Al₂ O₃ ; and

,

the possible combinations thereof.

13. The method of claim 10 wherein the detectable material is selected from the group consisting of:

AGNO₃ ;

ammonium salts;

sodium salts;

potassium salts;

ethiodized oil;

isohexol;

isopamidol;

gas;

lipid;

oil; and

,

the possible combinations thereof.

14. The method of claim 10 wherein the clearance delaying element is selected from the group consisting of:

polylactic acid;

polyglycolic acid;

polycapriolactone;

an encapsulating material;

collagen

renatured collagen;

gelatin;

renatured gelatin;

crosslinked gelatin;

a balloon;

a microsphere; and

the possible combinations thereof.

15. The method of claim 1 wherein the detectable marker comprises a material that is detectable by radiographic imaging means.

16. The method of claim 1 wherein the detectable marker comprises a material that is detectable by sonographic imaging means.

17. The method of claim 1 wherein the detectable marker comprises a material that is detectable by magnetic imaging means.

18. The method of claim 1 wherein the detectable marker comprises a dry powder.

19. The method of claim 1 wherein the detectable marker comprises a sponge.

20. The method of claim 1 wherein the detectable marker comprises a suspension.

21. The method of claim 1 wherein the detectable marker comprises a slurry.

22. The method of claim 1 wherein the detectable marker comprises a collagenous material having radiographically imageable matter attached thereto.

23. The method of claim 22 wherein the collagenous material of the marker comprises renatured collagen.

24. The method of claim 23 wherein the collagenous material is also covalently crosslinked.

25. The method of claim 22 wherein the radiographically imageable matter comprises metal ions.

26. The method of claim 22 wherein the radiographically imageable matter comprises a gas.

27. The method of claim 22 wherein the collagenous material of the marker comprises renatured collagen and the radiographically imageable matter of the marker comprises metal ions that are bound to said renatured collagen.

28. The method of claim 25 wherein the metal ions are silver ions.

29. A method according to claim 28 wherein the marker is prepared by a process that comprises:

a. obtaining a quantity of denatured collagenous material;

b. renaturing the collagenous material; and

,

c. binding metal ions to the renatured collagenous material.

30. A method according to claim 26 wherein the marker is prepared by a process that comprises:

a. obtaining a quantity of denatured collagenous material;

b. renaturing the collagenous material; and

,

c. dispersing a gas throughout the renatured collagenous material.

31. The method of claim 22 wherein the decectable marker comprises a gelatinous material having radiographically imageable matter combined therewith.

32. The method of claim 31 wherein the gelatinous material of the marker comprises renatured gelatin.

33. The method of claim 32 wherein the gelatinous material is also covalently crosslinked.

34. The method of claim 31 wherein the radiographically imageable matter comprises metal ions.

35. The method of claim 31 wherein the radiographically imageable matter comprises a gas.

36. The method of claim 31 wherein the gelatinous material of the marker comprises renatured gelatin and the radiographically imageable matter of the marker comprises metal ions that are bound to said renatured gelatin.

37. The method of claim 34 wherein the metal ions are silver ions.

38. The method of claim 29 wherein the marker is prepared by a process that comprises:

d. obtaining a quantity of denatured gelatin;

e. renaturing the gelatin; and

,

f. binding metal ions to the renatured gelatin.

39. The method of claim 30 wherein the marker is prepared by a process that comprises:

d. obtaining a quantity of denatured gelatin;

e. renaturing the gelatin; and

,

f. dispersing gas throughout the renatured gelatin.

40. A method of identifying tissue that is located within a predetermined distance of a boundary of a biopsy cavity that has been created by the removal of a biopsy specimen from a patient, said method comprising the steps of:

a. introducing into the biopsy cavity a quantity of marker material that is visibly distinguishable from blood and surrounding tissue so as to delineate the outer boundaries of the biopsy cavity;

b. forming an incision in the patient to permit visualization of the marker material and the boundaries of the biopsy cavity delineated thereby; and

,

c. identifying the tissue that lies within said predetermined distance of the boundary of the biopsy cavity.

41. The method of claim 40 wherein it is desired to remove the tissue that lies within said predetermined distance of a boundary of the biopsy cavity and wherein the method further comprises the step of:

d) excising and removing tissue that lies within said predetermined distance of the boundary of the biopsy cavity.