Hyperpolarized product selective saturating‐excitations for determination of changes in metabolic reaction rates in real‐time. (2nd December 2019)

• Record Type: Journal Article
• Authors: Harris, Talia; Uppala, Sivaranjan; Lev‐Cohain, Naama; Adler‐Levy, Yael; Shaul, David; Nardi‐Schreiber, Atara; Sapir, Gal; Azar, Assad; Gamliel, Ayelet; Sosna, Jacob; Gomori, J. Moshe; Katz‐Brull, Rachel
• Is Part Of: NMR in biomedicine. Volume 33:Number 2(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-12-02
• Subjects: [1‐13C]pyruvate -- alanine -- bicarbonate -- brain slices -- hyperpolarized 13C‐NMR -- lactate -- liver slices -- MCF7 tumors; Nuclear magnetic resonance -- Periodicals; Magnetic Resonance Spectroscopy -- Periodicals; 574
• DOI: 10.1002/nbm.4189
• Languages: English
• ISSNs: 0952-3480

Abstract

Abstract : Investigation of hyperpolarized substrate metabolism has been showing utility in real‐time determination of in‐cell and in vivo enzymatic activities. Intracellular reaction rates may vary during the course of a measurement, even on the very short time scales of visibility on hyperpolarized MR, due to many factors such as the availability of the substrate and co‐factors in the intracellular space. Despite this potential variation, the kinetic analysis of hyperpolarized signals typically assumes that the same rate constant (and in many cases, the same rate) applies throughout the course of the reaction as observed via the build‐up and decay of the hyperpolarized signals. We demonstrate here an acquisition approach that can null the need for such an assumption and enable the detection of instantaneous changes in the rate of the reaction during an ex vivo hyperpolarized investigation, ( i.e . in the course of the decay of one hyperpolarized substrate dose administered to a viable tissue sample ex vivo ). This approach utilizes hyperpolarized product selective saturating‐excitation pulses. Similar pulses have been previously utilized in vivo for spectroscopic imaging. However, we show here favorable consequences to kinetic rate determinations in the preparations used. We implement this acquisition strategy for studies on perfused tissue slices and develop a theory that explains why this particular approach enables the determination of changes in enzymatic rates that are monitored via the chemical conversions of hyperpolarized substrates. Real‐time changes in intracellular reaction rates are demonstrated in perfused brain, liver, and xenograft breast cancer tissue slices and provide another potential differentiation parameter for tissue characterization. Abstract : Determination of enzymatic rates using hyperpolarized substrates and sampling by product selective saturating‐excitations is demonstrated. A theory is proposed to explain how instantaneous changes in reaction rate constants can be determined uniquely with this approach and biological proof that such changes actually exist and vary across tissues is provided.