NMR Hyperpolarization of Established PET Tracers

Abstract

The development of sensitive probes for directly measuring in vivo processes is at the forefront of medical imaging. In the case of magnetic resonance imaging (MRI) the detection of a small number of molecules is a major challenge due to its limited sensitivity. This problem can be tackled by hyperpolarization, which increases the NMR signals up to several orders of magnitude. In this contribution NMR hyperpolarization of non-radioactive counterparts of two well-established positron emission tomography (PET) tracers, namely O-(2-[ 18 F] fluoroethyl)-l-tyrosine ([ 18 F]FET) and [ 18 F]fallypride ([ 18 F]FP), via para-hydrogen induced polarization (PHIP), to investigate oncological and neurological questions is demonstrated. Significant 1 H/ 13 C NMR signal enhancements of several thousand were achieved for both tracers. Partial deuteration of the 13 Clabeled [ 18 F]FET analog resulted in T 1 times up to~36 s. Hence, this molecule is a candidate for an MRI contrast agent, allowing follow-up MRI examinations with close succession in time.Magnetic resonance imaging (MRI) has revolutionized medical diagnostics due to its rich content of anatomical information, high resolution and non-invasiveness. However, its relatively low sensitivity caused by the minute nuclear spin polarization even at high magnetic fields, remains a significant drawback. In particular the detection of a very small number of molecules, as it is feasible by e. g. positron emission tomography (PET), is a huge issue for MRI applications. A strategy to overcome the hurdle of NMR sensitivity is presented by nuclear spin hyperpolarization (HP). Different HP techniques have been developed that create non-equilibrium nuclear spin populations compared to the thermal distribution, e. g. dynamic nuclear polarization (DNP) [1] and para-hydrogen induced polarization (PHIP) [2] which allow for NMR signal enhancements (SE) of several orders of magnitude. These techniques enable in vivo molecular imaging by MRI with high temporal and spatial resolution. [3] But still, medical applications are often limited by the finite lifetime of the HP state which is subject to nuclear spin lattice relaxation (T 1 ). Therefore, HP MRI was mostly realized by hyperpolarizing heteronuclei, such as 13 C. [3] This approach combines three advantages: (i) long T 1 relaxation times resulting in a longer lifetime of the HP state, (ii) the negligible natural background signal of 13 C in vivo and (iii) the large isotropic chemical shift range of 13 C, which allows an improved distinction of different molecular species. However, so far only very few molecules have been successfully hyperpolarized to a level which allows to apply them for in vivo MRI, most of them being part of the citric acid cycle, e. g. pyruvate, [4] acetate, [5] and succinate. [6] Yet, HP of tracers that are able to target specific diseases is still sparse. Here, MRI scientists can be inspired by PET, for which a large number of sophisticated tracers addressing various diseases have been developed. [7] However, due to...

Discrimination of PHIP Signals Through their Evolution in Multipulse Sequences

“…One alternative is the use of hollow membranes or tubes for delivering the parahydrogen into the sample. [49] In a previous publication, [48] we presented a reaction chamber constructed with hollow Teflon tubes (more details can be found in the ESI of Ref. [48]) which gives full control of the hydrogenation reaction.…”