Detecting tumor responses to treatment using hyperpolarized ¹³C magnetic resonance spectroscopic imaging

Patients with similar tumor types can have markedly different responses to the same therapy. The development of new treatments would benefit significantly, therefore, from the introduction of imaging methods that allow an early assessment of treatment response in individual patients, allowing rapid selection of the most effective treatment [1]. We have been developing methods for detecting the early responses of tumors to therapy. This has included a targeted MRI contrast agent for detecting tumour cell death [2] and MR imaging of tumor cell metabolism using hyperpolarized ¹³C-labelled cellular metabolites. Nuclear spin hyperpolarization techniques can increase sensitivity in the MR experiment by >10,000x. This has allowed us to image the location of labeled cell substrates and, more importantly, their metabolic conversion into other metabolites. We showed that exchange of hyperpolarized ¹³C label between lactate and pyruvate, in the reaction catalyzed by the enzyme lactate dehydrogenase, could be imaged in tumors and that this flux was decreased in treated tumors undergoing drug-induced cell death [3]. We compared this method for detecting treatment response with measurements of fluorodeoxyglucose uptake [4]. We have shown, more recently, that hyperpolarized [1,4-¹³C]fumarate can be used to detect tumor cell necrosis post treatment [5]. We have also shown that tissue pH can be imaged from the ratio of the signal intensities of hyperpolarized H¹³CO₃- and ¹³CO₂ following intravenous injection of hyperpolarized H¹³CO₃-. The technique was demonstrated with a study on a mouse tumor model, which showed that the average tumor pH was significantly lower than the surrounding tissue. Since bicarbonate is already used intravenously in humans, we propose that this technique could be used clinically to image disease and response to treatment [6].