# Correcting [18]F-Misonidazole PET with MRI and EPR to improve hypoxia-guided radiation therapy

> **NIH NIH F31** · UNIVERSITY OF CHICAGO · 2021 · $46,036

## Abstract

Project Summary
 In this project, we propose to correct [18]F-Misonidazole (FMISO) Positron Emission Tomography (PET)
images to make PET be more accurate in measuring hypoxia. Hypoxia - a deficiency in oxygen - is a strong
promotor of tumor radioresistance, yet there are no established clinical methods to accurately image oxygenation
in vivo to improve treatment. Preclinical studies that acquired pO2 measurements using electron paramagnetic
resonance (EPR) imaging have shown that targeting hypoxic tumor sub-regions with a boost of TCD95 after
irradiating the whole tumor with TCD15, significantly increased tumor control when compared to the boosting
normoxic tumor sub-regions with TCD95. So far this has been demonstrated in fibrosarcoma (p = 0.04) and
mammary carcinoma (p = 0.013) tumor types. This shows that if hypoxic tumor sub-regions can be
accurately imaged and targeted with a boosted dose – better known as dose painting – the overall dose
deposition to surrounding healthy tissues can be decreased while improving tumor control.
 In recent years, clinical trials have used FMISO PET for radiation therapy dose plans with the hypothesis that
targeting hypoxic tumor regions with a boost of radiation, as defined by FMISO uptake, would increase survival.
These trials did not, however, show improvement when compared to treatment plans with and without a boost
of radiation. These outcomes are in direct contrast to the EPR hypoxia studies previously mentioned. We
hypothesize this is due to the imperfect binding mechanisms of FMISO to hypoxic cells, as well as general
limitations of PET tracers being unable to reach hypoxic tumor regions due to their chaotic vasculature or
acidosis. In response to the failure of using only FMISO PET to target hypoxia, we propose to include anatomical
and physiological information of tumor vasculature and pH imaged with Dynamic Contrast Enhanced (DCE) MRI
and chemical exchange saturation transfer (CEST) MRI, respectively. DCE-MRI and CEST-MRI will be used to
correct the PET image to show hypoxic tumor regions, using EPR as the ground truth of hypoxia.
 The specific aims of the proposal are to develop and execute a study design to (1) evaluate discrepancies
between tumor hypoxia regions as defined by FMISO PET and EPR, (2) identify tumor features in DCE-MRI and
CEST-MRI that result in poor overlap between hypoxia as defined by PET and EPR, and (3) develop a correction
PET/MRI algorithm to improve PET measurement of hypoxia, using EPR hypoxia measurements as the gold
standard. Upon completion, aim 1 will demonstrate the need for correcting FMISO PET images. Aim 2 will identify
correlations between vascular permeability and pH features and low or high PET uptake, where it might not
match with hypoxia as defined by EPR. The third aim will take those features to create a decision tree algorithm
to correct FMISO PET definition of hypoxia. We intend for this PET/MRI correction algorithm to eventually be
implemented in clinical ...

## Key facts

- **NIH application ID:** 10234423
- **Project number:** 1F31CA254223-01A1
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Inna Gertsenshteyn
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,036
- **Award type:** 1
- **Project period:** 2021-04-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10234423

## Citation

> US National Institutes of Health, RePORTER application 10234423, Correcting [18]F-Misonidazole PET with MRI and EPR to improve hypoxia-guided radiation therapy (1F31CA254223-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10234423. Licensed CC0.

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