First in-human evaluation of [1-(13)C]pyruvate in D(2)O for hyperpolarized MRI of the brain: A safety and feasibility study Journal Article

   

Authors:	Deh, K.; Zhang, G.; Park, A. H.; Cunningham, C. H.; Bragagnolo, N. D.; Lyashchenko, S.; Ahmmed, S.; Leftin, A.; Coffee, E.; Hricak, H.; Miloushev, V.; Mayerhoefer, M.; Keshari, K. R.
Article Title:	First in-human evaluation of [1-(13)C]pyruvate in D(2)O for hyperpolarized MRI of the brain: A safety and feasibility study
Abstract:	Purpose: To investigate the safety and value of hyperpolarized (HP) MRI of [1-13C]pyruvate in healthy volunteers using deuterium oxide (D2O) as a solvent. Methods: Healthy 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. Results: All 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. Conclusions: HP [1-13C]pyruvate in D2O is safe for human imaging and provides an increase in T1 and SNR that may improve image quality. © 2024 International Society for Magnetic Resonance in Medicine.
Keywords:	controlled study; area under the curve; drug safety; nuclear magnetic resonance imaging; magnetic resonance imaging; quality control; analytic method; signal noise ratio; ph; cohort analysis; diagnostic imaging; simulation; oxides; feasibility study; image enhancement; brain; feasibility studies; image quality; in-vitro; normal human; human experiment; carbon; carbon isotopes; solvent; solvents; pyruvic acid; echo planar imaging; diagnostic test accuracy study; metabolites; carbon 13; procedures; deuterium oxide; deuterium; endotoxin; relaxation time; hyperpolarized; hyperpolarization; humans; human; male; female; article; pyruvates; healthy volunteers; hyperpolarized [1; safety studies; deuterium oxide (d<sub>2</sub>o); hyperpolarized <sup>13</sup>c-pyruvate; deuterium oxide (d2o); human evaluation; hyperpolarized 13c-pyruvate; filter integrity test; usp sterility test
Journal Title:	Magnetic Resonance in Medicine
Volume:	91
Issue:	6
ISSN:	0740-3194
Publisher:	John Wiley & Sons
Date Published:	2024-06-01
Start Page:	2559
End Page:	2567
Language:	English
DOI:	10.1002/mrm.30002
PUBMED:	38205934
PROVIDER:	scopus
PMCID:	PMC11009889
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85182158096&doi=10.1002%2fmrm.30002&partnerID=40&md5=30a0e9e0d1dc76c9a2a1cbd6746ebb14
Notes:	Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Kayvan Keshari -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/215828