Figure 1

Hyperpolarised [1-¹³C]pyruvate and a model of cancer metastasis to the brain. (A) Three weeks after model induction via IC injection, the presence of blood-brain barrier disruption is visible via gadolinium enhanced T1 weighted MRI, shown prior to (i) and post (ii) gadolinium administration, with the difference clearly revealing the region of disease (iii). The two spectroscopic slices chosen are additionally shown; scale bar 20 mm. (B) Representative ipsilateral spectrum acquired from the region of disease, with lactate, pyruvate hydrate, alanine and bicarbonate visible following the infusion of hyperpolarised [1-¹³C]pyruvate. (C) Immunohistochemical staining of the tumour in (A) reveals the presence of disease near the injection site, (i) here occupying approximately a 3.6 mm³ area within the striatum. (ii) Cells with a metastatic phenotype can be seen growing along the perivascular niche, which express (iii) TNF receptor I along the inside of the capillary bed in the region of disease (arrow; brown). (D) Despite the histologically-confirmed presence of disease, we did not detect a significant difference in the lactate-to-pyruvate ratio at any time points between the affected and control hemispheres of the brain although the ratio decreased over time. TNF administration likewise did not significantly alter the lactate-to-pyruvate ratio observed. (E) After fitting to a pseudo-first-order kinetic model, we found that the observed lactate/pyruvate ratio correlated significantly and positively with the returned rate constant (Spearman’s ρ ≈ 0.9; regression line shown). (F) In contrast to previously published work, and our expectations, we did not observe any significant correlation of apparent lactate production with tumour volume. (G) In culture, however the ENU-1564 cell line injected was highly glycolytic and comparable to other reported highly glycolytic cell lines.