# Development of Novel Heterogeneous Range Modulators for FLASH Particle Therapy

> **NIH NIH R21** · UNIVERSITY OF PENNSYLVANIA · 2024 · $403,219

## Abstract

FLASH radiotherapy utilizing ultra-high dose rate has the potential of being a substantial evolutionary
advancement for cancer treatment. Ultra-high dose rate radiation provides a benefit of decreased normal
tissue toxicities while maintaining equivalent tumor killing effect. Among different modalities, particle therapy
has been an active area of research to integrate its unique characteristics with the FLASH effect because
proton therapy remains the only clinically assessable modality that can potentially treat deep seated tumors
under FLASH conditions. Thus, developing methods to enable FLASH proton therapy with clinically available
accelerators is an important step to both unravel the biological mechanism using preclinical studies, clinical
trials as well as explore the physical hardware requirements for clinical implementation.
 In FLASH proton therapy, beam modulation devices are important accessories for enabling ultra-fast
dose delivery based on the clinically available cyclotrons and synchrocyclotron systems. These work by
transforming an ultra-high dose rate mono-energetic proton pencil to a multi-energy spot after passing through
varying thicknesses of modulating material. In this way, a multi-energy layer pencil beam scanning proton plan
can be delivered completely in less than a second without the need for beam pausing for energy switching.
The most common modulator is the ridge filter, which consists of uniform density spikes of varying height. The
limitation of this design includes restricted structure stability and modulation flexibility.
We propose to develop a new class of heterogeneous density range modulators based on the novel
PixelPrint technology, to facilitate FLASH therapy. By continuously varying the ratio of filament to air, PixelPrint
technology is capable of 3D printing phantoms with voxel-wise heterogeneous density. By utilizing material
density as an optimization parameter, the new devices will have robust structure and high flexibility in
modulation. The hypothesis is that the 3D printed heterogeneous density modulator degrades the beam
energy across the transverse plane of the particle beam, based on both local material density and the
stopping power distribution of the material. With greater flexibility compared to current binary modulation
only design, complex modulation is achievable for application in universal range modulator and patient-specific
modulators. Our deliverables will include design methods to optimize density structures for range modulation,
and experimentally validated modulators for proton FLASH therapy applications. The specific aims are:
Aim 1. Development of density optimization algorithms for range modulation.
Aim 2. Experimental validation and characterization of 3D printed heterogeneous range modulators.
Aim 3. Development of patient-specific modulators for Proton FLASH therapy.
If successful, the approach will enable a new class of range modulators to enable FLASH particle therapy with
fl...

## Key facts

- **NIH application ID:** 10952781
- **Project number:** 1R21CA294634-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Boon-Keng Kevin Teo
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $403,219
- **Award type:** 1
- **Project period:** 2024-06-07 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10952781

## Citation

> US National Institutes of Health, RePORTER application 10952781, Development of Novel Heterogeneous Range Modulators for FLASH Particle Therapy (1R21CA294634-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10952781. Licensed CC0.

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