# PET Biomarker for synaptic density changes after radiation therapy

> **NIH NIH R01** · CHILDREN'S HOSP OF PHILADELPHIA · 2024 · $737,118

## Abstract

Project Summary/Abstract: Whole brain synaptic density imaging with quantitative positron emission
tomography (PET) has demonstrated critical insights into understanding of neurodegenerative disorders and
epilepsy, especially in the setting of normal anatomical MRI. We propose to use quantitative whole brain PET
with a novel synaptic density tracer to characterize the synaptic density changes in the setting of targeted
radiation therapy in rodents and to correlate it to cognitive changes that occur after radiation therapy. While
radiation therapy is a life-saving standard of care for treatment of central nervous system (CNS) malignancies
in both adults and children, cognitive decline is one of the major complications and has been tied to
multifactorial mechanism which includes loss of synapses, white matter damage, endothelial cell damage, and
activation of neuroinflammatory markers within the hippocampus and pre-frontal cortex. Hippocampal sparing
radiation therapy is the leading approach to preserve cognitive function in patients requiring radiation therapy.
Unfortunately, even after hippocampal sparing radiation, over 50% of patients develop debilitating cognitive
decline. With increase in long term survival of patients with CNS malignancies, there is a critical need to
understand the mechanisms behind radiation induced brain injury, so that therapies can be targeted to prevent
post-radiation cognitive decline. Currently there are no established drugs that prevent or treat the sequelae of
radiation, nor are there biomarkers to monitor cellular damage. Availability of these could be used to modify
treatment protocols prior to the development of severe cognitive decline. Characterization of whole brain
dynamic changes in synapses and how they are related to white matter damage have not been evaluated up to
now, because tools to study whole brain synaptic density have not been readily available. To characterize the
mechanisms behind radiation induced cognitive decline, we will use a novel PET tracer that has been
established to measure synaptic density and quantitative PET modeling for quantification of synaptic density in
different regions of the human brain. We assembled a team of experts in fields of quantitative PET, rodent
quantitative MRI, rodent radiation therapy, rodent neuropathology, and cognitive assessment to determine the
time course of synaptic density changes in different regions of the brain and how it relates to pathological
assessment of synaptic density, white matter damage, and neuroinflammation. The short term goal of this
project is to characterize the hippocampal and extra-hippocampal synaptic density changes in rats after
targeted half-brain radiation. The long term goal is to use this model to characterize the molecular mechanisms
of radiation therapy induced CNS damage in human patients that must undergo radiation treatments for brain
tumors. Completion of this project will characterize a novel non-invasive biomarker of ...

## Key facts

- **NIH application ID:** 10850238
- **Project number:** 1R01CA275767-01A1
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** Mariam Aboian
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $737,118
- **Award type:** 1
- **Project period:** 2024-09-03 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10850238

## Citation

> US National Institutes of Health, RePORTER application 10850238, PET Biomarker for synaptic density changes after radiation therapy (1R01CA275767-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10850238. Licensed CC0.

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