Personalized Whole Body Staging for Children with Cancer: A Solution to the Conundrum of Long-Term Side Effects from CT and PET/CT Scans

 描述(申请人提供)：全世界每年有超过17.5万名儿童被诊断出患有恶性肿瘤。CT和基于放射性示踪剂的成像测试对于这些患者的肿瘤分期是必不可少的。然而，人们已经认识到，临床上需要的放射学分期程序可能会在以后的生活中导致辐射诱发的继发性癌症。因此，迫切需要开发替代的无辐射分级测试。为了解决这一问题，本提案的总体目标是开发一种新的、无辐射的磁共振成像方法，用于儿童癌症的全身分期，并将这种新的分期测试与基于18F-FDG-PET/CT的成像测试的诊断效率和准确性进行比较。我们的MR分期检查依赖于全身弥散加权磁共振(WB-DW)成像和标签外使用铁补充阿魏酸甘油作为MR成像的造影剂。我们的团队已经证明，由氧化铁纳米颗粒组成的阿魏酸甘油可以用作磁共振造影剂，因为这些纳米颗粒在MRI上提供了可测量的T1和T2信号变化。我们假设，与基于18F-FDG-PET的成像测试相比，阿魏酸甘油酯增强的WB-DW磁共振成像将为癌症分期和再分期提供同等或更高的敏感性和特异性。我们最近获得了FDA IND的批准，开始在儿科患者中评估阿魏酸甘油酯增强的磁共振成像程序的临床试验。据我们所知，这是第一项针对儿科患者的研究，根据18F-FDG PET/CT综合扫描的概念，将用于肿瘤检测的MR成像技术(全身扩散)与用于解剖定位的MR成像技术(阿魏酸甲酯增强的T1加权图像)相结合。为了寻求一种改进的、立即适用于临床的全面一站式儿童癌症分期的成像方法，我们将首先优化我们的阿魏醇增强WB-DW磁共振成像方案，然后将这一新的分期检测与18F-FDG-PET/CT和18F-FDG-PET/MR程序的诊断价值进行比较，最后，确定与18F-FDG-PET成像检测相比，阿魏酸甘油增强的WB-DW MRI能否为肿瘤治疗疗效评估提供同等或更多的信息。因此，我们提出了一种高度创新的诊断工具，该工具应该能够解决强制性诊断分期程序和晚年继发性癌症风险的难题。通过开发这一新的成像测试，并利用FDA批准的铁补充剂作为儿童造影剂(通过标签外使用)，我们预计将根据我们儿科患者的特定需求建立定制的癌症分期方案，使大量患者从诊断分期评估中避免辐射暴露，并最终消除日后潜在的长期继发性癌症发展的相关风险。

 DESCRIPTION (provided by applicant): More than 175,000 children worldwide are diagnosed with malignant tumors every year. CT and radiotracer- based imaging tests are essential for tumor staging in these patients. However, it has been recognized that clinically needed radiographic staging procedures may cause radiation-induced secondary cancers later in life. Thus, there is an urgent need for the development of alternative radiation-free staging tests. In order to solve this problem, the overall goal of this proposal is to develop a new, radiation free MR imaging approach for whole body staging of children with cancer and to compare the diagnostic efficacy and accuracy of this new staging test with 18F-FDG-PET/CT based imaging tests. Our MR staging exam relies on whole body diffusion-weighted magnetic resonance (WB-DW MR) imaging and off-label use of the iron supplement ferumoxytol as a contrast agent for MR imaging. Our group has shown that ferumoxytol, which is composed of iron oxide nanoparticles, can be used as an MR contrast agent, as these nanoparticles provide measurable T1- and T2-signal changes on MRI. We hypothesize that ferumoxytol-enhanced WB-DW MR imaging will provide equal or improved sensitivities and specificities for cancer staging and re-staging compared to 18F-FDG-PET based imaging tests. We recently received FDA IND approval to initiate clinical trials for evaluation of ferumoxytol-enhanced MR imaging procedures in pediatric patients. To the best of our knowledge, this is the first study in pediatri patients that integrates an MR imaging technique for tumor detection (whole body diffusion) with an MR imaging technique for anatomical orientation (ferumoxytol- enhanced T1-weighted images), in accordance with the concept of integrated 18F-FDG PET/CT scans. In our pursuit of an improved and immediately clinically applicable imaging approach for comprehensive one-stop cancer staging in children, we will first optimize our imaging protocol for ferumoxytol-enhanced WB-DW MR scans, then compare the diagnostic value of this new staging test with 18F-FDG-PET/CT and 18F-FDG-PET/MR procedures and finally, determine if ferumoxytol-enhanced WB-DW MRI can provide equal or additional information for tumor therapy response assessment compared to 18F-FDG-PET based imaging tests. Thus, we propose a highly innovative diagnostic tool that should enable us to solve the conundrum of mandatory diagnostic staging procedures and concurrent risk of secondary cancer later in life. By developing this new imaging test and exploiting an FDA-approved iron supplement as a contrast agent for children via an off-label use, we anticipate to establish customized cancer staging protocols towards the specific needs of our pediatric patients, saving a large patient population from radiation exposure from diagnostic staging evaluations, and ultimately, eliminating associated risks of potential long-term secondary cancer development later in life.