# Lung Functional Avoidance Radiotherapy Using Hyperpolarized Xenon MRI

> **NIH NIH R01** · XEMED, LLC · 2024 · $674,175

## Abstract

SUMMARY
Customized 3D planning of radiation therapy for lung cancer delivers a lethal dose to the tumor
region while avoiding important structures (spine) and organs (esophagus, heart, lungs) Since
radiation dose to functioning lung is associated with acute radiation pneumonitis and chronic
radiation fibrosis, researchers seek to shift dosage preferentially away from lung regions with
highest function. Several lung functional imaging modalities have been investigated (ventilation-
perfusion SPECT and PET, 4DCT, hyperpolarized 3He). These studies indicate that regional
ventilation is not the optimal biomarker. What is needed is a high-resolution imaging modality,
tolerable to patients who have difficulty holding their breath, that delineates regions of full lung
function warranting preservation, and also identifies regions whose function is irrevocably gone.
Hyperpolarized xenon-129 (HXe) MRI provides highly detailed maps of several lung functional
characteristics. Its solubility in tissues and affinity for hemoglobin allow it to be used as a tracer
for gas exchange kinetics, a so-called “regional DLCO”. Up until now, HXe imaging modalities
required long breath holds, which are not well tolerated by lung-compromised patients. We
developed an HXe assessment technique that probes several lung function characteristics,
including gas exchange to/from red blood cells, with a natural tidal-breathing protocol. Our
industrial team developed an automated xenon hyperpolarizer that delivers the required multi-liter
volumes at polarizations that approach 50%, enabling this protocol to become routine.
We propose a translational study applying HXe MRI to functional avoidance plan optimization to
minimize fibrosis in lung cancer patients. To maximize statistical significance, we stratify the
patient cohort selecting patients with significant heterogeneity: half with de novo lung cancer with
GOLD stage 3+ emphysema comorbidity and half receiving RT for their second (primary) lung
cancer. Maps will delineate three functional regions: full function with both ventilation and gas
exchange to RBCs (extra importance for avoidance), regions where function is irrevocably absent
(reduced avoidance), and other regions where function may be present or recoverable (normal
avoidance). In year 1 we conduct an open-label trial to optimize the functional imaging protocols
with upgraded hardware. With IRB and DSMB approval, our Phase 2 clinical trial will enroll 70
patients: half receiving standard-of-care treatment and half undergoing RT guided by HXe MRI.
Six-month post-treatment assessments include changes in HXe MRI, for regional correlation with
local dose. Primary endpoint will be change in DLCO, with secondary endpoints of breathing-
related quality of life change from baseline, spirometry/DLCO relative to predicted,
incidence/severity of pneumonitis, and change in HXe-MRI.

## Key facts

- **NIH application ID:** 10693958
- **Project number:** 5R01CA255434-03
- **Recipient organization:** XEMED, LLC
- **Principal Investigator:** STEPHEN J KADLECEK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $674,175
- **Award type:** 5
- **Project period:** 2021-09-17 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10693958

## Citation

> US National Institutes of Health, RePORTER application 10693958, Lung Functional Avoidance Radiotherapy Using Hyperpolarized Xenon MRI (5R01CA255434-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10693958. Licensed CC0.

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