Brain tumors are the leading cause of death from solid tumors in children, but remain a rare disease with a prevalence of approximately 21,000 children and with 2,200 new cases diagnosed in children (<20 y) each year. Tumor staging, detecting recurrent tumor, and assessing response to therapy are critical in the treatment of brain tumors, but current imaging methods have limitations in providing such information. The objective of this study is to validate 32-deoxy-32-[F-18] fluorothymidine (18F-FLT) as an imaging agent to assess cellular proliferation in brain tumors in children and to demonstrate its utility for grading tumors at diagnosis, for accurate identification of tumor recurrence, and for early assessment of response to chemotherapy. 18F-FLT uptake in brain tumors measured by positron emission tomography (PET) will be correlated with histopathology of tumor specimens and with patient outcomes. The proposed studies will evaluate 18F-FLT-PET by testing three hypotheses: 1. 18F-FLT uptake is an accurate marker of cellular proliferation and tumor grade in central nervous system tumors in children. This hypothesis will be tested in children imaged before surgical resection of newly diagnosed central nervous system tumors. Histopathological measures of proliferation will be correlated with the 18F-FLT-PET results. 2. 18F-FLT uptake is an accurate marker cellular proliferation in children with possible recurrent central nervous system tumors. Therefore post-treatment uptake and changes in uptake during therapy may provide discrimination between recurrent tumor and benign tissue. This hypothesis will be tested in children in whom standard imaging has raised concern for tumor recurrence. 18F- FLT-PET results will be compared to histopathological measures of proliferation and to final pathological diagnosis. 3. Changes in 18F-FLT uptake demonstrate the cellular response to chemotherapy and predict clinical outcome in children receiving chemotherapy for treatment of a central nervous system tumor. To test this hypothesis, children undergoing chemotherapy for recently diagnosed central nervous system tumors will be studied by 18F-FLT-PET before chemotherapy and soon after the start (within two months) of chemotherapy. Post-therapy 18F-FLT uptake and changes in 18F-FLT uptake will be correlated with patient outcomes. Although pediatric central nervous system tumors are rare, they are a significant contributor to morbidity and mortality in children. This interdisciplinary project aims to validate and characterize the use of 18F-FLT-PET to evaluate these tumors, which, in turn, is expected improve disease management and enhance the care of children afflicted with brain tumors.

Public Health Relevance

Primary malignant tumors of the central nervous system are the most common cause of death from solid tumors in children. These tumors, however, are rare, with only 2200 new cases diagnosed each year in children in the United States, and with an estimated prevalence of approximately 21,000 cases in children and young adults. Three important issues in the treatment of pediatric brain tumors are tumor staging and grading, detecting residual/recurrent tumor, and assessing response to therapy. CT, MRI, and FDG-PET are all limited in providing this information. For example, positron emission tomography (PET) using radioactive tracers such as 18F-FDG is very useful for imaging many cancers, but is less useful in the evaluation of brain tumors due to intense uptake of 18F-FDG in normal brain tissues. Newer PET radiopharmaceuticals, such as 32-deoxy-32-[18F]fluorothymidine (18F-FLT), have the potential to improve the accuracy of medical imaging of brain tumors because their mechanism of uptake is more specific than that of 18F-FDG and there is much less uptake in the normal brain. The goals of this study are to evaluate the potential utility of PET imaging with 18F-FLT in three challenging situations in the medical management of brain tumors in children: 1) When a child presents with a new brain tumor, can 18F-FLT-PET be used to determine the aggressiveness of the tumor before surgical resection? 2) In children with suspected recurrence of a previously treated brain tumor, can 18F-FLT-PET distinguish recurrent tumor from scar tissue? 3) In children receiving chemotherapy for brain tumors, can 18F-FLT-PET be used to assess the response to therapy, which may be important in deciding whether to continue or change chemotherapy? Although pediatric central nervous system tumors are rare, they are a significant contributor to morbidity and mortality in children. This interdisciplinary project aims to validate and characterize the use of 18F-FLT-PET to evaluate these tumors, which, in turn, is expected improve disease management and enhance the care of children afflicted by this devastating illness.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01FD003718-02
Application #
8135041
Study Section
Special Emphasis Panel (ZFD1)
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Children's Hospital Boston
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02115