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.

Public Health Relevance

Radiographic imaging tests are essential for tumor staging in children with cancer, but are associated with a risk of inducing secondary cancers later in life. The goal of this project is to develop a new, radiation free magnetic resonance (MR) imaging approach for whole body staging of children with cancer, based on whole body diffusion-weighted MR imaging and off-label use of the iron supplement ferumoxytol as a contrast agent for MR imaging. This new staging test could have immense significance for health care economics and patient care by providing a customized one-stop cancer staging approach for children with cancer, 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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD081123-04
Application #
9463355
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Giacoia, George
Project Start
2015-04-01
Project End
2020-03-31
Budget Start
2018-04-01
Budget End
2019-03-31
Support Year
4
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Stanford University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94304
Pourmehdi Lahiji, Arian; Jackson, Tatianie; Nejadnik, Hossein et al. (2018) Association of Tumor [18F]FDG Activity and Diffusion Restriction with Clinical Outcomes of Rhabdomyosarcomas. Mol Imaging Biol :
Muehe, Anne M; Theruvath, Ashok J; Lai, Lillian et al. (2018) How to Provide Gadolinium-Free PET/MR Cancer Staging of Children and Young Adults in Less than 1 h: the Stanford Approach. Mol Imaging Biol 20:324-335
Aghighi, Maryam; Theruvath, Ashok J; Pareek, Anuj et al. (2018) Magnetic Resonance Imaging of Tumor-Associated Macrophages: Clinical Translation. Clin Cancer Res 24:4110-4118
Bulte, Jeff W M; Daldrup-Link, Heike E (2018) Clinical Tracking of Cell Transfer and Cell Transplantation: Trials and Tribulations. Radiology 289:604-615
Daldrup-Link, Heike E (2017) Ten Things You Might Not Know about Iron Oxide Nanoparticles. Radiology 284:616-629
Li, Kai; Nejadnik, Hossein; Daldrup-Link, Heike E (2017) Next-generation superparamagnetic iron oxide nanoparticles for cancer theranostics. Drug Discov Today 22:1421-1429
Pareek, Anuj; Muehe, Anne M; Theruvath, Ashok J et al. (2017) Whole-body PET/MRI of Pediatric Patients: The Details That Matter. J Vis Exp :
Toth, Gerda B; Varallyay, Csanad G; Horvath, Andrea et al. (2017) Current and potential imaging applications of ferumoxytol for magnetic resonance imaging. Kidney Int 92:47-66
Daldrup-Link, Heike (2017) How PET/MR Can Add Value For Children With Cancer. Curr Radiol Rep 5:
Theruvath, Ashok J; Ilivitzki, Anat; Muehe, Anne et al. (2017) A PET/MR Imaging Approach for the Integrated Assessment of Chemotherapy-induced Brain, Heart, and Bone Injuries in Pediatric Cancer Survivors: A Pilot Study. Radiology 285:971-979

Showing the most recent 10 out of 16 publications