Metabolic Tumor Imaging with Rapidly Signal‐Enhanced 1‐¹³C‐Pyruvate‐d₃

Abstract

The metabolism of malignant cells differs significantly from that of healthy cells and thus, it is possible to perform metabolic imaging to reveal not only the exact location of a tumor, but also intratumoral areas of high metabolic activity. Herein, we demonstrate the feasibility of metabolic tumor imaging using signal-enhanced 1-13 C-pyruvate-d 3 , which is rapidly enhanced via para-hydrogen, and thus, the signal is amplified by several orders of magnitudes in less than a minute. Using as a model, human melanoma xenografts injected with signal-enhanced 1-13 C-pyruvate-d3, we show that the conversion of pyruvate into lactate can be monitored along with its kinetics, which could pave the way for rapidly detecting and monitoring changes in tumor metabolism.

In Vivo Metabolic Imaging of [1-13C]Pyruvate-d3 Hyperpolarized By Reversible Exchange With Parahydrogen

“…A commercially available agent is a significant advantage compared to "hydrogenative" pH2-based hyperpolarization techniques that necessitate suitable unsaturated precursors for the permanent addition of pH2. [13,[17][18][19][20] Furthermore, SABRE offers some notable advantages over current dDNP methods, such as faster production and lower costs. Currently, the methods allow us to polarize a dose in less than 10 min, or several doses during one imaging session (i.e.…”

“…Parahydrogen-induced polarization (PHIP) techniques have emerged as promising candidates to address this need for efficient polarization methods. [12][13][14][15][16][17][18][19][20][21][22][23][24][25] PHIP utilizes the nuclear spin singlet isomer of molecular hydrogen, parahydrogen (pH2), which acts as a cost-efficient source of hyperpolarization.…”

“…[2] The current advances in molecular tumor biology, genetics, and imaging technology have led to a major paradigm shift in oncology to utilize molecular imaging as a superior diagnostic and prognostic marker of cancer staging, response to treatment and survival. [ 18…”

Real-Time Pyruvate Chemical Conversion Monitoring Enabled by PHIP

“…The metabolic conversion of [1- 13 C]pyruvate-to-[1- 13 C]lactate (P−L) has shown potential in clinical trials of prostate cancer patients, 43−45 and we have recently used it to produce the first mouse tumor imaging by PHIP-SAH. 46 However, by approaching TCA, [1-13 C]pyruvate is converted via PDH into 13 CO 2 , thereby preventing the direct detection of downstream TCA metabolites. Instead, [2-13 C]pyruvate enters TCA and can potentially be used to access, for example, [5-13 C]glutamate, thus broadening the range of accessible metabolic information.…”

“…Among the various molecular systems, pyruvate plays a crucial role in deregulated glycolytic pathways in diseases associated with inflammation, neurodegeneration, and cancer. , As the end product of glycolysis, pyruvate might be converted into alanine via alanine transaminase (ALT) or lactate via lactate dehydrogenase (LDH), or it can enter the tricarboxylic acid cycle (TCA) via the catalysis of the pyruvate dehydrogenase complex (PDH). The metabolic conversion of [1- 13 C]­pyruvate-to-[1- 13 C]­lactate (P–L) has shown potential in clinical trials of prostate cancer patients, − and we have recently used it to produce the first mouse tumor imaging by PHIP-SAH . However, by approaching TCA, [1- 13 C]­pyruvate is converted via PDH into 13 CO 2 , thereby preventing the direct detection of downstream TCA metabolites.…”