# US 2024/0189460 A1 · High purity copper radiopharmaceutical compositions and diagnostic and therapeutic uses thereof

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- Number: US 2024/0189460 A1
- Document ID: US20240189460A1
- Status: Published application
- Kind: A1
- Application number: 18/474,218
- Filed: 2023-09-25
- Published: 2024-06-13
- Earliest claimed: 2022-09-23
- Assignees: Nuclidium AG; University of Basel
- Applicants: Nuclidium AG; University of Basel
- Inventors: Leila JAAFAR-THIEL; Melpomeni FANI; Jacopo MILLUL; Francesco DE ROSE
- Web page: https://patentgrep.com/patent/US20240189460A1

## CPC

- A61K 51/0482: {chelates from cyclic ligands, e.g. DOTA}
- A61B 5/055: involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
- A61K 31/30: Copper compounds
- A61K 51/0455: {having six-membered rings with one nitrogen as the only ring hetero atom}
- A61K 51/0459: {having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine}
- A61K 51/083: {the peptide being octreotide or a somatostatin-receptor-binding peptide}
- A61K 51/088: {conjugates with carriers being peptides, polyamino acids or proteins (antibodies A61K51/10)}
- A61P 35/00: Antineoplastic agents
- C07B 59/002: {Heterocyclic compounds}
- C07B 59/004: {Acyclic, carbocyclic or heterocyclic compounds containing elements other than carbon, hydrogen, halogen, oxygen, nitrogen, sulfur, selenium or tellurium}
- A61K 2121/00: Preparations for use in therapy
- A61K 2123/00: Preparations for testing in vivo
- C07B 2200/05: Isotopically modified compounds, e.g. labelled
- 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)
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)

## Abstract

The present disclosure relates to the field of nuclear imaging and therapy, and more specifically to high purity copper radiotracer compositions useful in imaging, such as positron emission tomography (PET) and single-photon emission computerized tomography (SPECT), and therapy. More specifically, the present disclosure relates to novel compositions useful in imaging and treatment of conditions such as prostate cancer, somatostatin receptor-expressing tumors, like neuroendocrine tumor, epithelial tumors, as well as to methods wherein such compositions are prepared.

## Claims

### Claim 1

A composition comprising a radiotracer, the radiotracer comprising:
a chelating moiety;
a copper radionuclide (*Cu) chelated by the chelating moiety; and
a targeting moiety covalently linked to the chelating moiety;
wherein the composition is characterized by one or more of:
molar activity of ≥3 MBq/nmol;
radiochemical purity of ≥91%;
activity concentration of ≥8 MBq/mL; and
radionuclidic purity of the radiotracer of ≥95% at the end of synthesis.

### Claim 2 (depends on 1)

The composition according to claim 1, wherein the radiotracer is of Formula X*:
or is a pharmaceutically acceptable salt thereof,
wherein:
is the chelating moiety;
*Cu is 61Cu, 62Cu, 64Cu, or 67Cu;
L is a bond or a linker moiety;
V is the targeting moiety;
n is an integer from 1 to 10;
m is an integer from 1 to 10; and
p is an integer from 1 to 10.

### Claim at position 3

3-12. (canceled)

### Claim 13 (depends on 2)

The composition according to claim 2, wherein
is according to Formula II or II′:
wherein:
X1, X2, and X3 are individually selected from —OH, —NH2, and —SH, including deprotonated variants thereof depending on chelation with *Cu;
any methylene is optionally substituted with oxo, thiol, or hydroxyl; and
denotes the point of attachment to the linker moiety (when L is a linker moiety) or to the targeting moiety (when L is a bond).

### Claim 14

(canceled)

### Claim 15 (depends on 13)

The composition according to claim 13, wherein
is selected from Formula III, II′i, IIii, and IIiii:

### Claim at position 7

16-17. (canceled)

### Claim 18 (depends on 15)

The composition according to claim 15, wherein the chelating moiety comprises: 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA); 2,2′-(7-(I-carboxy-4-oxopentyl)-1,4,7-triazonane-1,4-diyl)diacetic acid (NODAGA); 2-(4,7-bis(carboxymethyl)-1,4,7-triazonan-1-yl)succinic acid (NODASA); (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) (DOTA); (1,4,7,10-tetraazacyclododecane, 1-(glutaric acid)-4,7,10-triacetic acid) (DOTAGA); or (1,4,7,10-tetraazacyclododecane, 1-(succinic acid)-4,7,10-triacetic acid) (DOTASA).

### Claim 19 (depends on 18)

The composition according to claim 18, wherein the chelating moiety comprises NOTA, NODASA, or NODAGA.

### Claim 20 (depends on 19)

The composition according to claim 19, wherein the chelating moiety comprises NODAGA.

### Claim 21 (depends on 18)

The composition according to claim 18, wherein *Cu is 61Cu or 67Cu.

### Claim at position 12

22-23. (canceled)

### Claim 24 (depends on 21)

The composition according to claim 21, wherein the targeting moiety is recognized by a molecular target expressed by malignant or premalignant cells, cells in a tumor microenvironment, inflammatory tissues, or sites of tissue remodeling at sites of a myocardial infarct or fibrosis in interstitial lung disease.

### Claim 25 (depends on 24)

The composition according to claim 24, wherein the molecular target is a tumor-specific antigen (TSA) or tumor-associated antigen (TAA).

### Claim 26

(canceled)

### Claim 27 (depends on 18)

The composition according to claim 18, wherein the targeting moiety binds to prostate-specific membrane antigen (PSMA).

### Claim at position 17

28-29. (canceled)

### Claim 30 (depends on 18)

The composition according to claim 18, wherein the targeting moiety binds to a somatostatin receptor (SSTR).

### Claim 31

(canceled)

### Claim 32 (depends on 18)

The composition according to claim 18, wherein the targeting moiety binds to a fibroblast activation protein (FAP).

### Claim at position 21

33-43. (canceled)

### Claim 44 (depends on 1)

A method of generating an image of a subject, comprising:
administering to the subject a composition according to claim 1, wherein *Cu is 61Cu; and
generating an image of at least a part of the subject's body.

### Claim at position 23

45-48. (canceled)

### Claim 49 (depends on 1)

A method of detecting a disease in a subject, comprising:
administering to the subject the composition according to claim 1, wherein *Cu is [61Cu]Cu; and
detecting the localization of the radiotracer; and
determining the presence or absence of the disease based on the presence or absence of localization of the radiotracer.

### Claim at position 25

50-57. (canceled)

### Claim 58 (depends on 1)

A method of monitoring or determining the effect of cancer treatment on a subject afflicted with cancer, comprising:
administering to the subject the composition according to claim 1, at an earlier time point, wherein *Cu is 61Cu; and at a later time point;
detecting the localization of the radiotracer at both the earlier time point and at the later time point; and
monitoring or determining the effect of the cancer treatment by comparing the amount of localization at the later time point to the amount of localization at the earlier time point.

### Claim at position 27

59-71. (canceled)

### Claim 72 (depends on 2)

A method of making a composition according to claim 2, the method comprising:
combining a copper radionuclide and a compound of Formula X:
or is a pharmaceutically acceptable salt thereof,
wherein:
is a chelating moiety:
L is a bond or a linker moiety;
V is the targeting moiety;
n is an integer selected from 1 to 10;
m is an integer selected from 1 to 10; and
p is an integer selected from 1 to 10.

### Claim at position 29

73-74. (canceled)

### Claim 75 (depends on 2)

The composition according to claim 2, wherein the radiotracer is of Formula A*:
or is a pharmaceutically acceptable salt thereof,
wherein
n is 1; and
the chelating moiety comprises NODAGA.

### Claim 76 (depends on 75)

The composition according to claim 75, wherein the targeting moiety binds to PSMA, SSTR, or FAP.

### Claim 77 (depends on 2)

The composition according to claim 2, wherein *Cu is 61Cu.

### Claim 78 (depends on 77)

The composition according to claim 77, wherein the composition has a molar activity ≥8 MBq/nmol.

### Claim 79 (depends on 78)

The composition according to claim 78, wherein the composition has a molar activity ≥20 MBq/nmol.

### Claim 80 (depends on 77)

The composition according to claim 77, wherein the composition has a radiochemical purity of ≥95%.

### Claim 81 (depends on 80)

The composition according to claim 80, wherein the composition has a radiochemical purity of ≥97%.

### Claim 82 (depends on 77)

The composition according to claim 77, wherein the composition has an activity concentration of ≥8 MBq/mL.

### Claim 83 (depends on 82)

The composition according to claim 82, wherein the composition has an activity concentration of ≥15 MBq/mL.

### Claim 84 (depends on 77)

The composition according to claim 77, wherein the radiotracer has a radionuclidic purity characterized by one or more of the following:
110mAg≤0.1 Bq/g;
108mAg≤0.1 Bq/g; and
109Cd≤0.1 Bq/g.

### Claim 85 (depends on 77)

The composition according to claim 77, wherein the radiotracer has a chemical purity characterized by one or more of the following:
Fe≤2 μg/L;
69Cu and 65Cu together are ≤1 μg/L;
Zn≤2 μg/L;
Sn≤0.01 μg/L;
Ti≤0.01 μg/L;
Al≤2 μg/L;
As≤1 μg/L;
Ni≤1 μg/L; and
wherein any one of Cr, Cd, Co, and Y is ≤0.1 μg/mL.