TY - JOUR

T1 - A versatile synthetic route to the preparation of 15N heterocycles

AU - Chukanov, Nikita V.

AU - Kidd, Bryce E.

AU - Kovtunova, Larisa M.

AU - Bukhtiyarov, Valerii I.

AU - Shchepin, Roman V.

AU - Chekmenev, Eduard Y.

AU - Goodson, Boyd M.

AU - Kovtunov, Kirill V.

AU - Koptyug, Igor V.

N1 - © 2018 John Wiley & Sons, Ltd.

PY - 2019/11/1

Y1 - 2019/11/1

N2 - A robust medium-scale (approximately 3 g) synthetic method for 15N labeling of pyridine (15N-Py) is reported based on the Zincke reaction. 15N enrichment in excess of 81% was achieved with approximately 33% yield. 15N-Py serves as a standard substrate in a wide range of studies employing a hyperpolarization technique for efficient polarization transfer from parahydrogen to heteronuclei; this technique, called SABRE (signal amplification by reversible exchange), employs a simultaneous chemical exchange of parahydrogen and a to-be-hyperpolarized substrate (e.g., pyridine) on metal centers. In studies aimed at the development of hyperpolarized contrast agents for in vivo molecular imaging, pyridine is often employed either as a model substrate (for hyperpolarization technique development, quality assurance, and phantom imaging studies) or as a co-substrate to facilitate more efficient hyperpolarization of a wide range of emerging contrast agents (e.g., nicotinamide). Here, the produced 15N-Py was used for the feasibility study of spontaneous 15N hyperpolarization at high magnetic (HF) fields (7 T and 9.4 T) of an NMR spectrometer and an MRI scanner. SABRE hyperpolarization enabled acquisition of 2D MRI imaging of catalyst-bound 15N-pyridine with 75 × 75 mm2 field of view (FOV), 32 × 32 matrix size, demonstrating the feasibility of 15N HF-SABRE molecular imaging with 2.4 × 2.4 mm2 spatial resolution.

AB - A robust medium-scale (approximately 3 g) synthetic method for 15N labeling of pyridine (15N-Py) is reported based on the Zincke reaction. 15N enrichment in excess of 81% was achieved with approximately 33% yield. 15N-Py serves as a standard substrate in a wide range of studies employing a hyperpolarization technique for efficient polarization transfer from parahydrogen to heteronuclei; this technique, called SABRE (signal amplification by reversible exchange), employs a simultaneous chemical exchange of parahydrogen and a to-be-hyperpolarized substrate (e.g., pyridine) on metal centers. In studies aimed at the development of hyperpolarized contrast agents for in vivo molecular imaging, pyridine is often employed either as a model substrate (for hyperpolarization technique development, quality assurance, and phantom imaging studies) or as a co-substrate to facilitate more efficient hyperpolarization of a wide range of emerging contrast agents (e.g., nicotinamide). Here, the produced 15N-Py was used for the feasibility study of spontaneous 15N hyperpolarization at high magnetic (HF) fields (7 T and 9.4 T) of an NMR spectrometer and an MRI scanner. SABRE hyperpolarization enabled acquisition of 2D MRI imaging of catalyst-bound 15N-pyridine with 75 × 75 mm2 field of view (FOV), 32 × 32 matrix size, demonstrating the feasibility of 15N HF-SABRE molecular imaging with 2.4 × 2.4 mm2 spatial resolution.

KW - N

KW - contrast agent

KW - hyperpolarization

KW - MRI

KW - parahydrogen

KW - PHIP

KW - pyridine

UR - http://www.scopus.com/inward/record.url?scp=85059604774&partnerID=8YFLogxK

U2 - 10.1002/jlcr.3699

DO - 10.1002/jlcr.3699

M3 - Article

C2 - 30537260

AN - SCOPUS:85059604774

VL - 62

SP - 892

EP - 902

JO - Journal of Labelled Compounds and Radiopharmaceuticals

JF - Journal of Labelled Compounds and Radiopharmaceuticals

SN - 0362-4803

IS - 13

ER -