First in‐human evaluation of [1‐13C]pyruvate in D2O for hyperpolarized MRI of the brain: A safety and feasibility study

Author:

Deh Kofi1ORCID,Zhang Guannan1,Park Angela Hijin2,Cunningham Charles H.34ORCID,Bragagnolo Nadia D.3ORCID,Lyashchenko Serge2,Ahmmed Shake2,Leftin Avigdor5,Coffee Elizabeth6,Hricak Hedvig17,Miloushev Vesselin1,Mayerhoefer Marius1,Keshari Kayvan R.17ORCID

Affiliation:

1. Department of Radiology, Memorial Sloan Kettering Cancer Center New York New York USA

2. Radiochemistry & Imaging Probes Core (RMIP), Memorial Sloan Kettering Cancer Center New York New York USA

3. Physical Sciences, Sunnybrook Research Institute Toronto Ontario Canada

4. Department of Medical Biophysics University of Toronto Toronto Ontario Canada

5. General Electric Healthcare New York New York USA

6. Department of Neurology Memorial Sloan Kettering Cancer Center New York New York USA

7. Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center New York New York USA

Abstract

AbstractPurposeTo investigate the safety and value of hyperpolarized (HP) MRI of [1‐13C]pyruvate in healthy volunteers using deuterium oxide (D2O) as a solvent.MethodsHealthy volunteers (n = 5), were injected with HP [1‐13C]pyruvate dissolved in D2O and imaged with a metabolite‐specific 3D dual‐echo dynamic EPI sequence at 3T at one site (Site 1). Volunteers were monitored following the procedure to assess safety. Image characteristics, including SNR, were compared to data acquired in a separate cohort using water as a solvent (n = 5) at another site (Site 2). The apparent spin–lattice relaxation time (T1) of [1‐13C]pyruvate was determined both in vitro and in vivo from a mono‐exponential fit to the image intensity at each time point of our dynamic data.ResultsAll volunteers completed the study safely and reported no adverse effects. The use of D2O increased the T1 of [1‐13C]pyruvate from 66.5 ± 1.6 s to 92.1 ± 5.1 s in vitro, which resulted in an increase in signal by a factor of 1.46 ± 0.03 at the time of injection (90 s after dissolution). The use of D2O also increased the apparent relaxation time of [1‐13C]pyruvate by a factor of 1.4 ± 0.2 in vivo. After adjusting for inter‐site SNR differences, the use of D2O was shown to increase image SNR by a factor of 2.6 ± 0.2 in humans.ConclusionsHP [1‐13C]pyruvate in D2O is safe for human imaging and provides an increase in T1 and SNR that may improve image quality.

Funder

National Institutes of Health

Publisher

Wiley

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