Monitoring brain dopamine synthesis by MRS (Bio-X)
- Reference number
- A3 05:171
- Start and end dates
- 050101-080630
- Amount granted
- 5 065 250 SEK
- Administrative organization
- Lund University
- Research area
- Life Science Technology
Summary
BX-063 Kirik - Golman Monitoring brain dopamine synthesis by MRS Project Summary: Objectives, expected results, summary of the Project plan The goal of the project is to develop and validate a novel approach for non-invasive imaging of neurotransmitter function in the brain based on Magnetic Resonance Spectroscopy (MRS). The Bio-Partner has a longstanding expertise and an international position in disease modeling and in studies of the dopamine system in the brain, with special emphasis on animal models of Parkinson´s disease. The X-Partner has pioneered the development of an exciting new technique for ultra-sensitive detection and quantification of tracer compounds using MRS. This technique is based on hyperpolarization of 13C-labelled compounds, which increases the MR signal emitted by 13Clabeledcompounds dramatically, by up to 4-5 orders of magnitude. In this program, the two partners will join forces to apply the hyperpolarization technique for real-time in vivo measurement of dopamine synthesis and turnover in the brain. Hyperpolarized 13C-labelled DOPA and 13C-labelled tyrosine will be used as tracers for imaging of the conversion of DOPA to dopamine (by the enzyme aromatic acid decarboxylase), and the conversion of tyrosine to DOPA (by the enzyme tyrosine hydroxylase). After optimization in an in vitro test system the technique will be tested and validated in vivo in experiments in rats and pigs. If successful, this approach will allow, for the first time, non-invasive measurement and possibly also regional imaging of DA synthesis and turnover in the brain, a technique that could have important use for studies of dopamine neuron function, and as a diagnostic tool, in a wide variety of neurological and psychiatric disorders. Keywords for the project (to be found in international databases) Dopamine, L-DOPA, tyrosine, Parkinson’s disease, magnetic resonance spectroscopy, in vivo imaging, 13Clabelling, hyperpolarization, molecular imaging.