Day Sam E, Kettunen Mikko I, Gallagher Ferdia A, Hu De-En, Lerche Mathilde, Wolber Jan, Golman Klaes, Ardenkjaer-Larsen Jan Henrik, Brindle Kevin M
Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
Nat Med. 2007 Nov;13(11):1382-7. doi: 10.1038/nm1650. Epub 2007 Oct 28.
Measurements of early tumor responses to therapy have been shown, in some cases, to predict treatment outcome. We show in lymphoma-bearing mice injected intravenously with hyperpolarized [1-(13)C]pyruvate that the lactate dehydrogenase-catalyzed flux of (13)C label between the carboxyl groups of pyruvate and lactate in the tumor can be measured using (13)C magnetic resonance spectroscopy and spectroscopic imaging, and that this flux is inhibited within 24 h of chemotherapy. The reduction in the measured flux after drug treatment and the induction of tumor cell death can be explained by loss of the coenzyme NAD(H) and decreases in concentrations of lactate and enzyme in the tumors. The technique could provide a new way to assess tumor responses to treatment in the clinic.
在某些情况下,已证明对早期肿瘤治疗反应的测量可预测治疗结果。我们在静脉注射超极化[1-(13)C]丙酮酸的荷淋巴瘤小鼠中发现,使用(13)C磁共振波谱和波谱成像可测量肿瘤中乳酸脱氢酶催化的(13)C标记在丙酮酸和乳酸羧基之间的通量,且该通量在化疗后24小时内受到抑制。药物治疗后测量通量的降低以及肿瘤细胞死亡的诱导可通过辅酶NAD(H)的丧失以及肿瘤中乳酸和酶浓度的降低来解释。该技术可为临床评估肿瘤对治疗的反应提供一种新方法。