Temperature Cycling Enables Efficient 13C SABRE-SHEATH Hyperpolarization and Imaging of [1-13C]Pyruvate

Patrick TomHon; Mustapha Abdulmojeed; Isaiah Adelabu; Shiraz Nantogma; Mohammad Shah Hafez Kabir; Sören Lehmkuhl; Eduard Y. Chekmenev; Thomas Theis

doi:10.26434/chemrxiv-2021-cpz32

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Temperature Cycling Enables Efficient 13C SABRE-SHEATH Hyperpolarization and Imaging of [1-13C]Pyruvate

Shiraz Nantogma·Patrick TomHon·Mustapha Abdulmojeed·Isaiah Adelabu·Shiraz Nantogma·Mohammad Shah Hafez Kabir·Sören Lehmkuhl·Eduard Y. Chekmenev·Thomas Theis

August 2, 2021DOI: 10.26434/chemrxiv-2021-cpz32

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Abstract

Current metabolic imaging in humans is dominated by positron emission tomography (PET) methods. An emerging non-ionizing alternative for molecular imaging is hyperpolarized MRI. In particular, imaging of hyperpolarized 13C-pyruvate is a leading candidate because pyruvate is innocuous and has a central role in metabolism. However, simi-lar to PET, hyperpolarized MRI with dynamic nuclear polarization (DNP) is complex, costly and requires complex in-frastructure. In contrast, signal amplification by reversible exchange (SABRE) is a fast, cheap, and scalable hyperpo-larization technique. In particular, SABRE in SHield Enables Alignment Transfer to Heteronuclei (SABRE-SHEATH) transfers polarization from parahydrogen to 13C in pyruvate, however, to date, SABRE-SHEATH of 13C-pyruvate was limited in polarization levels relative to DNP (1.7% with SABRE-SHEATH vs. ~60% with DNP). Here we introduce a temperature cycling method for SABRE-SHEATH that enables >10% polarization on [1-13C]pyruvate, sufficient for successful in vivo experiments. First, at lower temperatures, ~20% polarization is accumulated on SABRE-catalyst bound pyruvate, which is subsequently released into free pyruvate in solution at elevated temperatures. We take ad-vantage of the achieved polarization to demonstrate first 13C pyruvate images with a cryogen-free MRI system operat-ed at 1 T. This illustrates that inexpensive hyperpolarization methods can be combined with low-cost MRI systems to obtain a broadly available, yet highly sensitive metabolic imaging platform.

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TomHon, P., Abdulmojeed, M., Adelabu, I., Nantogma, S., Kabir, M., Lehmkuhl, S., Chekmenev, E., & Theis, T. (2021). Temperature Cycling Enables Efficient 13C SABRE-SHEATH Hyperpolarization and Imaging of [1-13C]Pyruvate. Unpublished manuscript. https://doi.org/10.26434/chemrxiv-2021-cpz32

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Temperature Cycling Enables Efficient 13C SABRE-SHEATH Hyperpolarization and Imaging of [1-13C]Pyruvate

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