# US 12,599,684 B2 · Molecular probes and methods of use

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 12,599,684 B2
- Document ID: US12599684B2
- Status: Granted
- Kind: B2
- Application number: 18/239,441
- Filed: 2023-08-29
- Published: 2024-05-16
- Granted: 2026-04-14
- Earliest claimed: 2014-08-04
- Assignees: Case Western Reserve University
- Applicants: Case Western Reserve University
- Inventors: Zheng-Rong Lu; Zheng Han
- Web page: https://patentgrep.com/patent/US12599684B2

## CPC

- A61K 49/14: Peptides, e.g. proteins
- A61K 49/0032: {Methine dyes, e.g. cyanine dyes}
- A61K 49/0056: {Peptides, proteins, polyamino acids}
- A61K 51/088: {conjugates with carriers being peptides, polyamino acids or proteins (antibodies A61K51/10)}
- 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

A molecular probe includes the following formula: P-L-C wherein P is a EDB-FN targeting peptide, C is a contrast agent; and L is a non-peptide linker that covalently links the peptide to the contrast agent.

## Claims

### Claim 1

A compound selected from the group consisting of the formula:
salts thereof, wherein M is a chelated metal and the dashed lines are optional coordinate covalent bonds, and at least two of the dashed lines form coordinate covalent bonds with the chelated metal.

### Claim 2 (depends on 1)

The compound of claim 1, wherein the chelated metal allows for detection of the compound using magnetic resonance imaging (MRI), positron emission tomography (PET), or single photon emission computed tomography (SPECT).

### Claim 3 (depends on 1)

The compound of claim 1, wherein the chelated metal is selected from Gd+3, Eu+3, Tm+3, Dy+3, Yb+3, Mn+2, Fe+3, 55Co, 64Cu, 67Cu, 47Sc, 66Ga, 68Ga, 90Y, 97Ru, 99mTc, 111In, 109Pd, 153Sm, 177Lu, 186Re, or 188Re.

### Claim 4 (depends on 1)

The compound of claim 1, wherein the chelated metal is selected from Gd3+ or 64Cu.

### Claim 5 (depends on 1)

The compound of claim 1, wherein M is Gd3+.

### Claim 6

A method of detecting the presence, location and/or distribution of cancer cells expressing EDB-FN comprising:
contacting a tissue of a subject with a compound selected from the group consisting of the formula:
salts thereof,
wherein M is a chelated metal and the dashed lines are optional coordinate covalent bonds, and at least two of the dashed lines form coordinate covalent bonds with the chelated metal; and
detecting the compound in the tissue of the subject bound to EDB-FN using an imaging modality, wherein the detected presence, location and/or distribution of the compound bound to EDB-FN in the tissue is correlated with the presence, location and/or distribution of EDB-FN expressing cancer cells in the tissue.

### Claim 7 (depends on 6)

The method of claim 6, wherein the contacting step is in vivo, ex vivo, or in vitro.

### Claim 8 (depends on 6)

The method of claim 6, wherein the compound is systemically administered to a subject having or suspected of having cancer.

### Claim 9 (depends on 8)

The method of claim 8, wherein the cancer is selected from breast cancer, liver cancer, stomach cancer, colon cancer, pancreatic cancer, ovarian cancer, lung cancer, kidney cancer, prostate cancer, testicular cancer, glioblastoma, sarcoma, bone cancer, brain cancer, head and neck cancers, or skin cancer.

### Claim 10 (depends on 6)

The method of claim 6, wherein the subject is administered the compound to determine cancer aggressiveness, and wherein a greater amount of detected and/or distributed compound bound to EDB-FN compared to a control is indicative of an increase in cancer aggressiveness.

### Claim 11 (depends on 6)

The method of claim 6, wherein the compound is detected using magnetic resonance imaging (MRI), positron emission tomography (PET), or single photon emission computed tomography (SPECT).

### Claim 12 (depends on 6)

The method of claim 6, wherein the chelated metal is selected from Gd+3, Eu+3, Tm+3, Dy+3, Yb+3, Mn+2, Fe+3, 55Co, 64Cu, 67Cu, 47Sc, 66Ga, 68Ga, 90Y, 97Ru, 99mTc, 111In, 109Pd, 153Sm, 177Lu, 186Re, or 188Re.

### Claim 13 (depends on 6)

The method of claim 6, wherein chelated metal is selected from Gd3+ or 64Cu.

### Claim 14 (depends on 6)

The method of claim 6, wherein the chelated metal is Gd3+.