State-of-the-art accounts of hyperpolarized <sup>15</sup>N-labeled molecular imaging probes for magnetic resonance spectroscopy and imaging

Park, Hyejin; Wang, Qiu

doi:10.1039/d2sc01264b

Cited by 23 publications

(30 citation statements)

References 79 publications

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“…15 N generally offers longer T 1 relaxation times than 13 C due to its lower gyromagnetic ratio. 15 N labeled heteroaromatic molecules such as nicotinamide and metronidazole can be efficiently hyperpolarized using parahydrogen based methods (SABRE). − These compounds are also known to bind to albumin with a K a of around 10 5 M –1 and consequently, albumin binding is expected to shorten the 15 N T 1 values. , …”

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confidence: 99%

Competitive Displacement Restores the Hyperpolarized ¹⁵N NMR Signal in Blood Plasma

Suh

2022

ACS Phys. Chem Au

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Hyperpolarized (HP) NMR can improve the sensitivity of conventional NMR experiments by several orders of magnitude, thereby making it feasible to detect the signal of low sensitivity nuclei such as 13 C and 15 N nuclei in vivo. Hyperpolarized substrates are usually administered by direct injection into the bloodstream, and interaction with serum albumin can cause rapid decay of the hyperpolarized signal due to the shortening of the spin−lattice (T 1 ) relaxation time. Here we report that the 15 N T 1 of 15 N labeled, partially deuterated tris(2pyridylmethyl)amine decreases dramatically upon binding to albumin to such an extent that no HP-15 signal could be detected. We also demonstrate that the signal could be restored using a competitive displacer, iophenoxic acid, which binds stronger to albumin than tris(2-pyridylmethyl)amine. The methodology presented here eliminates the undesirable effect of albumin binding and should widen the range of hyperpolarized probes for in vivo studies.

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confidence: 99%

Competitive Displacement Restores the Hyperpolarized ¹⁵N NMR Signal in Blood Plasma

Suh

2022

ACS Phys. Chem Au

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“…The facile synthesis of 15 N-labeled anilines further demonstrates the utility of this method. 15 N-labeled compounds are of significance in studying the pharmacokinetics and metabolism of bioactive compounds are usually prepared by a nitration–reduction process with 15 N-labeled nitric acid as the nitrogen source. , As summarized in Table , using this light-driven Ni(II)-catalyzed C–N coupling reaction, 15 N-labeled anilines could be readily accessed with commercially available 15 NH 4 Cl, a cheaper and more conveniently handled nitrogen-15 source.…”

Section: Resultsmentioning

confidence: 99%

Photochemical Synthesis of Anilines via Ni-Catalyzed Coupling of Aryl Halides with Ammonium Salts

Song

Nong

et al. 2022

ACS Catal.

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Easy, efficient, and economic synthesis of anilines remains an important challenge in synthetic chemistry. In this study, a Ni(OAc) 2 -bipyridine complex is shown to readily catalyze the amination of aryl halides with ammonium salts under direct excitation of light, allowing a broad array of aryl chlorides and bromides to be converted into the corresponding primary (hetero)arylamines in the absence of an external photosensitizer. Late-stage modification of drug molecules and 15 N-labeling of primary aryl amines are also demonstrated with a number of examples. Photoinduced generation of Ni(I)-bipyridine species is believed to be the key step in the reaction, enabling a Ni(I)/Ni(III) cycle for catalytic turnover.

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“…With currently limited reports on in vivo studies of 15 N-probes, 15 N-BBCP presents exciting progress as an exogenous reaction-based 15 N-probe extended to in vivo imaging. While 15 N-BBCP was rationally designed to achieve the desired molecular reactivity, several factors need to be considered and improved for future studies.…”

Section: Resultsmentioning

confidence: 99%

“…Compared to carbon-13-labeled probes, nitrogen-15-labeled agents are relatively underexplored as hyperpolarization probes. Among the hyperpolarization studies reported, the 15 N-labeled hyperpolarized probes have shown great potentials to deliver a long T 1 and a wide range of 15 N chemical shift (900 ppm) for an extended scope of chemical complexity. − Notably, the T 1 of 15 N-trimethylphenylammonium was reportedly over 400 s although the oxidative reaction afforded a small chemical shift (∼1.5 ppm).…”

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Design and Characterization of Hyperpolarized ¹⁵N-BBCP as a H₂O₂-Sensing Probe

et al. 2022

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Hydrogen peroxide (H2O2) is a type of reactive oxygen species that regulates essential biological processes. Despite the central role of H2O2 in pathophysiological states, available molecular probes for assessing H2O2 in vivo are still limited. This work develops hyperpolarized 15N-boronobenzyl-4-cyanopyridinium (15N-BBCP) as a rationally designed molecular probe for detecting H2O2. The 15N-BBCP demonstrated favorable physicochemical and biochemical properties for H2O2 detection and dynamic nuclear polarization, allowing noninvasive detection of H2O2. In particular, 15N-BBCP and the products possessed long spin–lattice relaxation times and spectrally resolvable 15N chemical shift differences. The performance of hyperpolarized 15N-BBCP was demonstrated both in vitro and in vivo with time-resolved 15N-MRS. This study highlights a promising approach to designing a reaction-based 15N-labeled molecular imaging agent for detecting oxidative stress in vivo.

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State-of-the-art accounts of hyperpolarized ¹⁵N-labeled molecular imaging probes for magnetic resonance spectroscopy and imaging

Abstract: Hyperpolarized isotope-labeled agents have significantly advanced nuclear magnetic resonance spectroscopy and imaging (MRS/MRI) of physiochemical activities at molecular levels. An emerging advance in this area is exciting developments of 15N-labeled...

Cited by 23 publications

References 79 publications

Competitive Displacement Restores the Hyperpolarized ¹⁵N NMR Signal in Blood Plasma

Competitive Displacement Restores the Hyperpolarized ¹⁵N NMR Signal in Blood Plasma

Photochemical Synthesis of Anilines via Ni-Catalyzed Coupling of Aryl Halides with Ammonium Salts

Design and Characterization of Hyperpolarized ¹⁵N-BBCP as a H₂O₂-Sensing Probe

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State-of-the-art accounts of hyperpolarized 15N-labeled molecular imaging probes for magnetic resonance spectroscopy and imaging

Abstract: Hyperpolarized isotope-labeled agents have significantly advanced nuclear magnetic resonance spectroscopy and imaging (MRS/MRI) of physiochemical activities at molecular levels. An emerging advance in this area is exciting developments of 15N-labeled...

Cited by 23 publications

References 79 publications

Competitive Displacement Restores the Hyperpolarized 15N NMR Signal in Blood Plasma

Competitive Displacement Restores the Hyperpolarized 15N NMR Signal in Blood Plasma

Photochemical Synthesis of Anilines via Ni-Catalyzed Coupling of Aryl Halides with Ammonium Salts

Design and Characterization of Hyperpolarized 15N-BBCP as a H2O2-Sensing Probe

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State-of-the-art accounts of hyperpolarized ¹⁵N-labeled molecular imaging probes for magnetic resonance spectroscopy and imaging

Competitive Displacement Restores the Hyperpolarized ¹⁵N NMR Signal in Blood Plasma

Competitive Displacement Restores the Hyperpolarized ¹⁵N NMR Signal in Blood Plasma

Design and Characterization of Hyperpolarized ¹⁵N-BBCP as a H₂O₂-Sensing Probe