Method for investigating the fate of a test compound or the stateof a biological system by means of NMR of hyperpolarised NMR active nuclei
View Patent ↗The invention is concerned with Nuclear Magnetic Resonance (NMR) spectroscopy and Magnetic Resonance Imaging (MRI), particularly NMR spectroscopy. It provides hyperpolarization methods offering enhanced sensitivity of detection over conventional NMR for studying the fate of a test compound in a biological system. The methods are particularly suitable for studying metabolism and toxicity of drugs. The resulting NMR sensitivity increase is advantageous in two key aspects of NMR detection: test compounds can be detected at lower concentrations and substantial time saving can be achieved in cases where extensive averaging is conventionally employed to increase the signal to noise ratio of the corresponding NMR spectra. The methods can be used for studios that were not practical or not possible using conventional NMR.
1. A method for investigating the fate of a test compound, said method comprising the steps of:
administering the test compound to a biological system in which the fate of the test compound is to be studied, wherein the test compound is enriched with 13 C;
extracting samples from the system over time;
hyperpolarising the NMR active nuclei in the samples extracted from the system over time, wherein said hyperpolarising is carried out by polarization transfer using solid state dynamic nuclear polarization (DNP) effected by a DNP agent;
subjecting the samples to a treatment resulting in solid to liquid phase transition; and
analysing each of said samples by NMR spectroscopy in the liquid state.
2. A method according to claim 1 , wherein the hyperpolarised sample is retained in a holding field in the period from hyperpolarisation to analysis.
3. A method according to claim 1 , wherein the metabolism of a test compound is studied.
4. A method according to claim 1 , wherein the system is one of a whole animal and a human body.
5. A method according to claim 1 for studying absorption of a test compound wherein the system is one of a whole animal and a human body.