Quantitative SPECT/CT imaging forms the basis for internal dosimetry in molecular radiotherapies. While the conversion from counts to activity is typically based on conversion factors individually measured by each site, a recently introduced commercially available reconstruction (xSPECT Quant) offers a standardized and traceable calibration of SPECT/CT systems. The aim of this work was to assess the characteristics of xSPECT Quant in combination with ¹⁷⁷Lu as one of the most important radionuclides used in molecular radiotherapies and to compare it to a widely used ordered-subset expectation-maximization reconstruction (Flash3D). Methods: In a series of ¹⁷⁷Lu-filled phantom measurements, several important features were investigated for xSPECT Quant and Flash3D. Noise behavior and accuracy of the activity determination were evaluated in a large cylinder. Recovery coefficients were assessed in a hot-sphere phantom with and without background. Additionally, the resolutions were determined in a line source phantom as well as in a matched-filter resolution analysis of the hot-sphere-cold-background phantom. Results: Both reconstruction algorithms improve the spatial resolution at the cost of noise build-up. Despite its slower convergence, Flash3D features a more efficient recovery. Although resolution recovery methods are applied within both reconstructions, partial-volume errors-namely activity overestimation in the object center and spill-out of counts from the object edges-remain of relevance. In contrast to Flash3D, for which only the total number of updates (iterations × subsets) plays a role, the exact subdivision into iterations and subsets affected all characteristics of xSPECT Quant (optimum, 1 subset). The optimal trade-off between noise build-up and resolution improvement was found for 48 iterations and 1 subset, resulting in a quantitative accuracy of 1.2% in the Jaszczak cylinder (xSPECT Quant cross-calibrated to the dose calibrator). Conclusion: If the reconstruction parameters are chosen with care, both examined reconstructions can provide absolute quantitative SPECT images with high image quality (subcentimeter resolution at an acceptable noise build-up) as well as high quantitative accuracy (given a well-calibrated Flash3D conversion from counts to activity concentration). With its standardized (and traceable) activity determination, xSPECT Quant dispenses with site-specific calibration protocols, enabling a reliable activity determination comparable across sites, which is especially useful for multicentric molecular radiotherapy studies.

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