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This article is part of the supplement: Abstracts of the 16th International Charles Heidelberger Symposium on Cancer Research

Open Access Oral presentation

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

Kevin M Brindle

Author Affiliations

Department of Biochemistry, University of Cambridge and Cancer Research UK Cambridge Research Institute, Cambridge, UK

BMC Proceedings 2010, 4(Suppl 2):O24  doi:10.1186/1753-6561-4-S2-O24


The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1753-6561/4/S2/O24


Published:24 September 2010

© 2010 Brindle; licensee BioMed Central Ltd.

Oral presentation

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].

References

  1. Brindle K: New approaches for imaging tumour responses to treatment.

    Nature Rev Cancer 2008, 8:1-14. Publisher Full Text OpenURL

  2. Krishnan AS, Neves AA, de Backer MM, Hu DE, Davletov B, Kettunen MI, Brindle KM: Detection of cell death in tumors using MRI and a gadolinium-based targeted contrast agent.

    Radiology 2008, 246:854-862. PubMed Abstract | Publisher Full Text OpenURL

  3. Day SE, Kettunen MI, Gallagher FA, Hu DE, Lerche M, Wolber J, Golman K, Ardenkjaer-Larsen JH, Brindle KM: Detecting tumor response to treatment using hyperpolarized 13C magnetic resonance imaging and spectroscopy.

    Nat Med 2007, 13:1382-1387. PubMed Abstract | Publisher Full Text OpenURL

  4. Witney TH, Kettunen MI, Day SE, Hu DE, Neves AA, Gallagher FA, Fulton SM, Brindle KM: A comparison between radiolabeled fluorodeoxyglucose uptake and hyperpolarized C-13-labeled pyruvate utilization as methods for detecting tumor response to treatment.

    Neoplasia 2009, 11:574-582. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  5. Gallagher FA, Kettunen MI, Hu DE, Jensen PR, Zandt RI, Karlsson M, Gisselsson A, Nelson SK, Witney TH, Bohndiek SE, Hansson G, Peitersen T, Lerche MH, Brindle KM: Production of hyperpolarized [1,4-13C)]malate from [1,4-13C)]fumarate is a marker of cell necrosis and treatment response in tumors.

    Proc Natl Acad Sci U S A 2009, 106:19801-19806. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  6. Gallagher FA, Kettunen MI, Day SE, Hu DE, Ardenkjær-Larsen JH, in 't Zandt R, Jensen PR, Karlsson M, Golman K, Lerche MH, Brindle KM: Magnetic resonance imaging of pH in vivo using hyperpolarized 13C-labeled bicarbonate.

    Nature 2008, 453:940-943. PubMed Abstract | Publisher Full Text OpenURL