# US 11,077,212 B2 · Molecular imaging of cancer cells in vivo

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- Number: US 11,077,212 B2
- Document ID: US11077212B2
- Status: Granted
- Kind: B2
- Application number: 13/813,605
- Filed: 2011-08-24
- Published: 2013-05-23
- Granted: 2021-08-03
- Earliest claimed: 2010-08-24
- Assignees: H. Lee Moffitt Cancer Center and Research Institute, Inc.
- Applicants: David L. Morse; Robert J. Gillies; William Bradford Carter; Narges K. Tafreshi; Marilyn M. Bui; Steven A. Enkemann
- Inventors: David L. Morse; Robert J. Gillies; William Bradford Carter; Narges K. Tafreshi; Marilyn M. Bui; Steven A. Enkemann
- Web page: https://patentgrep.com/patent/US11077212B2

## CPC

- A61K 49/0058: {Antibodies}
- A61K 49/0002: {General or multifunctional contrast agents, e.g. chelated agents}
- A61K 51/1045: {against animal or human tumor cells or tumor cell determinants}
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

Cellular targets on cancer cells have been identified that can be used with targeted molecular imaging to detect the cancer cells in vivo. Non-invasive methods for detecting cancer cells, such as metastasized cancer cells, are therefore provided. Also provided are compositions and kits for use in the disclosed methods.

## Claims

### Claim 1

A non-invasive method for in vivo detection of metastasized breast cancer cells in a subject, the method comprising the steps of:
(a) administering to the subject a first targeted imaging probe and a second targeted imaging probe,
wherein the targeted imaging probes each comprise an antibody linked to a NIR fluorophore, wherein the antibody of the first imaging probe specifically binds carbonic anhydrase 9 (CAIX), wherein the antibody of the second imaging probe specifically binds carbonic anhydrase 12 (CAXII); and
(b) imaging the subject with a molecular imaging device to detect the targeted imaging probes in the subject, wherein detection of the targeted imaging probes in an organ or a tissue of the subject is an indication of metastasized breast cancer cells in the organ or the tissue.

### Claim 2 (depends on 1)

The method of claim 1, wherein the antibody that specifically binds CAIX is monoclonal antibody clone 303123 and the antibody that specifically binds CAXII is monoclonal antibody clone 315602.

### Claim 3

A non-invasive method for intraoperative detection of metastasized breast cancer cells in a subject, the method comprising the steps of:
(a) administering to the subject a first targeted imaging probe and a second targeted imaging probe,
wherein the targeted imaging probes each comprise an antibody linked to a near-infrared (NIR) fluorophore, and
wherein the antibody of the first targeted imaging probe specifically binds carbonic anhydrase 9 (CAIX),
wherein the antibody of the second targeted imaging probe specifically binds carbonic anhydrase 12 (CAXII); and
(b) imaging the subject with a molecular imaging device to detect the targeted imaging probes in the subject,
wherein detection of the targeted imaging probes in an organ or a tissue of the subject is an indication of metastasized breast cancer cells in the organ or the tissue.

### Claim 4 (depends on 3)

The method of claim 3, wherein the antibody that specifically binds CAIX is monoclonal antibody clone 303123.

### Claim 5 (depends on 3)

The method of claim 3, wherein the antibody that specifically binds CAXII is monoclonal antibody clone 315602.

### Claim 6 (depends on 3)

The method of claim 3, wherein the antibody that specifically binds CAIX is monoclonal antibody clone 303123, and wherein the antibody that specifically binds CAXII is monoclonal antibody clone 315602.

### Claim 7 (depends on 3)

The method of claim 3 further comprising removing the metastasized breast cancer cells identified via the imaging from the organ or the tissue of the subject.

### Claim 8 (depends on 3)

The method of claim 3 further comprising treating the subject for cancer if the imaging indicates the presence of metastasized breast cancer cells.

### Claim 9 (depends on 1, 8)

The method of claim 8 further comprising repeating the steps of claim 1 following treatment.

### Claim 10 (depends on 3)

The method of claim 3, wherein the metastasized breast cancer cells are breast cancer cells metastasized to one or more lymph nodes.

### Claim 11 (depends on 10)

The method of claim 10, wherein the one or more lymph nodes are axillary lymph node and/or sentinel lymph nodes.