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

Molecular metabolic imaging in humans is dominated by positron emission tomography (PET). An emerging nonionizing alternative is hyperpolarized MRI of C-13-pyruvate, which is innocuous and has a central role in metabolism. However, similar to PET, hyperpolarized MRI with dissolution dynamic nuclear polarization (d-DNP) is complex costly, and requires significant infrastructure. In contrast, Signal Amplification By Reversible Exchange (SABRE) is a fast, cheap, and scalable hyperpolarization technique. SABRE in SHield Enables Alignment Transfer to Heteronuclei (SABRE-SHEATH) can transfer polarization from parahydrogen to C-13 in pyruvate; however, polarization levels remained low relative to d-DNP (1.7% with SABRE-SHEATH versus approximate to 60% with DNP). Here we introduce a temperature cycling method for SABRE-SHEATH that enables >10% polarization on [1-C-13]-pyruvate, sufficient for successful in vivo experiments. First, at lower temperatures, approximate to 20% polarization is accumulated on SABRE catalyst-bound pyruvate, which is released into free pyruvate at elevated temperatures. A kinetic model of differential equations is developed that explains this effect and characterizes critical relaxation and buildup parameters. With the large polarization, we demonstrate the first(13)C pyruvate images with a cryogen-free MRI system operated at 1.5 T, illustrating that inexpensive hyperpolarization methods can be combined with low-cost MRI systems to obtain a broadly available, yet highly sensitive metabolic imaging platform.