Abstract
Purpose: he efficacy of targeted radionuclide therapy (TRT) depends on the ability to accurately characterize the absorbed dose distribution within tumors as well as other potential dose limiting organs. Clinical data suggests a compelling need for personalized dosimetry given that conventional dose calculation methods fail to accurately predict dose response relationships. This work describes the implementation of a Monte Carlo patient‐specific 3D dosimetry platform for TRT. Methods: CLR1404, a small‐molecule, phospholipid ether analog can serve as a ‘diapeutic’ (diagnostic and therapeutic) agent for the detection and treatment of multiple solid tumors. Because both the I–124 labeled imaging and I–131 labeled therapy agent are administered in similar mass doses, they are expected to display equivalent in vivo pharmacokinetic profiles. Therefore, the 124I‐CLR1404 distribution can be converted to the therapeutic 131I‐CLR1404 distribution by simply accounting for the difference in decay rates. In this study, high grade Glioma patients were scanned at 4.5, 24, and 48 hours post injection of 124I‐CLR1404. PET, CT and MRI images were co‐registered, resampled to the CT resolution and contoured. The 131I‐CLR1404 dose deposition throughout the CT volume was simulated using the Monte Carlo code Geant4.9.4 assuming a source strength in each voxel was proportional to the PET activity. The total cumulated absorbed dose was calculated by numerically integrating the activity over all time on a voxel‐by‐voxel basis. Results: Spatial distributions of the absorbed dose rates, DVHs, and mean, minimum, maximum, and total dose rate values for each contoured region were generated for each time point, clearly illustrating CLR1404's pharmacokinetic properties. The mean cumulated absorbed dose within tumor was 52.3 mGy per injected activity of 131I‐CLR1404. Conclusion: This work demonstrates that a Geant4 based Monte Carlo radiopharmaceutical dose calculation platform is not only feasible, but can serve as invaluable tool for personalized dosimetry in TRT. JJG and JPW are affiliated with Novelos Therapeutics which owns the licensing rights to CLR1404 and related compounds.
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