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

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2022 · $622,673

## Abstract

Hypoxic resistance to radiation therapy has been known for over a century. However, effective image-guided
approaches to target resistant hypoxic tumor regions have been lacking. A recent publication of the results
from a Phase II clinical trial in France indicates that positron emission tomography (PET) using 18F-fluoro-
misonidazole (FMISO) to define region-of-interest (ROI) for hypoxic tumor targeting was shown to fail in
improving tumor control and treatment outcome. The long-term objective of this proposed research project is to
develop novel integrated multi-modality imaging approaches to effectively guide radiation delivery for
significantly improving therapy precision and treatment outcome of resistant hypoxic tumor regions. Our recent
work in animal studies using electron paramagnetic resonance (EPR) images (EPRI) of absolute pO2 has
demonstrated that targeting the hypoxic regions of tumors with extra radiation dose (i.e., boost in dose
painting) increases tumor cure. This involved novel 3D rapidly printed radiation blocks and conformal animal
radiation. We showed improved tumor cure by comparing uniform radiation delivery of the dose to all tumors
sufficient to cure 15% of tumors (determined in separate experiments) and then randomized to receive extra
doses of radiation to either (1) all hypoxic tumor volumes determined by the EPR pO2 image (pO2 < 10 torr) or
(2) equal volume dose boosts to better-oxygenated tumor. The results showed that treatment (1) offered a
significantly better outcome, including sparing critical organs from damage caused by high dose radiation. This
demonstrates that EPR pO2 images have the potential to guide improved radiation therapy of hypoxic tumors.
Unfortunately, EPR images are currently not available for routine uses in clinical practice. We hypothesize that
using EPRI pO2 images as the gold standard, novel quantitative hypoxia parametric imaging methodologies
based on PET-FMISO data can be established, incorporating consideration and correlation of data from other
clinically available hypoxia-related imaging methods such as dynamic contrast enhanced magnetic resonance
imaging (DCE-MRI) and Iodopamidol diamagnetic chemical exchange saturation transfer (Idia-CEST or
ICEST) pH MRI. These clinically available MRI studies will sharpen the hypoxic tumor region definition for
more effective radiation boost delivery in improving treatment outcomes. We will initially pursue the following
specific aims in animal studies: (1) Implementing and validating novel quantitative multi-modality PET/MR/EPR
imaging methodologies; (2) Developing statistical methodologies for deriving modified parametric images by
integrating multi-modality PET and MRI data in order to emulate EPR images; (3) Employing the established
methods developed in Aim (2) for validation in delivering improved precision radiotherapy of hypoxic tumors to
achieve better treatment outcomes using multi-modality parametric imaging.

## Key facts

- **NIH application ID:** 10314063
- **Project number:** 5R01CA236385-03
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Chin-Tu Chen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $622,673
- **Award type:** 5
- **Project period:** 2020-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10314063

## Citation

> US National Institutes of Health, RePORTER application 10314063, Improved Radiation Therapy of Hypoxic Tumor Regions by Integrated PET, EPR, and MR Imaging  - Resubmission 01 (5R01CA236385-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10314063. Licensed CC0.

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