Host and intestinal microbiota derived metabolomic blood plasma signature for prior radiation injury

Patent metadata

Field	Value
Publication number	US-11092591-B2
Application number	US-201515518284-A
Country	US
Kind code	B2
Filing date	Nov 13, 2015
Priority date	Nov 21, 2014
Publication date	Aug 17, 2021
Grant date	Aug 17, 2021

Abstract

Provided are methods of determining prior radiation dose exposure levels for subjects, and kits therefor. Also provided are methods of treatment.

First claim

What is claimed is:

1. A kit for determining a dose of radiation that a subject has been exposed to, the kit comprising:
a mass spectrometer for quantifying a concentration of each metabolite in a plurality of metabolites;
a receptacle into which a body fluid sample from the subject is placed, and which is connectable to the mass spectrometer so that the mass spectrometer can measure the concentration of each metabolite of the plurality of metabolites in the sample;
a non-transitory computer-readable medium coupled to one or more data processing apparatus having instructions stored thereon which, when executed by the one or more data processing apparatus, cause the one or more data processing apparatus to perform a method for determining the dose of radiation that the subject has been exposed to by implementing an algorithm on a data set comprising the concentration of each metabolite of the plurality of metabolites in the sample so as to determine the dose of radiation that the subject has been exposed to by correlating the concentration of each metabolite of the plurality of metabolites with the received dose of radiation;
a visual display and/or audible signal that indicates the dose of radiation that the subject has been exposed to, wherein the dose of radiation that the subject has been exposed to is determined to be only one of:
1 to 2 Gy;
2 to 4 Gy;
4 to 6 Gy;
6 to 8 Gy;
or greater than 8 Gy, and
wherein the plurality of metabolites consists of:
Thymidine
2′-Deoxyuridine
2-Aminobutyrate
2-Hydroxyisobutyrate
1-Eicosadienoylglycerophosphocholine
2-Palmitoylglycerophosphocholine
Ectoine
Homocitrulline
3-Hydroxypropanoate
Citrulline
1-Arachidonoylglycerophosphoethanolamine
Equol glucuronide
3-Phenyl propionate (hydrocinnamate)
Stachydrine
1-Palm itoleoylglycerophosphocholine
chiro -Inositol
Docosahexaenoate (DHA22:6n3)
gamma-Glutamylisoleucine
1-Arachidonoylglycerophosphoinositol
Eicosapentaenoate (EPA20:5n3)
Pipecolate
Dihomo-linolenate (20:3n3 or n6)
1-Myristoylglycerophosphocholine
2-Linoleoylglycerophosphoethanolamine
Salicylate
Phenol sulfate
N-acetylhistidine
4-Vinylphenol sulfate
1-Linoleoylglycerophosphoethanolamine
3-Indoxyl sulfate
p-Cresol sulfate
Indolelactate
1-Linoleoylglycerophosphoinositol
Homostachydrine
1-Palm itoylglycerophosphoinositol
Equol sulfate; and
Indolepropionate.

2. The kit of claim 1 , wherein the plurality of metabolites includes metabolites arising from at least one intestinal microbiota within the subject.

3. The kit of claim 1 , wherein the body fluid sample is selected from the group consisting of blood, plasma, or another a blood derivative.

4. The kit of claim 1 , wherein the subject is a human subject.

5. A method of determining a dose of radiation that a subject has been exposed to, comprising:
a) quantifying a concentration of each metabolite of a plurality of metabolites in a sample, wherein the sample is selected from the group consisting of blood, plasma, or another a blood derivative;
b) implementing an algorithm on a data set comprising the quantified concentrations of each metabolite of the plurality of metabolites so as to obtain an algorithm output;
c) correlating the algorithm output with the dose of radiation that the subject has been exposed to so as to determine the dose of radiation that the subject has been exposed to, wherein the dose of radiation that the subject has been exposed to is only one of
1 to 2 Gy;
2 to 4 Gy;
4 to 6 Gy;
6 to 8 Gy;
or greater than 8 Gy, and
wherein the plurality of metabolites consists of the following metabolites:
Thymidine
2′-Deoxyuridine
2-Aminobutyrate
2-Hydroxyisobutyrate
1-Eicosadienoylglycerophosphocholine
2-Palm itoylglycerophosphocholine
Ectoine
Homocitrulline
3-Hydroxypropanoate
Citrulline
1-Arachidonoylglycerophosphoethanolamine
Equol glucuronide
3-Phenyl propionate (hydrocinnamate)
Stachydrine
1-Palm itoleoylglycerophosphocholine
chiro -Inositol
Docosahexaenoate (DHA22:6n3)
gamma-Glutamylisoleucine
1-Arachidonoylglycerophosphoinositol
Eicosapentaenoate (EPA20:5n3)
Pipecolate
Dihomo-linolenate (20:3n3 or n6)
1-Myristoylglycerophosphocholine
2-Linoleoylglycerophosphoethanolamine
Salicylate
Phenol sulfate
N-acetylhistidine
4-Vinylphenol sulfate
1-Linoleoylglycerophosphoethanolamine
3-Indoxyl sulfate
p-Cresol sulfate
Indolelactate
1-Linoleoylglycerophosphoinositol
Homostachydrine
1-Palm itoylglycerophosphoinositol
Equol sulfate; and
Indolepropionate.

6. The method of claim 5 , wherein the plurality of metabolites arises from the subject and from at least one intestinal microbiota of the subject.

7. The method of claim 5 , wherein the body fluid sample is blood plasma.

8. The method of claim 5 , wherein the method is performed within 24 hours after the subject is exposed to the dose of radiation.

9. The method of claim 5 , wherein the method is performed within 48 hours after the subject is exposed to the dose of radiation.

10. The method of claim 5 , wherein the concentrations of each metabolite of the plurality of metabolites are quantified using a mass spectrometer.

11. A system comprising:
one or more data processing apparatus; and
a non-transitory computer-readable medium coupled to the one or more data processing apparatus having instructions stored thereon which, when executed by the one or more data processing apparatus, cause the one or more data processing apparatus to perform a method for determining a dose of radiation that a subject has been exposed to, comprising:
a) quantifying a concentration of each metabolite in a plurality of metabolites in a sample obtained from the subject, wherein the plurality of metabolites consists of:
Thymidine
2′-Deoxyuridine
2-Aminobutyrate
2-Hydroxyisobutyrate
1-Eicosadienoylglycerophosphocholine
2-Palmitoylglycerophosphocholine
Ectoine
Homocitrulline
3-Hydroxypropanoate
Citrulline
1-Arachidonoylglycerophosphoethanolamine
Equol glucuronide
3-Phenyl propionate (hydrocinnamate)
Stachydrine
1-Palmitoleoylglycerophosphocholine
chiro -Inositol
Docosahexaenoate (DHA22:6n3)
gamma-Glutamylisoleucine
1-Arachidonoylglycerophosphoinositol
Eicosapentaenoate (EP A20: 5n3)
Pipecolate
Dihomo-linolenate (20:3n3 or n6)
1-Myristoylglycerophosphocholine
2-Linoleoylglycerophosphoethanolamine
Salicylate
Phenol sulfate
N-acetylhistidine
4-Vinylphenol sulfate
1-Linoleoylglycerophosphoethanolamine
3-Indoxyl sulfate
p-Cresol sulfate
Indolelactate
1-Linoleoylglycerophosphoinositol
Homostachydrine
1-Palmitoylglycerophosphoinositol
Equol sulfate
Indolepropionate;
b) implementing an algorithm on a data set that comprises the concentrations of each metabolite in the plurality of metabolites so as to obtain an algorithm output;
c) determining the dose of radiation that the subject has been exposed to after implementing the algorithm output, wherein the dose of radiation that the subject has been exposed to is only one of:
1 to 2 Gy;
2 to 4 Gy;
4 to 6 Gy;
6 to 8 Gy;
or greater than 8 Gy.

Assignees

• Albert Einstein College Medicine

Inventors

• Golden Aaron Alain-Jon
• Broin Pilib Ó
• Guha Chandan
• Kurland Irwin

Classifications

• G01N30/72

  Mass spectrometers {(mass spectrometers per se H01J49/00)} · CPC title

• G01T1/04

  Chemical dosimeters (G01T1/06, G01T1/08 take precedence) · CPC title

• G01N33/6848 Primary

  Methods of protein analysis involving mass spectrometry · CPC title

• G01N30/88

  Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 · CPC title

• G01N2570/00

  Omics, e.g. proteomics, glycomics or lipidomics; Methods of analysis focusing on the entire complement of classes of biological molecules or subsets thereof, i.e. focusing on proteomes, glycomes or lipidomes · CPC title