The aim of this work was to find an optimal setup for activity determination of Lu-177-based SPECT/CT imaging reconstructed with 2 commercially available methods (xSPECT Quant and Flash3D). For this purpose, 3-dimensional (3D)-printed phantoms of different geometries were manufactured, different partial-volume correction (PVC) methods were applied, and the accuracy of the activity determination was evaluated. Methods: A 2-compartment kidney phantom (70% cortical and 30% medullary compartment), a sphere, and an ellipsoid of equal volumes were 3D printed, filled with Lu-177, and scanned with a SPECT/CT system. Reconstructions were performed with xSPECT and Flash3D. Different PVC methods were applied to find an optimal quantification setup: method 1 was a geometry-specific recovery coefficient based on the 3D printing model, method 2 was a geometry-specific recovery coefficient based on the low-dose CT scan, method 3 was an enlarged volume of interest including spilled-out counts, method 4 was activity concentration in the peak milliliter applied to the entire CT-based volume, and method 5 was a fixed threshold of 42% of the maximum in a large volume containing the object of interest. Additionally, the influence of postreconstruction gaussian filtering was investigated. Results: Although the recovery coefficients of sphere and ellipsoid differed by only 0.7%, a difference of 31.7% was observed between the sphere and the renal cortex phantoms. Without post-filtering, the model-based recovery coefficients (methods 1 and 2) resulted in the best accuracies (xSPECT, 1.5%; Flash3D, 10.3%), followed by the enlarged volume (method 3) (xSPECT, 8.5%; Flash3D, 13.0%). The peak-milliliter method (method 4) showed large errors only for sphere and ellipsoid (xSPECT, 23.4%; Flash3D, 21.6%). Applying a 42% threshold (method 5) led to the largest quantification errors (xSPECT, 32.3%; Flash3D, 46.7%). After postfiltering, a general increase in the errors was observed. Conclusion: In this work, 3D printing was used as a prototyping technique for a geometry-specific investigation of SPECT/CT reconstruction parameters and PVC methods. The optimal setup for activity determination was found to be an unsmoothed SPECT/CT reconstruction in combination with a recovery coefficient based on the low-dose CT. The difference between spheric and renal recovery coefficients suggests that the typically applied volume-dependent but only sphere-based recovery coefficient lookup tables should be replaced by a more geometry-specific alternative.