Molecular Imaging of Cancer Cachexia

描述（由申请人提供）：癌症最未被充分探索但却具有破坏性的后果之一是恶病质，这是一种身体被紊乱的碳水化合物、脂质和蛋白质代谢所消耗的状态，这种代谢是由全身分泌的炎症细胞因子和肿瘤引起的。恶病质是所有癌症相关死亡的20-40%的原因。在3至6个月内体重下降5%与治疗效果差、疲劳和生活质量差有关，体重下降30%通常是致命的。逆转或控制这种情况的能力将对治疗结果、生活质量和死亡率产生巨大影响，但迄今为止还没有已知的治疗这种情况的方法。由于这种疾病的多因素特征，很难理解肿瘤对身体器官的影响，以及导致这种致命疾病的事件顺序。这些见解对于确定治疗策略至关重要，特别是在这十年的分子靶向药物中。了解肿瘤和正常组织之间的相互作用，以及对这种疾病的发展顺序进行无创成像的能力，对于确定这种疾病危及生命的关键阶段将是非常宝贵的。目前的多模态分子和功能成像能力为临床前模型和临床全面研究恶病质提供了独特的机会。在这个探索性应用中，我们将使用最先进的成像技术结合分子表征来了解癌症诱导的恶病质和临床前模型中的恶病质级联。在这些临床前研究中确定的影像学指标可以在未来转化为检测患者恶病质级联的发展。根据确定的代谢靶点，图像引导的siRNA递送可以在未来的研究中用于下调途径并了解它们对恶病质级联的影响。公共卫生相关性：由癌症引起的恶病质是最未被充分探索的癌症后果之一，也是所有癌症相关死亡的20-40%的原因。恶病质诱导的体重在3至6个月内下降5%与治疗效果差、疲劳和生活质量差有关，体重下降30%通常是致命的。逆转或控制这种情况的能力将对治疗结果、生活质量和死亡率产生巨大影响，但迄今为止还没有已知的治疗这种情况的方法。在这个探索性的应用中，我们将使用最先进的成像技术结合分子表征来了解癌症诱导的恶病质和恶病质级联在临床前肿瘤模型中。

DESCRIPTION (provided by applicant): One of the most under explored and yet devastating consequences of cancer is cachexia, a condition in which the body is consumed by deranged carbohydrate, lipid and protein metabolism induced by inflammatory cytokines secreted systemically, and by the tumor. Cachexia is the cause for 20-40% of all cancer related deaths. A weight loss of 5% over 3 to 6 months is associated with poor treatment outcome, fatigue and poor quality of life, and a weight loss of 30% is frequently lethal. The ability to reverse or control this condition would have a tremendous impact on treatment outcome, quality of life, and mortality, but to date there are no known cures for this condition. Because of the multi-factorial characteristics of this condition, it has been difficult to understand the impact of the tumor on body organs, and the sequence of events that leads to this lethal condition. Such insights are critically important in identifying therapeutic strategies, especially in this decade of molecular targeted medicine. The ability to understand the interaction between the tumor and normal tissues and noninvasively image the sequence of development of this condition would be invaluable in identifying critical stages when the condition becomes life-threatening. Current multi-modality molecular and functional imaging capabilities provide unique opportunities to study cachexia holistically in preclinical models and clinically. In this exploratory application, we will use state-of-the art imaging techniques in combination with molecular characterization to understand cancer-induced cachexia and the cachexia cascade in preclinical models. Imaging indices identified in these preclinical studies can, in the future, be translated to detect the development of the cachexia cascade in patients. Depending on the metabolic targets identified, image-guided siRNA delivery can be used in future studies to down-regulate pathways and understand their impact on the cachexia cascade. PUBLIC HEALTH RELEVANCE: Cachexia induced by cancer is one of the most under explored and yet devastating consequences of cancer, and is the cause for 20-40% of all cancer related deaths. Cachexia-induced weight loss of 5% over 3 to 6 months is associated with poor treatment outcome, fatigue and poor quality of life, and a weight loss of 30% is frequently lethal. The ability to reverse or control this condition would have a tremendous impact on treatment outcome, quality of life, and mortality, but to date there are no known cures for this condition. In this exploratory application, we will use state-of-the art imaging techniques in combination with molecular characterization to understand cancer-induced cachexia and the cachexia cascade in preclinical tumor models.