Abstract

A proof-of-concept is presented for an energy-dispersive X-ray fluorescence (EDXRF) system employing a 93 mCi 241Am source (59.5 keV) to excite gadolinium (Gd) biomarkers embedded in water-equivalent phantoms. Monte Carlo simulations, based on adapted PENELOPE routines (109 primary histories), were used to optimize both source and detector collimation and to predict absorbed-dose distributions. For a 1 cm-diameter target located at 5 cm depth, simulations showed that a conical collimation geometry applied to both source and detector yields a signal-to-noise ratio (SNR) of 6000 ± 381 % at 0.5 mmol mL?1 Gd and 400 ± 95 % at 0.063 mmol mL?1. These represent 2-fold and 3.4-fold improvements, respectively, compared to single-collimator and fully divergent setups. Experimental validation confirmed these trends and established detection limits below 0.031 mmol mL?1 (approximately 0.5 % w/w, equivalent to one-sixteenth the commercial OMNISCAN concentration). Tumor-sized volumes (?1 cm) infused with ?1 % w/w Gd were reliably detected at 5 cm depth, while keeping the phantom-averaged absorbed dose below 1 mGy during a 15-min acquisition. These findings demonstrate that a compact, radioisotope-based confocal EDXRF system can achieve clinically meaningful Gd sensitivity with sub-centimeter spatial resolution, establishing a foundation for accelerated imaging using large-area detector arrays. © 2025 Elsevier Ltd