1144 - Enabling Continuous Monitoring of ²²⁵Ac-Based Targeted Alpha Therapy Biodistribution via Energy Calibration of a Wearable ?-Spectrometer

Purpose/Objective(s): Targeted alpha therapy (TAT) with ²²⁵Ac shows promise for treating prostate and neuroendocrine cancers but is susceptible to recoiled daughter radionuclides depositing radiation in organs-at-risk (OARs). Since the photon energy peaks of ²²⁵Ac and its daughter nuclides (²²¹Fr, ²¹³Bi) are well-separated (100, 218, 440 keV), non-equilibrium progeny in OARs can be identified by imaging with <100 keV resolution. However, the low administered activity in ²²⁵Ac TAT requires continuous measurement over several hours, necessitating a wearable dosimetry system. These miniaturized systems must balance energy resolution and linearity with constraints on form factor and power consumption, prohibiting the use of scintillators with linear energy response. This study aims to experimentally calibrate and evaluate a novel, scintillator-free, chip-scale ?-spectrometer [1] (<0.5 mm thin) by mapping incident ?-energy to the detector’s nonlinear energy response, enabling real-time monitoring of off-target toxicity.

Materials/Methods: To characterize the chip-scale ?-spectrometer’s nonlinear energy response across a range of relevant incident ?-energies, a custom test platform was developed and modeled using a simulation toolkit. Leveraging Compton scattering’s relationship between energy and scattering angle, the system, a motorized rotating stage supporting a source, collimator, and scattering layer, is capable of varying the unimodal peak ?-energy incident on the ?-spectrometer. The platform utilizes a 1 mCi ⁸⁹Zr source to emit 511 keV photons ensuring sufficient ?-flux for each scattering angle. Experimental validation will be performed using a commercial benchtop ?-spectrometer as a standard-of-comparison with the chip-scale spectrometer.

Results: Preliminary simulations confirm the setup’s ability to generate tunable ?-energies between 340–510 keV, including ²¹³Bi’s 440 keV emission. This corresponds to Compton scattering angles of 10-60°. Simulated energy modes closely match those predicted by Compton kinematics (R²=0.994), with particle counts decreasing beyond 35° as predicted by the Klein–Nishina formula. The spectra demonstrate fine energy resolution, achieving an average full-width at half maximum (FWHM) of ~15 keV. Experimental results will be presented in an updated abstract.

Conclusion: This method establishes an experimental mapping between various incident ?-energies and detector responses with the energy resolution necessary to identify off-target toxicity. By supporting the development of miniature, high-resolution ?-spectrometers, it lays the foundation for continuous monitoring of radiopharmaceutical uptake via a wearable dosimetry platform to inform patient-specific TAT dosing.