Thermal annihilation of photo-induced radicals following dynamic nuclear polarization to produce transportable frozen hyperpolarized 13C-substrates

Abstract

Hyperpolarization via dynamic nuclear polarization (DNP) is pivotal for boosting magnetic resonance imaging (MRI) sensitivity and dissolution DNP can be used to perform in vivo real-time 13C MRI. The type of applications is however limited by the relatively fast decay time of the hyperpolarized spin state together with the constraint of having to polarize the 13C spins in a dedicated apparatus nearby but separated from the MRI magnet. We herein demonstrate that by polarizing 13C with photo-induced radicals, which can be subsequently annihilated using a thermalization process that maintains the sample temperature below its melting point, hyperpolarized 13C-substrates can be extracted from the DNP apparatus in the solid form, while maintaining the enhanced 13C polarization. The melting procedure necessary to transform the frozen solid into an injectable solution containing the hyperpolarized 13C-substrates can therefore be performed ex situ, up to several hours after extraction and storage of the polarized solid.

Efficient Hyperpolarization of U‐13C‐Glucose Using Narrow‐Line UV‐Generated Labile Free Radicals

“…Moreover,t heir labile nature has proven to pave aw ay to nuclear polarization storage and transport. [7] In the present work we tackled the issue of providing dDNP UV-radical precursors not involved in any metabolic pathway and producing labile radicals with improved 13 C dDNP performance compared to UV-PA. To this end, we investigated the photochemical properties of two a-keto acids,t rimethylpyruvic acid (TriPA) and its methyl-deuterated form d 9 -TriPA ( Figure 1). The 13 Cd DNP performance was evaluated for hyperpolarization of [U-13 C 6 ,1,2,3,4,5,6,6-d 7 ]-dglucose.The generated UV-radicals proved to be versatile and highly efficient polarizing agents,p roviding,a fter dissolution and transfer (10 s), a 13 Cl iquid-state polarization of up to 32 %.…”

“…[7] In Figure 6wereport how the UV-TriPA(panel A) and UV-d 9 -TriPA( panel B) respond to temperature.T o compensate for the Boltzmann factor and taking into account the number of paramagnetic centers only,t he ESR signal intensity multiplied by the temperature was plotted as af unction of the latter.T he characteristic "step function" profile clearly shows that all radicals are suddenly quenched above 190 K. Thus,t he samples became diamagnetic when still frozen. [7] In Figure 6wereport how the UV-TriPA(panel A) and UV-d 9 -TriPA( panel B) respond to temperature.T o compensate for the Boltzmann factor and taking into account the number of paramagnetic centers only,t he ESR signal intensity multiplied by the temperature was plotted as af unction of the latter.T he characteristic "step function" profile clearly shows that all radicals are suddenly quenched above 190 K. Thus,t he samples became diamagnetic when still frozen.…”

Preservation of Nuclear Spin Order by Precipitation

“…The UV-induced radicals are quenched when the sample is warmed. [5] It is also possible to immobilize the radicals by attachment to am atrix, so that they remain behind when the polarizedm ateriali sf lushedo ut. [9,10] In this paper we demonstrate the possibility of ad ifferent procedure, in which ap olarized solution is prepared and the sample precipitated to form as uspension of microcrystals.…”

“…[1][2][3][4][5][6][7][8][9][10] Clinical studies involving hyperpolarized [1-13 C]pyruvate have been used to monitor tumour metabolism. [2] In vivo imaging studies have also been performed using hyperpolarized [1-13 C]fumarate.…”

“…[1][2][3][4][5][6][7][8][9][10] Clinical studies involving hyperpolarized [1-13 C]pyruvate have been used to monitor tumour metabolism. [2] In vivo imaging studies have also been performed using hyperpolarized [1][2][3][4][5][6][7][8][9][10][11][12][13] C]fumarate. [3] Hyperpolarization methods are limited by an intrinsic longitudinalr elaxation time (T 1 )t hat governst he return of nonequilibriumm agnetization to thermal equilibrium.T he time for extractingt he sample from the hyperpolarizatione quipment, purification, transport, delivery,a nd signal acquisition is often similar to the nuclear T 1 ,m eaning that the polarizer needs to be located close to the point of use.…”