A novel imaging biomarker for detecting treatment response in high-grade glioma

最常见的脑癌，胶质母细胞瘤，预后极差，诊断后的平均预期寿命为15个月。这种不良预后反映了这种癌症的侵袭性，也反映了它在治疗后表现的变化方式。病人对同样的治疗可能表现出明显不同的反应。新的治疗方法需要被开发出来并迅速应用于临床。这些新疗法的发展将受益于影像学方法的引入，影像学方法可以更早地评估治疗反应，这将使临床医生能够更好、更快地选择最有效的治疗方法。目前的成像技术只允许我们评估肿瘤的大小，然而，这并不理想，因为在有效治疗后，肿瘤可能需要几周甚至几个月的时间才能缩小。在某些情况下，尽管对治疗有积极反应，肿瘤甚至可能增大。治疗后肿瘤代谢的变化比肿瘤大小的变化更早。然而，在临床上使用最广泛的代谢成像技术，PET测量放射性葡萄糖类似物的摄取，在脑肿瘤中是无效的，因为肿瘤周围正常脑组织的摄取很高。这个研究项目的目的是开发一种新的成像方法，使用一种非放射性示踪剂，称为氘，可以用核磁共振成像成像。这种方法使用氘标记的葡萄糖，并测量其转化为另一种代谢物乳酸的情况，乳酸不会在正常大脑中积累。我们将在这种疾病的大鼠模型中测试这种成像技术，这种模型是通过将患者的肿瘤细胞植入其大脑而产生的。我们将使用这种新的成像技术来监测这些肿瘤的生长，然后观察它们对当前标准治疗和新治疗的反应。潜在的应用和益处如果成功，这项研究将对患者和临床医生有益。1. 患者将受益于早期诊断和检测他们的癌症对治疗的反应。我们希望这将导致发病率和死亡率的降低和生存率的提高。2. 临床医生将受益于对治疗的早期反应检测，从而及时选择最合适的治疗方案。这对医疗保健系统和患者的福利都有相关的成本效益。3. 制药公司将能够更好地评估其新药的功效。目前开发一种新药并将其推向市场的估计数字是5亿美元。这种成像方式可以简化药物开发过程，从而降低医疗保健系统的药物成本。

The most common brain cancer, glioblastoma, has an extremely poor prognosis, with a median life expectancy of 15 months from diagnosis. This poor prognosis reflects the aggressive nature of this cancer and also the variable way in which it behaves following treatment. Patients can show markedly different responses to the same treatment. New treatments need to be developed and introduced into the clinic quickly. The development of these new treatments would benefit from the introduction of imaging methods that allow an earlier assessment of treatment response, which would allow clinicians to better and more quickly select the most effective treatment. Current imaging techniques only allow us to assess the size of a tumour, however, this is not ideal as it may take several weeks or even months for a tumour to decrease in size following an effective treatment. In some cases a tumour may even increase in size despite a positive response to the treatment. Tumour metabolism can show an earlier change following treatment than tumour size. However, the most widely used metabolic imaging technique in the clinic, PET measurements of the uptake of a radioactive glucose analog, are ineffective in brain tumours because of the high uptake in the normal brain tissue surrounding the tumour. The aim of this research project is to develop a new imaging method that uses a non-radioactive tracer, known as deuterium, which can be imaged with MRI. With this method deuterium-labelled glucose is used and its conversion to another metabolite, lactate, is measured, which does not accumulate in normal brain. We will test this imaging technique in rat models of the disease, which are created by implanting patient's tumour cells into their brains. We will use this new imaging technique to monitor the growth of these tumours and then their response to the current standard-of-care treatment, as well as a new treatment. Potential applications and benefits If successful, this research could be beneficial for patients and clinicians. 1. Patients will benefit from earlier diagnosis and detection of their cancer's response to treatment. We hope this will lead to a reduction in morbidity and mortality and an increase in survival. 2. Clinicians will benefit from detection of early response to treatment allowing for timely selection of the most appropriate treatment regime. This has associated cost benefits for the healthcare system and welfare benefits for the patients. 3. Pharmaceutical companies will be able to better assess the efficacy of their new drugs. The current estimated figure for developing a new medicine and bringing it to market is $500 million. This imaging modality may allow a more streamlined drug development process, which could bring down the cost of drugs for the healthcare system.