Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA, UK.
Biochem Soc Trans. 2010 Oct;38(5):1220-4. doi: 10.1042/BST0381220.
Patients with similar tumour types frequently show different responses to the same therapy. The development of new treatments would benefit, therefore, from imaging methods that allow an early assessment of treatment response in individual patients, allowing rapid selection of the most effective treatment. We have been using (13)C MRSI (magnetic resonance spectroscopic imaging) of tumour cell metabolism, using hyperpolarized (13)C-labelled cellular metabolites, to detect treatment response. Nuclear spin hyperpolarization can increase sensitivity in the magnetic resonance experiment >10,000 times, allowing us to image labelled cell substrates in vivo and their subsequent metabolism. We showed that exchange of hyperpolarized (13)C label between lactate and pyruvate, catalysed by lactate dehydrogenase, was decreased in treated tumours undergoing drug-induced cell death, and that tissue pH could be imaged from the ratio of the signal intensities of hyperpolarized H(13)CO(3)(-) and (13)CO(2) following intravenous injection of hyperpolarized H(13)CO(3). Tumour cell glutaminase activity, a potential measure of cell proliferation, can be determined using hyperpolarized [5-(13)C]glutamine, and treatment-induced tumour cell necrosis can be imaged in vivo from measurements of the conversion of hyperpolarized [1,4-(13)C(2)]fumarate into malate. Since these substrates are endogenous and, in some cases, have already been safely infused into patients, these techniques have the potential to translate to the clinic.
患有相似肿瘤类型的患者经常对相同的治疗方法表现出不同的反应。因此，新的治疗方法的发展将受益于能够在个体患者中早期评估治疗反应的成像方法，从而能够快速选择最有效的治疗方法。我们一直在使用（13）C MRSI（磁共振波谱成像）对肿瘤细胞代谢进行研究，使用超极化（13）C 标记的细胞代谢物来检测治疗反应。核自旋超极化可以使磁共振实验的灵敏度提高>10000 倍，从而使我们能够在体内对标记的细胞底物及其随后的代谢进行成像。我们表明，在药物诱导的细胞死亡过程中，经治疗的肿瘤中由乳酸脱氢酶催化的超极化（13）C 标记物在乳酸和丙酮酸之间的交换减少，并且可以通过静脉内注射超极化 H（13）CO（3）后（13）CO（2）和 H（13）CO（3）的信号强度比来成像组织 pH 值。肿瘤细胞谷氨酰胺酶活性可以通过超极化[5-（13）C]谷氨酰胺来确定，并且可以通过测量超极化[1,4-（13）C（2）]富马酸转化为苹果酸来对体内治疗引起的肿瘤细胞坏死进行成像。由于这些底物是内源性的，并且在某些情况下已经安全地输注到患者中，因此这些技术有可能转化为临床应用。
