# Improved Radiation Therapy of Hypoxic Tumor Regions by Integrated PET, EPR, and MR Imaging  - Resubmission 01 - Revision - 1

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2021 · $403,448

## Abstract

Abstract
A number of hypoxic processes have been pathologically correlated with the development of amyloid plaque in
Alzheimers's disease (AD). Nonetheless the local development of amyloid-b plaque (Ab) has not been
successfully correlated with local brain hypoxia. We argue that the importance of registration of hypoxic loci in
the brain with location of the development of Ab will enable the precise evaluation of the response of clinical
intervention to mitigate hypoxic loci in the mitigation of the AD process. Our funded research grant R01
CA236385, as outlined in its abstract above, is to improve PET hypoxia imaging using 18F-Misonidazole
(FMISO) in localizing radiation resistant hypoxic tumor regions incorporating two clinically available MRI
modalities: dynamic contrast enhanced MRI (DCE-MRI) and Iopamidol chemical exchange saturation transfer
MRI (ICEST-MRI). The gold standard for the detection of tumor regions with low pO2, i.e., hypoxic, is electron
paramagnetic resonance pO2 imaging (EPRpO2 imaging). This supplement availability announcement NOT-
AD-20-034 as part of the general supplement fundung opportunity announcement PA-18-591 provides a
unique opportunity for expanding the application of imaging local hypoxia from cancer resistance to a second,
quite distinct and generally crucial health problem: Alzeheimer's Disease (AD). The development of a
preclinical imaging methodology to screen interventions that modulate local cerebral hypoxia may provide
breakthrough information that will inform the mitigation of AD. We propose to use a novel technology to inject
via an intraparenchymal route mesoporous silica nanotubes (MSNs) encapsulating the quantitative EPRpO2
sensor which we recently published to image local pO2. This will overcome the blood brain barrier exclusion of
the triacid EPRpO2 sensor. The work will use 18F labeled NAV4694 to locate Aβ in the brain of both C57BL/6
control and APP/PS1 AD mouse models. We will correlate the location of this biomarker of AD with locations of
low pO2 in the mouse brain. Additional PET images of the distribution of the hypoxia marker FMISO and DCE-
MRI for measuring perfusion and ICEST-MRI for assessing tissue pH will be obtained. The MRIs will be used
to correct the FMISO PET images to better agree with the EPRpO2 image, leading to a novel algorithm for
using clinical imaging approaches of FMISO PET and DCE-MRI and CEST-MRI methods in human subjects to
locate hypoxia in the brains of AD and related dementia patients and determine if mitigation of this hypoxia can
mitigate the AD process.

## Key facts

- **NIH application ID:** 10289582
- **Project number:** 3R01CA236385-02S1
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Chin-Tu Chen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $403,448
- **Award type:** 3
- **Project period:** 2020-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10289582

## Citation

> US National Institutes of Health, RePORTER application 10289582, Improved Radiation Therapy of Hypoxic Tumor Regions by Integrated PET, EPR, and MR Imaging  - Resubmission 01 - Revision - 1 (3R01CA236385-02S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10289582. Licensed CC0.

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