Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA.
Britton Chance Laboratory of Redox Imaging, Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA, USA.
Adv Exp Med Biol. 2013;789:237-242. doi: 10.1007/978-1-4614-7411-1_32.
In vivo imaging/spectroscopic biomarkers for solid tumor aggressiveness are needed in the clinic to facilitate cancer diagnosis and treatment strategies. In mouse models of human melanoma and breast cancer, we were able to detect the metabolic differences among tumors of different metastatic potential and between normal and cancer tissues by optical imaging of the mitochondrial redox state of snap-frozen tissue samples. Such metabolic differences indicate that tumors of different aggressiveness have different metabolic homeostasis, which supports that kinetic parameters such as rate constant(s) can also serve as biomarkers for cancer aggressiveness and treatment response. Here we present our preliminary study on the mouse xenografts of the aggressive and indolent human breast cancer cell lines using the hyperpolarized (13)C-NMR (HP-NMR) technique. By recording the time courses of (13)C-pyruvate tracer and its metabolite signals in vivo, particularly the (13)C-lactate signal, the apparent rate constants of both the forward and reverse reactions catalyzed by lactate dehydrogenase (LDH) were extracted via the ratiometric modeling of the two-site exchange reaction that we developed. Data from four breast tumors (MCF-7, MDA-MB-468, and MDA-MB-231 medium and large) with different aggressiveness are included. We demonstrate the feasibility to quantify the apparent rate constants of LDH reactions in breast tumor xenografts.
在临床上需要用于实体瘤侵袭性的体内成像/光谱生物标志物，以促进癌症的诊断和治疗策略。在人黑色素瘤和乳腺癌的小鼠模型中，我们能够通过对冷冻组织样本的线粒体氧化还原状态进行光学成像，检测出不同转移潜能的肿瘤之间以及正常组织与肿瘤组织之间的代谢差异。这些代谢差异表明，侵袭性不同的肿瘤具有不同的代谢稳态，这表明动力学参数（如速率常数）也可以作为癌症侵袭性和治疗反应的生物标志物。在这里，我们使用 13C-NMR（HP-NMR）技术对侵袭性和惰性人乳腺癌细胞系的小鼠异种移植进行了初步研究。通过记录（13）C-丙酮酸示踪剂及其代谢物信号在体内的时间过程，特别是（13）C-乳酸信号，我们通过开发的双位点交换反应的比率模型提取了由乳酸脱氢酶（LDH）催化的正向和反向反应的表观速率常数。包含了四个具有不同侵袭性的乳腺肿瘤（MCF-7、MDA-MB-468 和 MDA-MB-231 中大和大）的数据。我们证明了在乳腺肿瘤异种移植中定量 LDH 反应的表观速率常数的可行性。
