WE‐EF‐BRA‐04: Evaluation of Dosimetric Uncertainties in Individualized Targeted Radionuclide Therapy (TRT) Treatment Planning Using Pre‐Clinical Data

Abstract

Purpose:Dosimetry for targeted radionuclide therapy (TRT) is moving away from conventional model‐based methods towards patient‐specific approaches. To address this need, a Monte Carlo (MC) dosimetry platform was developed to estimate patient‐specific therapeutic 3D dose distributions based on pre‐treatment imaging. However, because a standard practice for patient‐specific internal dosimetry has not yet been established, there are many sources of dosimetric uncertainties. The goal of this work was to quantify the sensitivity of various parameters on MC dose estimations.Methods:The ‘diapeutic’ agent, CLR1404, was used as a proof‐of‐principle compound in this work. CLR1404 can be radiolabeled with either 12⁴I for PET imaging or 131I for radiotherapy or SPECT imaging. PET/CT images of 5 mice were acquired out to 240 hrs post‐injection of 12⁴I‐CLR1404. The therapeutic 131I‐CLR1404 absorbed dose (AD) distribution was calculated using a Geant4‐based MC dosimetry platform. A series of sensitivity studies were performed. The variables that were investigated included the PET/CT voxel resolution, partial volume corrections (PVC), material segmentation, inter‐observer contouring variability, and the pre‐treatment image acquisition frequency.Results:Resampling the PET/CT voxel size between 0.2–0.8 mm resulted in up to a 13% variation in the mean AD. Application of the PVC increased the mean AD by 0.5–11.2%. Less than 1% differences in ROI mean AD were observed between the tissue segmentation schemes using 4 and 27 different material compositions. Inter‐observer contouring variability led to up to a 20% CoV (stdev/mean) in the mean AD between the users. Varying the number and frequency of pre‐treatment images used resulted in changes in mean AD up to 176% compared to the case using all 12 images.Conclusion:Voxel resolution, contour segmentation, the image acquisition protocol most significantly impacted patient‐specific TRT dosimetry. Further work is needed to develop a standard protocol that optimizes accuracy and efficiency for patient‐specific internal dosimetry.BT and JG are affiliated with Cellectar Biosciences which owns the licensing rights to CLR1404 and related compounds.