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.