JHU ICMIC Program, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Cancer Res. 2011 Nov 15;71(22):6948-56. doi: 10.1158/0008-5472.CAN-11-1095. Epub 2011 Sep 26.
Cancer-induced cachexia is a complex and poorly understood life-threatening syndrome that is characterized by progressive weight loss due to metabolic alterations, depletion of lipid stores, and severe loss of skeletal muscle protein. Gaining the ability to noninvasively image the presence or onset of cachexia is important to better treat this condition, to improve the design and optimization of therapeutic strategies, and to detect the responses to such treatments. In this study, we employed noninvasive magnetic resonance spectroscopic imaging (MRSI) and [(18)F]fluoro-2-deoxy-D-glucose ((18)FDG) positron emission tomography (PET) to identify metabolic signatures typical of cachectic tumors, using this information to analyze the types and extents of metabolic changes induced by the onset of cachexia in normal tissues. Cachexia was confirmed by weight loss as well as analyses of muscle tissue and serum. In vivo, cachexia-inducing murine adenocarcinoma (MAC)16 tumors were characterized by higher total choline (tCho) and higher (18)FDG uptake than histologically similar noncachectic MAC13 tumors. A profound depletion of the lipid signal was observed in normal tissue of MAC16 tumor-bearing mice but not within the tumor tissue itself. High-resolution (1)H magnetic resonance spectroscopy (MRS) confirmed the high tCho level observed in cachectic tumors that occurred because of an increase of free choline and phosphocholine. Higher succinate and lower creatine levels were also detected in cachectic tumors. Taken together, these findings enhance our understanding of the effect of cancer on host organs and tissues as well as promote the development of noninvasive biomarkers for the presence of cachexia and identification of new therapeutic targets.
癌症恶病质是一种复杂且尚未被充分理解的危及生命的综合征，其特征是由于代谢改变、脂质储存减少和骨骼肌蛋白严重丢失导致进行性体重减轻。能够无创性地成像恶病质的存在或发生对于更好地治疗这种疾病、改善治疗策略的设计和优化以及检测对这些治疗的反应非常重要。在这项研究中，我们使用非侵入性磁共振光谱成像（MRSI）和 [(18)F]氟-2-脱氧-D-葡萄糖 ((18)FDG)正电子发射断层扫描（PET）来识别恶病质肿瘤的典型代谢特征，利用这些信息来分析正常组织中恶病质发生引起的代谢变化的类型和程度。通过体重减轻以及肌肉组织和血清分析来确认恶病质。在体内，恶病质诱导的鼠腺癌（MAC）16 肿瘤的总胆碱（tCho）和 [(18)FDG]摄取均高于组织学上相似的非恶病质 MAC13 肿瘤。在 MAC16 肿瘤荷瘤小鼠的正常组织中观察到脂质信号明显减少，但肿瘤组织本身没有这种情况。高分辨率（1）H 磁共振波谱（MRS）证实了在恶病质肿瘤中观察到的高 tCho 水平，这是由于游离胆碱和磷酸胆碱的增加所致。还检测到恶病质肿瘤中琥珀酸盐升高和肌酸水平降低。总之，这些发现增强了我们对癌症对宿主器官和组织的影响的理解，并促进了非侵入性生物标志物的发展，用于恶病质的存在和识别新的治疗靶点。
