Broadband method for signal amplification of magnetic resonance contrast agents within seconds and their purification

The method according to one of the preceding claims, wherein said sequence of radio frequency pulses further comprises a first 90° radio frequency pulse (RF1) having a phase φ11 and acting on the protons, wherein the first group (NA) of 180° radio frequency pulses is consecutively applied nA times during said first time interval (τA) after said first 90° radio frequency pulse (RF1), and wherein said sequence of radio frequency pulses further comprises a second 90° radio frequency pulse (RF2) having a phase φ12 and acting on the protons, which second 90° radio frequency pulse (RF2) succeeds the first 90° radio frequency pulse (RF1) and is applied to the protons at an end of the first time interval (τA), wherein the second group (NB) of 180° radio frequency pulses is consecutively applied ng times during said second time interval (τB) after said second 90° radio frequency pulse (RF2), and wherein said sequence of radio frequency pulses further comprises a third 90° radio frequency pulse (RF3) having a phase φ13 and acting on the protons, which third 90° radio frequency pulse (RF3) succeeds the second 90° radio frequency pulse (RF2) and is applied to the protons at an end of the second time interval (τB), wherein the third group (NC) of 180° radio frequency pulses is consecutively applied nC times during said third time interval (τC) after said third 90° radio frequency pulse (RF3).

The method according to one of the preceding claims, wherein for obtaining a hyperpolarized contrast agent comprising the at least one heteronucleus (S3), prior to said step of applying a sequence of radio frequency pulses to the protons and the at least one heteronucleus in order to transfer said two-spin order into the hyperpolarization of the at least one heteronucleus (S3), said molecule is added to one of:

• a mediator, the mediator not being part of the hyperpolarized contrast agent in the end,
• a precursor of the hyperpolarized contrast agent, which precursor is finally part of the hyperpolarized contrast agent, wherein the at least one heteronucleus (S3) is comprised by the precursor,
• a precursor of the hyperpolarized contrast agent, which precursor is then split to obtain the contrast agent that comprises the at least one heteronucleus (S3).
• a contrast agent, wherein the at least one heteronucleus is comprised by the contrast agent.

The method according to one of the preceding claims, wherein

• said hyperpolarization of the at least one heteronucleus is conducted with help of a catalyst in an organic solvent, wherein after hyperpolarization of the at least one heteronucleus, an aqueous solution is added to the organic solvent, and wherein the aqueous solution may comprise a cleaving agent that is configured to cleave a precursor comprising the at least one hyperpolarized heteronucleus to obtain a hyperpolarized contrast agent, and wherein for capturing the catalyst a complexing agent can be added to the organic solvent before or after adding the aqueous solution to the organic solvent, and wherein the organic solvent is evaporated or removed by using a stripping gas, and wherein for obtaining an injectable solution comprising the contrast agent, the aqueous solution is filtered to remove by-products and/or impurities that precipitated upon evaporation;
• or wherein
• said hyperpolarization of the at least one heteronucleus forming part of a contrast agent is conducted in a solvent, the solvent being one of:
• an aqueous solution, an organic solution, a mixture of an aqueous and an organic solution, wherein the solvent is evaporated or removed by using a stripping gas, leaving the hyperpolarized contrast agent behind, particularly in a solid form, and wherein the contrast agent is washed with a solvent in which the contrast agent does not dissolve, and wherein for obtaining an injectable solution comprising the contrast agent, the contrast agent is added to a solution.

A method for obtaining an injectable solution comprising a contrast agent, wherein

• a hyperpolarization of at least one heteronucleus is conducted with help of a catalyst in an organic solvent, wherein after hyperpolarization of the at least one heteronucleus, an aqueous solution is added to the organic solvent, and wherein the aqueous solution may comprise a cleaving agent that is configured to cleave a precursor comprising the at least one hyperpolarized heteronucleus to obtain a hyperpolarized contrast agent, and wherein for capturing the catalyst a complexing agent can be added to the organic solvent before or after adding the aqueous solution to the organic solvent, and wherein the organic solvent is evaporated or removed by using a stripping gas, and wherein for obtaining an injectable solution comprising the contrast agent, the aqueous solution is filtered to remove by-products and/or impurities that precipitated upon evaporation;
• or wherein
• a hyperpolarization of at least one heteronucleus forming part of a contrast agent is conducted in a solvent, the solvent being one of:
• an aqueous solution, an organic solution, a mixture of an aqueous and an organic solution, wherein the solvent is evaporated or removed by using a stripping gas, leaving the hyperpolarized contrast agent behind, particularly in a solid form, and wherein the contrast agent is washed with a solvent in which the contrast agent does not dissolve, and wherein for obtaining an injectable solution comprising the contrast agent, the contrast agent is added to a solution.