03/24/2025
By Toby Morris
The Kennedy College of Science, Department of Physics, invites you to a Doctoral Dissertation defense by Toby Morris titled, "Novel Methods for Radiation Therapy: Theranostic Nanoparticles and FLASH Beam Monitoring."
Date: Friday, March 28, 2025
Time: 10:30 a.m. to 12:30 p.m.
Location: Olney Hall, Room 218
For Zoom Link: Please contact Toby_Morris@student.uml.edu
Advisors:
Romy Guthier, Department of Physics and Applied Physics, UMass Lowell
Ross Berbeco, Department of Radiation Oncology, Brigham and Women’s Hospital, Dana-Farber Cancer Institute and Harvard Medical School
Committee Member:
Marian Jandel, Department of Physics and Applied Physics, UMass Lowell
Abstract:
The advancement of novel methods in radiation therapy is essential for improving treatment efficacy and patient outcomes. AGuIX-Bi, a next-generation theranostic nanoparticle, enhances radiation dose amplification by replacing 70% of gadolinium (Gd) with bismuth (Bi), while maintaining MRI contrast. Its therapeutic efficacy and imaging capability were evaluated in NSCLC models under clinically relevant conditions using megavoltage (MV) irradiation and 3T MRI, as well as an SBRT-like fractionated treatment regime. In MV irradiation studies, AGuIX-Bi significantly delayed tumor growth compared to AGuIX and saline groups, while MRI assessments showed that AGuIX-Bi maintained contrast-to-noise ratios suitable for imaging. Under a multiple-injection, multiple-irradiation protocol, tumor concentrations of AGuIX-Bi increased over successive doses, enhancing tumor control compared to single-injection treatments.
Additionally, the safe clinical translation of ultra-high dose rate (UHDR) therapies, such as FLASH radiotherapy, requires precise beam monitoring. Two self-powered detectors, HEC3 and S4, were evaluated for their ability to measure individual electron-FLASH pulses at repetition rates of 60 and 360 Hz. The HEC3 detector demonstrated linear response with dose, MU, number of pulses and dose rates up to 850 Gy/s, making it suitable for high-dose and UHDR beam monitoring. The S4 detector, while lacking dose rate independence, showed promise for spatial beam profiling and steering.
AGuIX-Bi demonstrated superior tumor control compared to AGuIX, maintaining MRI contrast at 3T while proving effective in fractionated SBRT-like treatment regimens. Its accumulation at tumor sites increased with multiple injections, supporting its potential for improved radiation effect enhancement. Meanwhile, the HEC3 and S4 detectors successfully recorded FLASH pulses, confirming their capability for UHDR beam monitoring. Future efforts should focus on identifying mechanisms of action and clinically translatable dosing strategies for AGuIX-Bi, as well as advancing beam monitoring technology by integrating HEC3’s internal structure with S4’s spatial profiling capabilities, enabling comprehensive real-time monitoring of UHDR beams. These advancements pave the way for more precise, effective and personalized radiation therapy.