# US 10,500,293 B2 · Compositions, methods, and systems for the synthesis and use of imaging agents

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- Number: US 10,500,293 B2
- Document ID: US10500293B2
- Status: Granted
- Kind: B2
- Application number: 15/884,833
- Filed: 2018-01-31
- Published: 2018-11-08
- Granted: 2019-12-10
- Earliest claimed: 2012-08-10
- Assignees: Lantheus Medical Imaging, Inc.
- Applicants: Lantheus Medical Imaging, Inc.
- Inventors: Richard R. Cesati; Heike S. Radeke; Suresh K. Pandey; Ajay Purohit; Simon P. Robinson
- Web page: https://patentgrep.com/patent/US10500293B2

## CPC

- A61K 51/0459: {having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine}
- A61K 49/0004: {Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions}
- B01J 19/24: Stationary reactors without moving elements inside (B01J19/08, B01J19/26 take precedence; with stationary particles B01J8/02)
- C07B 59/002: {Heterocyclic compounds}
- C07D 237/04: having less than three double bonds between ring members or between ring members and non-ring members
- C07D 237/14: Oxygen atoms
- C07D 237/16: Two oxygen atoms
- C07D 311/56: without hydrogen atoms in position 3
- C07D 401/12: linked by a chain containing hetero atoms as chain links
- C07D 403/12: linked by a chain containing hetero atoms as chain links
- C07F 7/0812: {comprising a heterocyclic ring}
- C07F 7/12: Organo silicon halides
- B01J 2219/24: Stationary reactors without moving elements inside
- 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)
- B01J: CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22)

## Abstract

The present invention provides compounds with imaging moieties for imaging a subject. The present invention also relates to systems, compositions, and methods for the synthesis and use of imaging agents, or precursors thereof. An imaging agent precursor may be converted to an imaging agent using the methods described herein. In some cases, a composition or plurality of imaging agents is enriched in 18F. In some cases, an imaging agent may be used to image an area of interest in a subject, including, but not limited to, the heart, cardiovascular system, cardiac vessels, brain, and other organs.

## Claims

### Claim 1

A compound comprising the formula:
or a pharmaceutically acceptable salt thereof, wherein:
R20 is selected from the group consisting of hydrogen, heteroalkyl optionally substituted, alkoxy optionally substituted, alkoxyalkyl optionally substituted, aryl optionally substituted, heteroaryl optionally substituted, halo, haloalkyl, —CN, and —NO2;
each R21 and R23 is independently selected from the group consisting of hydrogen, alkyl optionally substituted, heteroalkyl optionally substituted, alkoxy optionally substituted, alkoxyalkyl optionally substituted, halo, haloalkyl, and an imaging moiety, or optionally any two R21 or any two R23 may be joined together to form a ring;
R22 is selected from the group consisting of hydrogen, alkyl optionally substituted, heteroalkyl optionally substituted, alkoxyalkyl optionally substituted, halo, haloalkyl, —OR28, —Si(R9)3, —B(R9′)3, and an imaging moiety;
R24, R25, R26, and R27 are each independently selected from the group consisting of hydrogen, alkyl optionally substituted, alkenyl optionally substituted, alkynyl optionally substituted, heteroalkyl optionally substituted, alkoxy optionally substituted, aryloxy optionally substituted, heteroaryloxy optionally substituted, alkoxyalkyl optionally substituted, aryl optionally substituted, heteroaryl optionally substituted, halo, haloalkyl, —NO2, —OH, —C(═O)R8, —C(═O)OR8, —OC(═O)R8, —C(═O)N(R7)2, —N(R7)C(═O)R8, —CN, and an imaging moiety;
each R7 is independently selected from the group consisting of hydrogen, alkyl optionally substituted, alkenyl optionally substituted, alkynyl optionally substituted, heteroalkyl optionally substituted, alkoxy optionally substituted, alkoxyalkyl optionally substituted, aryl optionally substituted, heteroaryl optionally substituted, halo, haloalkyl, and an imaging moiety, or optionally, any two R7 may be joined together to form a ring; and
each R8 is independently selected from the group consisting of hydrogen, alkyl optionally substituted, heteroalkyl optionally substituted, alkoxyalkyl optionally substituted, aryl optionally substituted, heteroaryl optionally substituted, haloalkyl, and an imaging moiety;
each R9 is independently selected from the group consisting of hydrogen, alkyl optionally substituted, aryl optionally substituted, haloalkyl, halogen, and an imaging moiety;
each R9′ is independently selected from the group consisting of halo, alkyl optionally substituted, aryl optionally substituted, and an imaging moiety;
R28 is selected from the group consisting of hydrogen, alkyl optionally substituted, and heteroalkyl optionally substituted;
G is O, S, or NR28;
a is 0, 1, 2, 3, or 4;
each K is independently arylene, heteroarylene, alkenylene, or alkynylene, each optionally substituted;
each b is independently 0, 1, 2, 3, or 4; and
c is 1 or 2,
provided at least one imaging moiety is present in the compound.

### Claim 2

A compound comprising the formula:
or a pharmaceutically acceptable salt thereof, wherein:
each R21 and R23 is independently selected from the group consisting of hydrogen, alkyl optionally substituted, heteroalkyl optionally substituted, alkoxy optionally substituted, alkoxyalkyl optionally substituted, halo, haloalkyl, and an imaging moiety, or optionally any two R21 or any two R23 may be joined together to form a ring;
R22 is selected from the group consisting of hydrogen, alkyl optionally substituted, heteroalkyl optionally substituted, alkoxyalkyl optionally substituted, halo, haloalkyl, —OR28, —Si(R9)3, —B(R9′)3, and an imaging moiety;
R24, R25, R26, and R27 are each independently selected from the group consisting of hydrogen, alkyl optionally substituted, alkenyl optionally substituted, alkynyl optionally substituted, heteroalkyl optionally substituted, alkoxy optionally substituted, aryloxy optionally substituted, heteroaryloxy optionally substituted, alkoxyalkyl optionally substituted, aryl optionally substituted, heteroaryl optionally substituted, halo, haloalkyl, —NO2, —OH, —C(═O)R8, —C(═O)OR8, —OC(═O)R8, —C(═O)N(R7)2, —N(R7)C(═O)R8, —CN, and an imaging moiety;
each R7 is independently selected from the group consisting of hydrogen, alkyl optionally substituted, alkenyl optionally substituted, alkynyl optionally substituted, heteroalkyl optionally substituted, alkoxy optionally substituted, alkoxyalkyl optionally substituted, aryl optionally substituted, heteroaryl optionally substituted, halo, haloalkyl, and an imaging moiety, or optionally, any two R7 may be joined together to form a ring; each R8 is independently selected from the group consisting of hydrogen, alkyl optionally substituted, heteroalkyl optionally substituted, alkoxyalkyl optionally substituted, aryl optionally substituted, heteroaryl optionally substituted, haloalkyl, and an imaging moiety;
each R9 is independently selected from the group consisting of hydrogen, alkyl optionally substituted, aryl optionally substituted, haloalkyl, halogen, and an imaging moiety;
each R9′ is independently selected from the group consisting of halo, alkyl optionally substituted, aryl optionally substituted, and an imaging moiety;
R28 is selected from the group consisting of hydrogen, alkyl optionally substituted, and heteroalkyl optionally substituted;
R29 is selected from the group consisting of hydrogen, alkyl optionally substituted, heteroalkyl optionally substituted, aryl optionally substituted, heteroaryl optionally substituted, optionally substituted alkoxy, optionally substituted alkoxyalkyl, halo, haloalkyl, —CN, —NO2, and an imaging moiety;
G is O, S, or NR28;
a is 0, 1, 2, 3, or 4;
each K is independently arylene, heteroarylene, alkenylene, or alkynylene, each optionally substituted, provided at least one K is alkenylene, or alkynylene;
each b is independently 0, 1, 2, 3, or 4; and
c is 1 or 2,
provided at least one imaging moiety is present in the compound.

### Claim 3 (depends on 1)

A pharmaceutical composition comprising a compound or a salt thereof of claim 1, and optionally a pharmaceutically acceptable excipient.

### Claim 4 (depends on 1)

A sterile aqueous solution comprising a compound or a salt thereof of claim 1.

### Claim 5 (depends on 1)

A method of imaging a portion of a subject, comprising:
administering to the subject a compound or a salt thereof of claim 1; and
acquiring at least one image of a portion of the subject.

### Claim 6 (depends on 1)

A method of imaging a portion of a subject, comprising:
administering to a subject a compound or a salt thereof of claim 1;
detecting radiation emitted by the compound; and
forming an image therefrom.

### Claim 7 (depends on 1)

A diagnostic kit comprising one or more vials containing a precursor to a compound or a salt thereof of claim 1; and optionally other components.

### Claim 8 (depends on 1)

A method of imaging myocardial perfusion, comprising:
administering to a patient a compound or a salt thereof of claim 1; and
scanning the patient using diagnostic imaging.

### Claim 9 (depends on 1)

A method of detecting myocardial perfusion, comprising:
administering to a patient a compound or a salt thereof of claim 1; and
scanning the patient using diagnostic imaging.

### Claim 10 (depends on 1)

A method of monitoring myocardial perfusion, comprising:
administering to a patient a compound or a salt thereof of claim 1; and
scanning the patient using diagnostic imaging.

### Claim 11 (depends on 1)

The compound of claim 1, wherein Formula (IX) is of the structure:

### Claim 12 (depends on 1)

The compound of claim 1, wherein the imaging moiety is selected from the group consisting of 11C, 13N, 18F, 76Br, 123I, 124I, 125I, 131I, 99mTc, 95Tc, 111In, 62Cu, 64Cu, 67Ga, and 68Ga.

### Claim 13 (depends on 1)

The compound of claim 1, wherein the imaging moiety is 18F.

### Claim 14 (depends on 1)

The compound of claim 1, selected from:
and pharmaceutically acceptable salts thereof.

### Claim 15 (depends on 12)

The compound or pharmaceutically acceptable salt of claim 12, wherein the imaging moiety is 18F.