Hyperpolarized 1-13C-1,1-bis(acetoxy(methyl))-2,2′-cyclopropane as metabolic marker for MR

Patent metadata

Field	Value
Publication number	US-10583209-B2
Application number	US-201916363193-A
Country	US
Kind code	B2
Filing date	Mar 25, 2019
Priority date	Jul 1, 2013
Publication date	Mar 10, 2020
Grant date	Mar 10, 2020

Abstract

1- 13 C-1,1-Bis(acetoxy(methyl))-2,2′-cyclopropane of formula (I):

The compound can be hyperpolarized and used as a contrast agent in 13 C Magnetic Resonance diagnostic technique ( 13 C-MR) for the diagnosis of tumor.

First claim

The invention claimed is:

1. A method for operating an MRI system comprising the steps of:
a. administering a solution of hyperpolarized compound 1- 13 C-1,1-Bis(acetoxy(methyl))-2,2′-cyclopropane to a subject who is affected or suspected to be affected by a tumor, submitting the subject to a radiation having a frequency selected to excite nuclear spin transitions in 13 C nuclei;
b. detecting an MR signal from said excited nuclei of at least one hyperpolarized metabolic product selected from the group consisting of 1- 13 C-1-(acetoxy(methyl))-1-(hydroxy(methyl))-2,2′-cyclopropane and 1- 13 C-1, 1-(dihydroxy(methyl))-2,2′-cyclopropane; and
c. comparing a first MR signal deriving from a region of interest comprising said tumor or said suspected tumor with a second MR signal deriving from said subject or from a sample taken from said subject.

2. The method according to claim 1 further comprising the steps of:
d. determining a difference between said first signal and second signal;
e. comparing said difference of step d) with a reference value, to produce a deviation value; and
f. determining if the deviation value is, in absolute value, higher than a predetermined value.

3. The method according to claim 2 , wherein said second signal is determined on a non-tumor tissue, further comprising the step of:
g. providing an indication of possible tumor affection in case the deviation value is in absolute value higher than said predetermined value.

4. The method according to claim 2 , wherein said second signal is determined in the region of interest, at an earlier moment in time with respect to the first signal, and optionally stored in the system, said method further comprising the step of:
g′ providing an indication of tumor variation in case the deviation is in absolute value higher than said predetermined value.

5. The method according to claim 2 , wherein said subject has undergone an anti-tumor treatment and wherein said second signal is determined in the region of interest, at an earlier moment in time with respect to said first signal, and optionally stored in the system, said method further comprising the step of:
g″ providing an indication of efficacy of said treatment if this deviation is in absolute value higher than a predetermined value.

6. The method according to claim 5 wherein said second signal is determined before, after or at the beginning of the treatment.

7. A method for operating an MRI system comprising the steps of:
a. administering a solution of hyperpolarized deuterated compound 1- 13 C-1,1-Bis(acetoxy(methyl))-2,2′-cyclopropane of formula (II):

 to a subject who is affected or suspected to be affected by a tumor, submitting the subject to a radiation having a frequency selected to excite nuclear spin transitions in 13 C nuclei;
b. detecting an MR signal from said excited nuclei of at least one hyperpolarized metabolic product selected from the group consisting of 1- 13 C-1-(acetoxy(methyl-d 2 ))-1-(hydroxy(methyl-d 2 ))-2,2′-d 4 -cyclopropane and 1- 13 C-1, 1-(dihydroxy(methyl-d 2 ))-2,2′-d 4 -cyclopropane; and
c. comparing a first MR signal deriving from a region of interest comprising said tumor or said suspected tumor with a second MR signal deriving from said subject or from a sample taken from said subject.

8. The method according to claim 7 further comprising the steps of:
d. determining a difference between said first signal and second signal;
e. comparing said difference of step d) with a reference value, to produce a deviation value; and
f. determining if the deviation value is, in absolute value, higher than a predetermined value.

9. The method according to claim 8 , wherein said second signal is determined on a non-tumor tissue, further comprising the step of:
g. providing an indication of possible tumor affection in case the deviation value is in absolute value higher than said predetermined value.

10. The method according to claim 8 , wherein said second signal is determined in the region of interest, at an earlier moment in time with respect to the first signal, and optionally stored in the system, said method further comprising the step of:
g′ providing an indication of tumor variation in case the deviation is in absolute value higher than said predetermined value.

11. The method according to claim 8 , wherein said subject has undergone an anti-tumor treatment and wherein said second signal is determined in the region of interest, at an earlier moment in time with respect to said first signal, and optionally stored in the system, said method further comprising the step of:
g″ providing an indication of efficacy of said treatment if this deviation is in absolute value higher than a predetermined value.

12. The method according to claim 11 wherein said second signal is determined before, after or at the beginning of the treatment.

Assignees

• Bracco Imaging Spa

Inventors

• Lerche Mathilde H
• Jensen Pernille Rose
• Karlsson Magnus
• Napolitano Roberta
• Cabella Claudia
• Miragoli Luigi
• Colombo Serra Sonia
• Tedoldi Fabio

Classifications

• C07B59/001

  Acyclic or carbocyclic compounds · CPC title

• C07B2200/05

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

• A61K51/0402 Primary

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

• C07C2601/02

  with a three-membered ring · CPC title

• A61B5/4848

  Monitoring or testing the effects of treatment, e.g. of medication · CPC title