Metabolic magnetic resonance imaging (MRI) using hyperpolarized (HP) pyruvate is becoming a non‐invasive technique for diagnosing, staging, and monitoring response to treatment in cancer and other diseases. The clinically established method for producing HP pyruvate, dissolution dynamic nuclear polarization, however, is rather complex and slow. Signal Amplification By Reversible Exchange (SABRE) is an ultra‐fast and low‐cost method based on fast chemical exchange. Here, for the first time, we demonstrate not only in vivo utility, but also metabolic MRI with SABRE. We present a novel routine to produce aqueous HP [1‐¹³C]pyruvate‐d₃ for injection in 6 minutes. The injected solution was sterile, non‐toxic, pH neutral and contained ≈30 mM [1‐¹³C]pyruvate‐d₃ polarized to ≈11 % (residual 250 mM methanol and 20 μM catalyst). It was obtained by rapid solvent evaporation and metal filtering, which we detail in this manuscript. This achievement makes HP pyruvate MRI available to a wide biomedical community for fast metabolic imaging of living organisms.

Hyperpolarized (HP) tracers dramatically increase the sensitivity of magnetic resonance imaging (MRI) to monitor metabolism non-invasively and in vivo. Their production, however, requires an extra polarizing device (polarizer) whose complexity, operation and cost can exceed that of an MRI system itself. Furthermore, the lifetime of HP tracers is short and some of the enhancement is lost during transfer to the application site. Here, we present the production of HP tracers in water without an external polarizer: by Synthesis Amid the Magnet Bore, A Dramatically Enhanced Nuclear Alignment (SAMBADENA) is achieved within seconds, corresponding to a hyperpolarization of ∼20%. As transfer of the tracer is no longer required, SAMBADENA may permit a higher polarization at the time of detection at a fraction of the cost and complexity of external polarizers. This development is particularly promising in light of the recently extended portfolio of biomedically relevant para-hydrogen-tracers and may lead to new diagnostic applications.

Magnetic Resonance Imaging (MRI) is a powerful imaging tool but suffers from a low sensitivity that severely limits its use for detecting metabolism in vivo. Hyperpolarization (HP) methods have demonstrated MRI signal enhancement by several orders of magnitude, enabling the detection of metabolism with a sensitivity that was hitherto inaccessible. While it holds great promise, HP is typically relatively slow (hours), expensive (million $, €) and requires a dedicated device (“polarizer”). Recently, we introduced a new method that creates HP tracers without an external polarizer but within the MR-system itself based on parahydrogen induced polarization (PHIP): Synthesis Amid the Magnet Bore Allows Dramatically Enhanced Nuclear Alignment (SAMBADENA). To date, this method is the simplest and least cost-intensive method for hyperpolarized ¹³C-MRI. HP of P_13C > 20% was demonstrated for 5mM tracer solutions previously. Here, we present a setup and procedure that enabled the first in vivo application of SAMBADENA: Within seconds, a hyperpolarized angiography tracer was produced and injected into an adult mouse. Subsequently, fast ¹³C-MRI was acquired which exhibited the vena cava, aorta and femoral arteries of the rodent. This first SAMBADENA in vivo ¹³C-angiography demonstrates the potential of the method as a fast, simple, low-cost alternative to produce HP-tracers to unlock the vast but hidden powers of MRI.