SABRE-SHEATH Hyperpolarization of [1,5- 13 C 2 ]Z-OMPD for Noninvasive pH Sensing.

Autor: Abdulmojeed MB; Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695, United States., Grashei M; Technical University of Munich, School of Medicine and Health, Department of Nuclear Medicine, TUM University Hospital, D-81675 Munich, Germany., Dilday S; Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695, United States., Wodtke P; Technical University of Munich, School of Medicine and Health, Department of Nuclear Medicine, TUM University Hospital, D-81675 Munich, Germany., McBride S; Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695, United States., Davidsson A; Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695, United States., Curran E; Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695, United States., MacCulloch K; Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695, United States., Browning A; Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695, United States., TomHon P; Vizma Life Sciences, Chapel Hill, North Carolina 27514, United States., Schmidt AB; Division of Medical Physics, Department of Radiology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Killianstr. 5a, Freiburg 79106, Germany.; German Cancer Consortium (DKTK), Partner Site Freiburg, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany.; Department of Chemistry, Integrated Biosciences (Ibio), Wayne State University, Karmanos Center Institute (KCI), Detroit, Michigan 48202, United States., Chekmenev EY; Department of Chemistry, Integrated Biosciences (Ibio), Wayne State University, Karmanos Center Institute (KCI), Detroit, Michigan 48202, United States., Schilling F; Technical University of Munich, School of Medicine and Health, Department of Nuclear Medicine, TUM University Hospital, D-81675 Munich, Germany.; German Cancer Consortium (DKTK), Partner Site Munich, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany., Theis T; Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695, United States.; Department of Physics, North Carolina State University, Raleigh, North Carolina 27695, United States.
Jazyk: angličtina
Zdroj: ACS sensors [ACS Sens] 2024 Dec 27; Vol. 9 (12), pp. 6372-6381. Date of Electronic Publication: 2024 Nov 18.
DOI: 10.1021/acssensors.4c01102
Abstrakt: Hyperpolarized (HP) 13 C-labeled probes are emerging as promising agents to noninvasively image pH in vivo. HP [1,5- 13 C 2 ]Z-OMPD (Z-4-methyl-2-oxopent-3-enedioic acid) in particular has recently been used to simultaneously report on kidney perfusion, filtration, and pH homeostasis, in addition to the ability to detect local tumor acidification. In previous studies, dissolution dynamic nuclear polarization was used to hyperpolarize Z-OMPD. Here, we pioneered the hyperpolarization of [1,5- 13 C 2 ]Z-OMPD via SABRE-SHEATH (signal amplification by reversible exchange in shield enabling alignment transfer to heteronuclei), which is relatively simple and fast and promises to be highly scalable. With SABRE-SHEATH, we achieve enhancement values of ∼3950 and ∼2400 at 1.1 T ( P 13C = 0.4 and 0.25%) on the labeled C-1 and C-5 positions of Z-OMPD. Density functional theory calculations at the B3LYP level of theory were used to investigate possible binding modes of Z-OMPD on the iridium-based polarization transfer catalyst. The experimental and theoretical results suggest that the equatorial binding mode to the catalyst, where Z-OMPD binds to the catalyst at both C-1 and C-5 carboxylate positions, is the most stable complex. The HP signals were used to measure the Z-OMPD chemical shift as a function of pH showing an ∼3 ppm shift across pH 4-11. This work lays a foundation for the development of a simple, low-cost hyperpolarization technique to image pH.
Databáze: MEDLINE
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