Detecting tumor response to treatment using hyperpolarized 13C magnetic resonance imaging and spectroscopy

Abstract

Measurements of early tumor responses to therapy have been shown, in some cases, to predict treatment outcome. We show in lymphoma-bearing mice injected intravenously with hyperpolarized [1-(13)C]pyruvate that the lactate dehydrogenase-catalyzed flux of (13)C label between the carboxyl groups of pyruvate and lactate in the tumor can be measured using (13)C magnetic resonance spectroscopy and spectroscopic imaging, and that this flux is inhibited within 24 h of chemotherapy. The reduction in the measured flux after drug treatment and the induction of tumor cell death can be explained by loss of the coenzyme NAD(H) and decreases in concentrations of lactate and enzyme in the tumors. The technique could provide a new way to assess tumor responses to treatment in the clinic.

Rapid multislice imaging of hyperpolarized 13C pyruvate and bicarbonate in the heart

“…Hyperpolarization of spins via dynamic nuclear polarization (DNP) has been explored as a method to noninvasively study real-time metabolic processes occurring in vivo using 13 C-labeled substrates (1)(2)(3). Recently, hyperpolarized 13 C pyruvate has been used to characterize cardiac metabolism noninvasively in the rat (4,5) and the pig (6).…”

“…Recently, hyperpolarized 13 C pyruvate has been used to characterize cardiac metabolism noninvasively in the rat (4,5) and the pig (6). In these studies, [1][2][3][4][5][6][7][8][9][10][11][12][13] C] pyruvate was injected intravenously, and cardiac spectra were acquired with spatial localization to the heart either by coil location or by slice selection and single-step phase encoding of the field of view.…”

“…This sequence permits whole-heart coverage (6 slices, 8.8 mm in-plane resolution) in any plane, allowing imaging of the metabolites of interest, [1][2][3][4][5][6][7][8][9][10][11][12][13] C] pyruvate, [1-13 C] lactate, and 13 C bicarbonate, within a single breathhold. Pyruvate and bicarbonate cardiac volumes were acquired, while lactate images were not acquired due to low lactate levels in the animal model studied.…”

A referenceless Nyquist ghost correction workflow for echo planar imaging of hyperpolarized [1‐13C]pyruvate and [1‐13C]lactate

“…For example, the imaging of hyperpolarized [1‐ 13 C]pyruvate and its downstream metabolic products has been used in cancer research to assess treatment response6, 7 and disease progression,8, 9 and in other tissues, such as heart10, 11 and kidney,12 to assess tissue function. The technique has now been translated to the clinic with studies in prostate cancer13 and in heart 14…”

A Hyperpolarizable 1H Magnetic Resonance Probe for Signal Detection 15 Minutes after Spin Polarization Storage

“…Nuclear spin hyperpolarization has evolved as one of most important developments in NMR and MRI in recent years as it starts finding applications in human metabolomics,1, 2, 3, 4 where their detection holds great potential to create tools for the diagnose of diseases. Among the various hyperpolarization techniques,5 dynamic nuclear polarization (DNP)6 and para‐hydrogen‐induced hyperpolarization (PHIP)7 are two of the most popular techniques.…”