Fluorinated beta-hydroxybutyric acids for PET imaging

Patent metadata

Field	Value
Publication number	US-11833228-B2
Application number	US-202016992940-A
Country	US
Kind code	B2
Filing date	Aug 13, 2020
Priority date	Aug 14, 2019
Publication date	Dec 5, 2023
Grant date	Dec 5, 2023

Abstract

Beta-hydroxybutyric acid-based radiopharmaceuticals, pharmaceutical compositions comprising same, methods for preparing same, and methods of using same for diagnostic imaging and non-imaging tracer studies are provided.

First claim

What is claimed is:

1. A compound of:
(a) (S)-[ 18 F]γ-fluoro-β-hydroxybutyric acid having the absolute stereochemistry of formula (I):

wherein the hydroxylated carbon at position 3 has (S) stereochemistry;
or a pharmaceutically acceptable salt, solvate, or hydrate thereof; or
(b) (R)-[ 18 F]γ-fluoro-β-hydroxybutyric acid having the absolute stereochemistry of formula (II):

wherein the hydroxylated carbon at position 3 has (R) stereochemistry;
or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

2. A composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier.

3. A method for diagnosing, staging, or treating a disorder in a subject comprising:
administering a radiopharmaceutical to the subject; and
imaging an organ or tissue of interest using positron emission tomography;
wherein the radiopharmaceutical comprises the compound of (S)-[ 18 F]γ-fluoro-β-hydroxybutyric acid having the absolute stereochemistry of formula (I)

wherein the hydroxylated carbon at position 3 has (S) stereochemistry, (R)-[ 18 F]γ-fluoro-β-hydroxybutyric acid having the absolute stereochemistry of formula (II)

wherein the hydroxylated carbon at position 3 has (R) stereochemistry, or a pharmaceutically acceptable salt, solvate, hydrate, or composition thereof, and is capable of being retained within the organ or tissue sufficient to emit positrons for detection by positron emission tomography.

4. The method of claim 3 wherein the disorder is selected from Alzheimer's disease, epilepsy, cancer, cardiovascular disease, or diabetes.

5. The method of claim 4 , wherein the cardiovascular disease is heart failure.

6. The method of claim 4 , wherein the cancer is breast cancer.

7. The method of claim 3 , wherein the organ or tissue is selected from the brain, breast, heart, eye, or a tumor.

8. A method for monitoring a disorder in a subject comprising:
administering a radiopharmaceutical to a subject undergoing medical treatment for the disorder;
imaging an organ or tissue of interest using positron emission tomography; and
comparing the quantity or distribution of the radiopharmaceutical present in the subject with a control quantity or distribution indicative of the effectiveness of the medical treatment;
wherein the radiopharmaceutical comprises the compound of (S)-[ 18 F]γ-fluoro-β-hydroxybutyric acid having the absolute stereochemistry of formula (I) wherein the hydroxylated carbon at position 3 has (S) stereochemistry, (R)-[ 18 F]γ-fluoro-β-hydroxybutyric acid having the absolute stereochemistry of formula (II) wherein the hydroxylated carbon at position 3 has (R) stereochemistry, or a pharmaceutically acceptable salt, solvate, hydrate, or composition thereof, and is capable of being retained within the organ or tissue sufficient to emit positrons for detection by positron emission tomography.

9. The method of claim 8 , wherein the disorder is selected from Alzheimer's disease, epilepsy, cancer, cardiovascular disease, or diabetes.

10. The method of claim 9 , wherein the cardiovascular disease is heart failure.

11. The method of claim 9 , wherein the cancer is breast cancer.

12. The method of claim 8 , wherein the organ or tissue is selected from the brain, breast, heart, eye, or a tumor.

13. The method of claim 8 , wherein the medical treatment is ketogenic diet therapy.

Assignees

• Univ Alberta

Inventors

• Mattingly Stephanie
• Wuest Frank
• Schirrmacher Ralf
• Wuest Melinda
• Fine Eugene

Classifications

• A61K51/0402 Primary

  carboxylic acid carriers, fatty acids (amino acids A61K51/0406) · CPC title

• A61P5/00

  Drugs for disorders of the endocrine system · CPC title

• C07B59/001

  Acyclic or carbocyclic compounds · CPC title

• C07C53/21

  containing fluorine · CPC title

• C07B2200/05

  Isotopically modified compounds, e.g. labelled · CPC title