# US 12,214,058 B2 · Imaging methods using deuterated compounds

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- Number: US 12,214,058 B2
- Document ID: US12214058B2
- Status: Granted
- Kind: B2
- Application number: 18/056,856
- Filed: 2022-11-18
- Published: 2023-07-13
- Granted: 2025-02-04
- Earliest claimed: 2014-05-13
- Assignees: Genentech, Inc.
- Applicants: Genentech, Inc.
- Inventors: Jan Marik; Joseph P. Lyssikatos; Simon Peter Williams
- Web page: https://patentgrep.com/patent/US12214058B2

## CPC

- A61K 51/0459: {having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine}
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07B 59/002: {Heterocyclic compounds}
- C07D 487/04: Ortho-condensed systems
- 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)
- 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)
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

The present invention relates to deuterated and optionally detectably labeled compounds of formula (I) and formula (V): and salts thereof, wherein R1, R2, A, and X10-X19 have any of the values defined in the specification. Also included are pharmaceutical compositions comprising such compounds and salts, and methods of using such compounds and salts as imaging agents.

## Claims

### Claim 1

A method for detecting one or more of neurofibrillary tangles, senile plaques, or tau protein aggregation in a human subject, the method comprising:
obtaining a three-dimensional image of the subject's brain;
administering to the human subject an effective amount of a radiolabeled tracer selected from:
or a pharmaceutically acceptable salt thereof, wherein the effective amount is sufficient to provide an initial radiation level not greater than 370 MBq;
acquiring three-dimensional images of the subject's brain with a PET camera at one or more time intervals, thereby providing a 3D PET image of the radioactive signal of the tracer at each of the one or more time intervals;
aligning the PET images with one another and, using the MR volumetric image for anatomical delineation, identifying irregular regions of interest in the subject's brain;
measuring the standardized uptake value ratio for each region of interest relative to cerebellum gray at each of the one or more time intervals; and
identifying regions having enhanced standardized uptake value ratios as containing one or more of: neurofibrillary tangles, senile plaques, or tau protein aggregation.

### Claim 2 (depends on 1)

The method of claim 1 wherein the image is a MR volumetric image.

### Claim 3 (depends on 1)

The method of claim 1, wherein the irregular regions are in one or more of the frontal, parietal, occipital, temporal lobes, cerebellum gray, and white matter.

### Claim 4 (depends on 1)

The method of claim 1, wherein the deuterated carbon of any of the tracers has a deuterium isotopic enrichment factor of at least 3500.

### Claim 5 (depends on 1)

The method of claim 1, wherein the tracer is:

### Claim 6

A method of detecting a neurological disorder, Alzheimer's disease, or progressive supranuclear palsy in a human subject, the method comprising:
obtaining a three-dimensional image of the subject's brain;
administering to the human subject an effective amount of a radiolabeled tracer selected from:
or a pharmaceutically acceptable salt thereof, wherein the effective amount is sufficient to provide an initial radiation level not greater than 370 MBq;
acquiring three-dimensional images of the subject's brain with a PET camera at one or more time intervals, thereby providing a 3D PET image of the radioactive signal of the tracer at each of the one or more time intervals;
aligning the PET images with one another and, using the MR volumetric image for anatomical delineation, identifying irregular regions of interest in the subject's brain;
measuring the standardized uptake value ratio for each region of interest relative to cerebellum gray at each of the one or more time intervals;
identifying one or more regions having enhanced standardized uptake value ratios as containing one or more of: neurofibrillary tangles, senile plaques, or tau protein aggregation; and
correlating the one or more regions having enhanced standardized uptake value ratios with onset of neurological disorder, Alzheimer's disease, or progressive supranuclear palsy in the subject.