Dose Heterogeneity in Transarterial Radioembolization after Fractional Administration of Holmium Microspheres: A Study in Perfused Human Tumor-Bearing Liver Explants under MR Imaging

Purpose: To investigate dose heterogeneity in liver tumors and nontumor target liver (NTTL) following transarterial radioembolization (TARE) by developing an experimental magnetic resonance (MR) imaging–compatible ex vivo perfusion model based on human tumor-bearing livers and to validate the observed heterogeneity patterns against in vivo data.

Materials and Methods: Fractionated TARE was performed under MR imaging in 4 machine-perfused human tumor-bearing liver explants using fluorescent holmium microspheres. Dose heterogeneity was quantified by calculating the homogeneity index (HI) from MR imaging–based dose maps (voxel size, <2.5 mm). These results were validated against HI values from 2 TARE-treated patients. Fluorescence microscopy was used to assess the microscopic distribution of 4 distinct microsphere fractions.

Results: MR imaging–based dose maps revealed lower heterogeneity in liver tumors (mean HI, 2.41; range, 0.72–4.43) than in nontumor target liver (mean HI, 2.95; range, 1.58–5.94); however, this difference was not significant (P = .06) and was primarily driven by higher microsphere concentrations in tumors, which were associated with reduced heterogeneity (ρ = −0.88, P < .001). Microspheres administered in consecutive fractions decreased the HI while mostly preserving the spatial distribution pattern of earlier fractions, as confirmed by fluorescence microscopy.

Conclusions: TARE induces heterogeneous dose distributions in both liver tumors and nontumor target liver at a scale below the resolution of nuclear imaging. Although these findings provide insight into microsphere distribution and dose heterogeneity, the clinical significance of fine-scale dose heterogeneity and its potential impact on treatment outcomes remains uncertain and warrants further investigation.