Background: Personalized dosimetry for Lu-177-PSMA treatment requires multiple-time-point SPECT/CT scans to calculate time-integrated activity (TIA). This study evaluates two-time-point (TTP) methods for TIA calculation for kidneys and tumors. Methods: A total of 18 patients treated with 3.7-7.4 GBq Lu-177 PSMA-617 were analyzed retrospectively, including 18 sets of left and right kidneys, as well as 45 tumors. Four quantitative SPECT/CT (4TP) were acquired at 2 h, 20 h, 40 h, 60 h (n = 11), or 200 h (n = 7) after treatment, and they were fit bi-exponentially as reference. The TTP method was fitted by a mono-exponential washout function using two selected imaging time points for kidneys. For tumors, one uptake and one washout phase were modeled, assuming linear (type I) and same (type II) uptake phase between 0 h to the first time point and mono-exponential washout thereafter. Two single-time-point (STP) methods were also implemented for comparison. TIA calculated by TTP and STP methods were compared with reference to the 4TP TIA. Results: For the kidneys, the TTP methods using 20 h-60 h and 40 h-200 h had smaller mean absolute errors of 8.05 ± 6.05% and 4.95 ± 3.98%, respectively, as compared to other combinations of time points and STP methods. For tumors, the type I and type II TTP methods using 20h−60 h and 40–200 h had smaller mean absolute errors of 6.14 ± 5.19% and 12.22 ± 4.44%, and 8.31 ± 7.16% and 4.48 ± 7.10%, respectively, as compared to other TTP and STP methods. Conclusion: The TTP methods based on later imaging time demonstrated fewer errors than the STP methods in kidney and tumor TIA. Imaging at 20 h−60 h and 40 h−200 h could simplify the dosimetry procedures with fewer TIA estimation errors.