# US 10,870,664 B2 · Nitrogen-containing macrocyclic conjugates as radiopharmaceuticals

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- Number: US 10,870,664 B2
- Document ID: US10870664B2
- Status: Granted
- Kind: B2
- Application number: 16/378,716
- Filed: 2019-04-09
- Published: 2019-07-25
- Granted: 2020-12-22
- Earliest claimed: 2008-12-02
- Assignees: The University of Melbourne
- Applicants: The University of Melbourne
- Inventors: Paul Stephen Donnelly; Michelle Therese Ma; Denis Bernard Scanlon
- Web page: https://patentgrep.com/patent/US10870664B2

## CPC

- C07D 521/00: Heterocyclic compounds containing unspecified hetero rings
- A61K 51/0482: {chelates from cyclic ligands, e.g. DOTA}
- A61K 51/082: {the peptide being a RGD-containing peptide}
- A61K 51/088: {conjugates with carriers being peptides, polyamino acids or proteins (antibodies A61K51/10)}
- A61P 35/00: Antineoplastic agents
- A61K 49/06: Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K 49/08: characterised by the carrier
- A61K 49/10: Organic compounds
- A61K 49/101: {the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals}
- A61K 51/00: Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K 51/02: characterised by the carrier {, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus}
- A61K 51/04: Organic compounds
- A61K 51/08: Peptides, e.g. proteins {, carriers being peptides, polyamino acids, proteins}
- A61K 51/10: Antibodies or immunoglobulins; Fragments thereof {, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody}
- A61K 51/106: {the tumor cell being from kidney or bladder}
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention relates to compounds that are useful as metal ligands and which either contain a molecular recognition moiety or can be bound to a molecular recognition moiety and methods of making these compounds. Once the compounds that contain a molecular recognition moiety are coordinated with a suitable metallic radionuclide, the coordinated compounds are useful as radiopharmaceuticals in the areas of radiotherapy and diagnostic imaging. The invention therefore also relates to methods of diagnosis and therapy utilising the radiolabelled compounds of the invention.

## Claims

### Claim 1

A method of treating cancer in a subject, the method including the step of administering to a subject in need thereof, a therapeutically effective amount of a compound of Formula (I):
wherein L is a nitrogen-containing macrocyclic cage metal ligand of the formula:
wherein V is CR4;
R4 is CH3;
X is a group of the formula —(CH2)n—;
n is selected from 2, 3 and 4; and
Y is a molecular recognition moiety, which is bound to the remainder of the molecule by a spacer moiety,
or a pharmaceutically acceptable salt thereof;
wherein the compound of formula (I) is complexed with a radionuclide, wherein the radionuclide is of a metal selected from the group consisting of Cu, Tc, Gd, Ga, In, Co, Re, Fe, Au, Ag, Rh, Pt, Bi, Cr, W, Ni, V, Ir, Zn, Cd, Mn, Ru, Pd, Hg and Ti.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the cancer is breast cancer, colon cancer, lung cancer, ovarian cancer, prostate cancer, head and/or neck cancer, renal cancer, gastric cancer, pancreatic cancer or brain cancer.

### Claim 3 (depends on 2)

The method according to claim 2, wherein the cancer is prostate cancer.

### Claim 4 (depends on 1)

A method of treating or detecting a hyperproliferative disease, the method including the step of administering to a subject in need thereof, a therapeutically effective amount of the compound of Formula (I) as defined in claim 1.

### Claim 5 (depends on 4)

The method according to claim 4, wherein the hyperproliferative disease is a leukemia, psoriasis or restenosis.

### Claim 6 (depends on 1)

A method of treating or detecting a pre-cancer condition, the method including the step of administering to a subject in need thereof, a therapeutically effective amount of the compound of Formula (I) as defined in claim 1.

### Claim 7 (depends on 6)

The method according to claim 6, wherein the pre-cancer condition is familial adenomatous polyposis, colonic adenomatous polyps, myeloid dysplasia, endometrial dysplasia, endometrial hyperplasia with atypia, cervical dysplasia, vaginal intraepithelial neoplasia, benign prostatic hyperplasia, papillomas of the larynx, actinic and solar keratosis, seborrheic keratosis or keratoacanthoma.

### Claim 8 (depends on 1)

The method according to claim 1, wherein the radionuclide is Cu.

### Claim 9 (depends on 8)

The method according to claim 8, wherein the radionuclide is selected from the group consisting of 60Cu, 62Cu, 64Cu, and 67Cu.