Evaluating Gold Nanoparticles for Preoperative SABR Treatment Planning of Intact Breast Cancer: From Imaging and Planning to Radiosensitization
Abstract
Purpose
To evaluate the feasibility of using a 4.2 MV imaging beam for simultaneous guidance and biologically enhanced delivery of preoperative stereotactic ablative radiotherapy (SABR) to intact breast tumors loaded with gold nanoparticles (AuNPs), and evaluate the expected radiosensitization effect.
Methods
We assessed physical contrast and biological radiosensitization for a 4.2 MV-CBCT beam (Siemens ONCOR) against a standard 6 MV flattening-filter-free (FFF) beam. First, we imaged 15 nm AuNPs at different concentrations up to 20 mg Au/mL in a breast phantom using diagnostic CT and 4.2 MV-CBCT to determine detectability. Second, we performed EGSnrc-based Monte Carlo treatment planning for two intact breast cases (20–24 Gy single-fraction), comparing AuNP-enhanced coplanar IMRT plans, modeling both intratumoral and intravenous distributions of AuNPs, against clinical non-coplanar 4π SABR benchmarks. We quantified target coverage, homogeneity index (HI), and organ-at-risk (OAR) sparing. Finally, we measured in vitro radiosensitization by quantifying γH2AX DNA damage foci in MDA-MB-231 cells irradiated (0–3 Gy) with and without AuNPs.
Results
AuNPs produced segmentable contrast in both diagnostic CT (~600 HU above tissue background) and MV-CBCT (~50 HU), facilitating target definition even with the spectral hardening. In planning studies, AuNP-enhanced coplanar IMRT improved dose homogeneity (HI improved from 0.34 to 0.21) and decreased dose spill-off (GTVrim spill-off reduced from 35% to 3%) relative to 4π SABR benchmarks, while maintaining heart and lung doses below toxicity threshold (mean dose <1 Gy). Moreover, the 4.2 MV beam yielded a higher biological effect, with a radiosensitization factor of 1.51 ± 0.09 compared to the 6 MV-FFF beam 1.33 ± 0.07 (p<0.001), confirming the spectral advantage of the lower energy beam driven by photoelectric absorption.
Conclusion
Repurposing a low-energy 4.2 MV IGRT beam for AuNP-loaded breast tumors achieves superior radiosensitization and sufficient imaging contrast, enabling simplified coplanar SABR workflows without compromising plan quality.