Compositions, methods, and systems for the synthesis and use of imaging agents

Patent metadata

Field	Value
Publication number	US-10500293-B2
Application number	US-201815884833-A
Country	US
Kind code	B2
Filing date	Jan 31, 2018
Priority date	Aug 10, 2012
Publication date	Dec 10, 2019
Grant date	Dec 10, 2019

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.

First claim

What is claimed:

1. A compound comprising the formula:

or a pharmaceutically acceptable salt thereof, wherein:
R 20 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 —NO 2 ;
each R 21 and R 23 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 R 21 or any two R 23 may be joined together to form a ring;
R 22 is selected from the group consisting of hydrogen, alkyl optionally substituted, heteroalkyl optionally substituted, alkoxyalkyl optionally substituted, halo, haloalkyl, —OR 28 , —Si(R 9 ) 3 , —B(R 9′ ) 3 , and an imaging moiety;
R 24 , R 25 , R 26 , and R 27 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, —NO 2 , —OH, —C(═O)R 8 , —C(═O)OR 8 , —OC(═O)R 8 , —C(═O)N(R 7 ) 2 , —N(R 7 )C(═O)R 8 , —CN, and an imaging moiety;
each R 7 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 R 7 may be joined together to form a ring; and
each R 8 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 R 9 is independently selected from the group consisting of hydrogen, alkyl optionally substituted, aryl optionally substituted, haloalkyl, halogen, and an imaging moiety;
each R 9′ is independently selected from the group consisting of halo, alkyl optionally substituted, aryl optionally substituted, and an imaging moiety;
R 28 is selected from the group consisting of hydrogen, alkyl optionally substituted, and heteroalkyl optionally substituted;
G is O, S, or NR 28 ;
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.

2. A compound comprising the formula:

or a pharmaceutically acceptable salt thereof, wherein:
each R 21 and R 23 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 R 21 or any two R 23 may be joined together to form a ring;
R 22 is selected from the group consisting of hydrogen, alkyl optionally substituted, heteroalkyl optionally substituted, alkoxyalkyl optionally substituted, halo, haloalkyl, —OR 28 , —Si(R 9 ) 3 , —B(R 9′ ) 3 , and an imaging moiety;
R 24 , R 25 , R 26 , and R 27 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, —NO 2 , —OH, —C(═O)R 8 , —C(═O)OR 8 , —OC(═O)R 8 , —C(═O)N(R 7 ) 2 , —N(R 7 )C(═O)R 8 , —CN, and an imaging moiety;
each R 7 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 R 7 may be joined together to form a ring; each R 8 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 R 9 is independently selected from the group consisting of hydrogen, alkyl optionally substituted, aryl optionally substituted, haloalkyl, halogen, and an imaging moiety;
each R 9′ is independently selected from the group consisting of halo, alkyl optionally substituted, aryl optionally substituted, and an imaging moiety;
R 28 is selected from the group consisting of hydrogen, alkyl optionally substituted, and heteroalkyl optionally substituted;
R 29 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, —NO 2 , and an imaging moiety;
G is O, S, or NR 28 ;
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.

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

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

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. A method of monitoring myocardial perfusion, comprising:
administering to a patient a compound or a salt thereo

Assignees

• Lantheus Medical Imaging Inc

Inventors

• Cesati Richard R
• Radeke Heike S
• Pandey Suresh K
• Purohit Ajay
• Robinson Simon P

Classifications

• C07F7/0812

  comprising a heterocyclic ring · CPC title

• A61K51/0459 Primary

  having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine · CPC title

• B01J19/24

  Stationary reactors without moving elements inside (B01J19/08, B01J19/26 take precedence; with stationary particles B01J8/02) · CPC title

• C07D237/14

  Oxygen atoms · CPC title

• C07F7/12

  Organo silicon halides · CPC title