Abstract

Purpose: Partial volume effects have been shown to introduce a significant error in positron emission tomography (PET) quantitation. In this study, we investigated the impact of PET partial volume correction (PVC) on the dosimetry of PET‐based targeted radionuclide therapy (TRT) planning. Methods: Five tumor‐bearing nude mice were injected with ∼230 μCi of a 124I‐CLR1404, a small‐molecule, phospholipid ether analog featuring selective retention and accumulation in malignant cells. PET/CT data were acquired at 1, 6, 12, 24, 36, 48, 60, 72, 96, 120, 168, and 240 hours post injection and reconstructed with and without PVC using an OSEM3D algorithm. Assuming identical uptake between 124I‐CLR1404 and its therapeutic analog, 131I‐CLR1404, absorbed doses of 131I‐CLR1404 were modeled by applying a piecewise trapezoidal integration to the 124I‐CLR1404 kinetics. Dose volume histograms (DVHs) and normalized differential DVHs (dDVHs) were used to quantify the impact of PVC on PET‐based TRT planning. Results: Partial volume corrected PET images showed higher tumor uptake, increased the recovery of tumor heterogeneity structures, and a generally improved recovery of small normal tissue structures such as the heart ventricles. In tumors, the mean and maximum 124I‐CLR1404 standardized uptake value at peak drug concentration increased by 1.95±0.86% and 34.97±9.36%, respectively. DVHs of planned 131I‐CLR1404 doses showed an increase in maximum tumor dose levels by 15.63±3.53% due to PVC. Tumor dDVHs confirmed a shift towards higher therapeutic doses with an average increase of 13.09±1.21 mGy per mCi of injected 131I‐CLR1404 activity. Conclusion: PVC of PET data more accurately recovered the biodistribution of 124I‐CLR1404 and thus further improved TRT planning and delivery by increasing the quantitative accuracy. PVC will especially benefit the identification of cold spots in the target volume and the dose estimation in dose limiting organs. JJG and JPWare affiliated with Novelos Therapeutics, Inc., which owns the licensing rights to CLR1404 and related compounds.

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