Accuracy and uncertainty analysis of reduced time point imaging effect on time-integrated activity for 177Lu-DOTATATE PRRT in patients and clinically realistic simulations

Background Dosimetry promises many advantages for radiopharmaceutical therapies but repeat post-therapy imaging for dosimetry can burden both patients and clinics. Recent applications of reduced time point imaging for time-integrated activity (TIA) determination for internal dosimetry following 177 Lu-DOTATATE peptide receptor radionuclide therapy have shown promising results that allow for the simplification of patient-specific dosimetry. However, factors such as scheduling can lead to sub-optimal imaging time points, but the resulting impact on dosimetry accuracy is still under investigation. We use four-time point 177 Lu SPECT/CT data for a cohort of patients treated at our clinic to perform a comprehensive analysis of the error and variability in time-integrated activity when reduced time point methods with various combinations of sampling points are employed. Methods The study includes 28 patients with gastroenteropancreatic neuroendocrine tumors who underwent post-therapy SPECT/CT imaging at approximately 4, 24, 96, and 168 h post-therapy (p.t.) following the first cycle of 177 Lu-DOTATATE. The healthy liver, left/right kidney, spleen and up to 5 index tumors were delineated for each patient. Time-activity curves were fit with either monoexponential or biexponential functions for each structure, based on the Akaike information criterion. This fitting was performed using all 4 time points as a reference and various combinations of 2 and 3 time points to determine optimal imaging schedules and associated errors. 2 commonly used methods of single time point (STP) TIA estimation are also evaluated. A simulation study was also performed with data generated by sampling curve fit parameters from log-normal distributions derived from the clinical data and adding realistic measurement noise to sampled activities. For both clinical and simulation studies, error and variability in TIA estimates were estimated with various sampling schedules. Results The optimal post-therapy imaging time period for STP estimates of TIA was found to be 3–5 days (71–126 h) p.t. for tumor and organs, with one exception of 6–8 days (144–194 h) p.t. for spleen with one STP approach. At the optimal time point, STP estimates give mean percent errors (MPE) within ± 5% and SD