Day-to-day variability of [(68)Ga]Ga-PSMA-11 accumulation in primary prostate cancer: effects on tracer uptake and visual interpretation

PURPOSE: Prostate-specific membrane antigen (PSMA) agents, such as [(68)Ga]Ga-PSMA-11, have an unprecedented accuracy in staging prostate cancer (PCa) and detecting disease recurrence. PSMA PET/CT may also be used for response monitoring by displaying molecular changes, instead of morphological changes alone. However, there are still limited data available on the variability in biodistribution and intra-prostatic uptake of PSMA targeting radiotracers. Therefore, the aim of this study was to assess the repeatability of [(68)Ga]Ga-PSMA-11 uptake in primary PCa patients in a 4-week interval. METHODS: Twenty-four primary PCa patients were prospectively included, who already were scheduled for [(68)Ga]Ga-PSMA-11 PET/CT scan on clinical indication (≥ cT3, Gleason score ≥ 7 or PSA ≥ 20 ng/mL). These patients received two [(68)Ga]Ga-PSMA-11 PET/CT scans with a 4-week interval. No treatment was started in between the scans. Semiquantitative measurements (SUL(max), SUL(mean), and SUL(peak)) were determined in the prostate tumor, normal tissues, and blood pool. The repeatability coefficient of every region was determined. All scans were visually analyzed by two nuclear medicine physicians. RESULTS: Within-subject coefficient of variation of [(68)Ga]Ga-PSMA-11 uptake between the two scans was on average 10% in the prostate tumor, normal tissues (liver, kidney, parotid), and blood pool. The repeatability coefficient of the prostate tumor was 18% for SUL(peak) and 22% for SUL(max). Lesion uptake was visually different in 5 patients, though not clinically relevant. CONCLUSION: Results of test-retest [(68)Ga]Ga-PSMA-11 PET/CT scans in a 4-week interval show that [(68)Ga]Ga-PSMA-11 uptake is repeatable, with a clinical irrelevant variation in tumor and physiological distribution. Based on the presented repeatable uptake, [(68)Ga]Ga-PSMA-11 PET/CT scans can potentially be used for disease surveillance and therapy response monitoring. Changes in uptake larger than the RC are therefore likely to reflect actual biological changes in PSMA expression. Trial registration NL8263 at Trialregister.nl retrospectively registered on 03-01-2020. https://www.trialregister.nl/trial/8263