Imaging histone deacetylases with a radiotracer using positron emission tomography

Patent metadata

Field	Value
Publication number	US-10188756-B2
Application number	US-201415030214-A
Country	US
Kind code	B2
Filing date	Oct 17, 2014
Priority date	Oct 18, 2013
Publication date	Jan 29, 2019
Grant date	Jan 29, 2019

Abstract

Disclosed herein are histone deacetylase imaging agents for positron emission tomography and related imaging methods using the histone deacetylase imaging agents. The histone deacetylase imaging agents may be a compound of formula (I): wherein R 1 is a moiety including a positron emitter; R 2 represents hydrogen, or substituted or unsubstituted alkyl, or substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and n is an integer selected from 0 or 1. In one version of the compound of formula (I), R 1 is a moiety including an adamantyl group.

First claim

What is claimed is:

1. A compound of formula (I):

wherein R 1 is a moiety including a substituted or unsubstituted adamantyl group and a contrast agent,
wherein R 2 represents hydrogen, or substituted or unsubstituted alkyl, or substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or substituted or unsubstituted heterocyclic, and
wherein n is an integer selected from 0 or 1, and
wherein the compound has a brain to plasma ratio greater than 1, and wherein at least one atom in R 1 is replaced with a positron emitter selected from the group consisting of 11 C, 13 N, 15 O, 18 F, 34m Cl, 38 K, 45 Ti, 51 Mn, 52m Mn, 52 Fe, 55 Co, 60 Cu, 61 Cu, 62 Cu, 64 Cu, 66 Ga, 68 Ga, 71 As, 72 As, 74 As, 75 Br, 76 Br, 82 Rb, 86 Y, 89 Zr, 90 Nb, 94m Tc, 110m In, 118 Sb, 120 I, 121 I, 122 I, and 124 I.

2. The compound of claim 1 wherein:
the positron emitter is 11 C or 18 F.

3. The compound of claim 1 wherein:
the contrast agent is a photon emitter.

4. The compound of claim 3 wherein:
the photon emitter is selected from the group consisting of 67 Ga, 99m Tc, 111 In, 123 I, 125 I, 131 I, and 201 TI.

5. The compound of claim 1 wherein:
the contrast agent is a contrast agent for magnetic resonance imaging.

6. The compound of claim 5 wherein:
the magnetic resonance imaging contrast agent is selected from the group consisting of ions of gadolinium, manganese, and iron.

7. The compound of claim 1 wherein:
the compound has an octanol-water partition coefficient (log D) in the range of 1 to 3.

8. The compound of claim 1 wherein:
n is 1.

9. A method for in vivo imaging of a subject, the method comprising:
(a) administering to the subject the compound of claim 1 ;
(b) waiting a time sufficient to allow the compound to accumulate at a tissue or cell site to be imaged; and
(c) imaging the cells or tissues with a non-invasive imaging technique.

10. The method of claim 9 wherein:
the non-invasive imaging technique is selected from positron emission tomography imaging, positron emission tomography with computed tomography imaging, or positron emission tomography with magnetic resonance imaging.

11. A method for detecting histone deacetylase in a subject, the method comprising:
(a) administering to the subject the compound of claim 1 ;
(b) waiting a time sufficient to allow the compound to accumulate at a tissue or cell site in a brain of the subject to be imaged; and
(c) imaging the cells or tissues with a non-invasive imaging technique.

Assignees

• Massachusetts Gen Hospital

Inventors

• Hooker Jacob M
• Wang Changning
• Schroeder Frederick Albert

Classifications

• C07D209/08

  with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring · CPC title

• C07D235/08

  Radicals containing only hydrogen and carbon atoms · CPC title

• C07C2602/10

  the other ring being six-membered, e.g. tetraline · CPC title

• C07B2200/05

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

• C07D281/12

  condensed with two six-membered rings · CPC title