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Home Projects 2nd call (2009) 1. Development of efficient and biologically compatible paramagnetic centers for DNP methods

1. Development of efficient and biologically compatible paramagnetic centers for DNP methods

Dr. A. Comment (EPFL) and Dr. B. van den Brandt (PSI) - PhD student: Tian Cheng

Project finished in May 2013.

The Dynamic Nuclear Polarization (DNP) method was developed during the past decades to produce polarized targets for nuclear and particle physics research. In this field the Sample Environment and Polarized Targets (SEPT) group at the Paul Scherrer Institute is amongst the most experienced teams. Recently, a novel dissolution technique which allows to dissolve DNP-enhanced solid-state sample to obtain a so-called “hyperpolarized” liquid has been applied to Magnetic Resonance Spectroscopy (MRS) and Magnetic Resonance Imaging (MRI)[1]. The dissolution DNP technique seems very promising for many in vivo and in vitro MRS/MRI studies and several applications using hyperpolarized 13C-labeled molecules have been reviewed by Golman and Petersson [2]. The clinical potential of the technique in tumor treatment was recently discussed [3].

The samples start out as frozen glassy solutions of the (labeled) molecule of MRS/MRI interest at high concentration, and a few tens of mM of suitable paramagnetic centers as polarizing agents (so far only free radicals have been used). After being polarized via DNP at very low temperature, the solid-state samples containing the molecules of interest and the paramagnetic centers will be dissolved in water. The dissolution step typically dilutes this by an order of magnitude. A hardware characteristic is that the DNP and the MRS/MRI are done in separate magnets, at different fields. The dissolved sample is usually transported from one to the other by blowing it through a thin plastic tube. The intrinsic limitation of the technique is the finite life time of the hyperpolarized state of the molecule, which is determined by the longitudinal relaxation time of the nuclei of interest. The hyperpolarized state cannot be recovered once the magnetization is destroyed and therefore, although it is very intense, the signal is only available for a limited amount of time. In addition, the toxicity issue due the presence of a few mM of free radical in the hyperpolarized solution has to be addressed and so far this problem has been largely overlooked.

The aim of the present study is to investigate new types of paramagnetic centers and new methods to hyperpolarize the nuclear spins of biologically interesting molecules in order to meet as many as possible of the followings requirements: low toxicity, longer longitudinal relaxation time in the liquid state, and larger polarization.

[1] J.H. Ardenkjaer-Larsen, B. Fridlund, A. Gram, G. Hansson, L. Hansson, M.H. Lerche, R. Servin, M. Thaning, and K. Golman, Proc. Nat. Acad. Sci. USA 100 (2003) 10158-63.

[2] K. Golman, and J.S. Petersson, Academic Radiology 13 (2006) 932-942.

[3] S.E. Day, M.I. Kettunen, F.A. Gallagher, D.E. Hu, M. Lerche, J. Wolber, K. Golman, J.H. Ardenkjaer-Larsen, and K.M. Brindle, Nat. Med. 13 (2007) 1382-1387.

Contact: Tian Cheng