Low‐cost LED‐based Photo‐CIDNP Enables Biocompatible Hyperpolarization of ¹⁹F for NMR and MRI at 7 T and 4.7 T

Abstract

Substrates containing 19F can serve as background‐free reporter molecules for NMR and MRI. However, in vivo applications are still limited due to the lower signal‐to‐noise ratio (SNR) when compared with 1H NMR. Although hyperpolarization can increase the SNR, to date, only photo‐chemically induced dynamic nuclear polarization (photo‐CIDNP) allows for hyperpolarization without harmful metal catalysts. Photo‐CIDNP was shown to significantly enhance 19F NMR signals of 3‐fluoro‐DL‐tyrosine in aqueous solution using flavins as photosensitizers. However, lasers were used for photoexcitation, which is expensive and requires appropriate protection procedures in a medical or lab environment. Herein, we report 19F MR hyperpolarization at 4.7 T and 7 T with a biocompatible system using a low‐cost and easy‐to‐handle LED‐based set‐up. First hyperpolarized 19F MR images could be acquired, because photo‐CIDNP enabled repetitive hyperpolarization without adding new substrates.

Exploration of the close chemical space of tryptophan and tyrosine reveals importance of hydrophobicity in CW-photo-CIDNP performances

“…The first anomalous lines related to CIDNP were serendipitously observed in 1967 independently by Bargon et al (1967) and Ward and Lawler (1967). The radical pair mechanism was proposed by Kaptein and Oosterhoff (1969) and by Closs (1969) 2 years after and remains the cornerstone of the CIDNP theory ever since. Kaptein demonstrated that the polarization arises from the formation and the recombination of a radical pair in a magnetic field.…”

“…Initially, our recent efforts have been to push the dye absorption towards more biocompatible wavelengths such as the near-infrared region (650-900 nm). In parallel, the performance of photo-CIDNP with a readily handled light source is a contemporary goal (Bernarding et al, 2018). These efforts yielded the discovery of the Atto Thio 12 (AT12) dye which monitored CW-photo-CIDNP experiments with a promising signal-to-noise enhancement (SNE) after laser irradiation at 450 nm (Sobol et al, 2019).…”

Single Fluorinated Agent for Multiplexed 19F‐MRI with Micromolar Detectability Based on Dynamic Exchange

“…Several strategies were proposed to enhance 19 F-MRI sensitivity including the use of high-end cryogenic rf coils, [20] paramagnetic relaxation enhancement, [21] crystallographic defect induction, [22] compressed-sensing-based schemes [23] and even hyperpolarization techniques. [24] The 19 F-GEST approach shown here offers an alternative strategy to detect very low levels of thermally polarized pools of fluorine-19 spins with readily available hardware and can open new avenues for the development of advanced molecular architectures for the growing field of hotspot 19 F-MRI, which, so far, has not been used for mapping targets at very low concentrations. 19 F-MRI signal overlaid on the 1 H-MRI of alive mouse anesthetized with 4% G 4 .f,g) 19 F-ISIS-GEST data of two voxels acquired from the regions injected with f) H 2 :G 4 (magenta) and g) H 7 :G 4 (green).…”

Exploration of the close chemical space of tryptophan and tyrosine reveals importance of hydrophobicity in photo-CIDNP performances

“…Initially, our recent efforts have been to push the dye absorption towards more biocompatible wavelength such as near infrared (650-900 nm). In parallel, the performing of photo-CIDNP with readily handled light source is a contemporary goal (Bernarding et al, 2018). These efforts yielded to the discovery of the Atto Thio 12 (AT12) dye which monitored photo-CIDNP experiments with a promising signal-to-noise enhancement (SNE) after laser irradiation at 450 nm (Sobol et al, 2019).…”