What You See Is Not What You Get: On the Accuracy of Voxel-Based Dosimetry in Molecular Radiotherapy

Improvements in quantitative SPECT/CT have aroused growing interest in voxel-based dosimetry for radionuclide therapies, because it promises visualization of absorbed doses at a voxel level. In this work, SPECT/CT-based voxel-level dosimetry of a 3-dimensional (3D) printed 2-compartment kidney phantom was performed, and the resulting absorbed dose distributions were examined. Additionally, the potential of the PETPVC partial-volume correction tool was investigated. Methods: Both kidney compartments (70% cortex, 30% medulla) were filled with different activity concentrations, and SPECT/CT imaging was performed. The images were reconstructed using varying settings (iterations, subsets, and postfiltering). On the basis of these activity concentration maps, absorbed dose distributions were calculated with precalculated ¹⁷⁷Lu voxel S values and an empiric kidney half-life. An additional set of absorbed doses was calculated after applying PETPVC for partial-volume correction of the SPECT reconstructions. Results: SPECT/CT imaging blurs the 2 discrete suborgan absorbed dose values into a continuous distribution. Although this effect is slightly improved by applying more iterations, it is enhanced by additional postfiltering. By applying PETPVC, the absorbed dose values are separated into 2 peaks. Although this leads to a better agreement between SPECT/CT-based and nominal values, considerable discrepancies remain. In contrast to the calculated nominal absorbed doses of 7.8 and 1.6 Gy (in the cortex and medulla, respectively), SPECT/CT-based voxel-level dosimetry resulted in mean absorbed doses of 3.0-6.6 Gy (cortex) and 2.7-5.1 Gy (medulla). PETPVC led to improved ranges of 6.1-8.9 Gy (cortex) and 2.1-5.4 Gy (medulla). Conclusion: Our study showed that ¹⁷⁷Lu quantitative SPECT/CT imaging leads to voxel-based dose distributions largely differing from the real organ distribution. SPECT/CT imaging and reconstruction deficiencies might directly translate into unrealistic absorbed dose distributions, thus questioning the reliability of SPECT-based voxel-level dosimetry. Therefore, SPECT/CT reconstructions should be adapted to ensure an accurate quantification of the underlying activity and, therefore, absorbed dose in a volume of interest of the expected object size (e.g., organs, organ substructures, lesions, or voxels). As an example, PETPVC largely improves the match between SPECT/CT-based and nominal dose distributions. In conclusion, the concept of voxel-based dosimetry should be treated with caution. Specifically, one should remember that the absorbed dose distribution is mainly a convolved version of the underlying SPECT reconstruction.