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

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 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.