Effects of fasting on serial measurements of hyperpolarized [1‐ ¹³ C]pyruvate metabolism in tumors

Abstract

Imaging of the metabolism of hyperpolarized [1‐13C]pyruvate has shown considerable promise in preclinical studies in oncology, particularly for the assessment of early treatment response. The repeatability of measurements of 13C label exchange between pyruvate and lactate was determined in a murine lymphoma model in fasted and non‐fasted animals. The fasted state showed lower intra‐individual variability, although the [1‐13C]lactate/[1‐13C]pyruvate signal ratio was significantly greater in fasted than in non‐fasted mice, which may be explained by the higher tumor lactate concentrations in fasted animals. These results indicate that the fasted state may be preferable for the measurement of 13C label exchange between pyruvate and lactate, as it reduces the variability and therefore should make it easier to detect the effects of therapy. © 2016 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.

Analysis of 13C and 14C labeling in pyruvate and lactate in tumor and blood of lymphoma‐bearing mice injected with 13C‐ and 14C‐labeled pyruvate

“…Tumors were established by subcutaneous inoculation of a suspension of 5 × 10 6 viable EL4 murine lymphoma cells (in a volume of 100 μL) in the left flank of C57BL/6 mice (Charles River Ltd., Harlow, Essex, UK) ( n = 69) at 6–8 weeks of age, when the animals were ~20 g. Studies were performed when the tumors had grown to a size of ~2 cm 3 , which was typically 10 days following implantation. Animals, which were not submitted to any dietary restriction, were anesthetized by either inhalation of 1–2% isoflurane (Isoflo, Abbotts Laboratories Ltd., Maidenhead, Berkshire, UK) in air/O 2 (75%/25%, 2 L/min) or by intraperitoneal administration of 10 mL/kg body weight of a 5: 4: 31 mixture of Hypnorm (VetaPharma, Sherburn‐in‐Elmet, Leeds, North Yorkshire, UK), Hypnovel (Roche, Welwyn Garden City, Hertfordshire, UK) and saline ( n = 5). Body temperature was maintained by blowing warm air through the magnet bore.…”

Hyperpolarized 13C spectroscopic imaging using single‐shot 3D sequences with unpaired adiabatic refocusing pulses

“…Tumors were obtained by subcutaneous implantation of EL4 murine lymphoma cells, as described in Reference . Mice were fasted for 6–8 h before imaging . Images were acquired at 7 T and the [1‐ 13 C] pyruvate was hyperpolarized as described previously .…”

Increased hyperpolarized [1‐13C] lactate production in a model of joint inflammation is not accompanied by tissue acidosis as assessed using hyperpolarized 13C‐labelled bicarbonate

“…A reference FSE proton image was acquired as a single axial slice (6‐10 mm thick) that encompassed both feet including the heel, up to where the top of the talus meets the leg. [1‐ 13 C]pyruvate (99% 13 C labelled, 44 mg) in a solution containing 15 mmol/l of trityl radical, tris(8‐carboxy‐2,2,6,6‐tetra(hydroxyethyl)‐benzo‐(1‐5)‐bis‐(1,3)‐dithiole‐4‐yl)‐methyl sodium salt (OX063; GE Healthcare, Amersham, UK) and 1.5 mmol/l gadolinium chelate (Dotarem, Guerbet, Paris, France) was polarized as described previously43 using a Hypersense dynamic nuclear polarization (DNP) system (Oxford BioTools, Abingdon, UK). The sample was dissolved in superheated (180°C, ~10 bar) buffer (40 mM 4‐(2‐hydroxyethyl)‐1‐piperazine‐ethanesulfonic acid (HEPES), 94 mM NaOH, 30 mM NaCl and 50 mg/l ethylenediaminetetraacetic acid (EDTA)) to give a final pyruvate concentration of 0.82 M, 200 μl of which was injected via a tail vein.…”