Kinetic modeling of (68)Ga-PSMA-11 and validation of simplified methods for quantification in primary prostate cancer patients

BACKGROUND: The positron emission tomography (PET) ligand (68)Ga-Glu-urea-Lys(Ahx)-HBED-CC ((68)Ga-PSMA-11) targets the prostate-specific membrane antigen (PSMA), upregulated in prostate cancer cells. Although (68)Ga-PSMA-11 PET is widely used in research and clinical practice, full kinetic modeling has not yet been reported nor have simplified methods for quantification been validated. The aims of our study were to quantify (68)Ga-PSMA-11 uptake in primary prostate cancer patients using compartmental modeling with arterial blood sampling and to validate the use of standardized uptake values (SUV) and image-derived blood for quantification. RESULTS: Fifteen patients with histologically proven primary prostate cancer underwent a 60-min dynamic (68)Ga-PSMA-11 PET scan of the pelvis with axial T1 Dixon, T2, and diffusion-weighted magnetic resonance (MR) images acquired simultaneously. Time-activity curves were derived from volumes of interest in lesions, normal prostate, and muscle, and mean SUV calculated. In total, 18 positive lesions were identified on both PET and MR. Arterial blood activity was measured by automatic arterial blood sampling and manual blood samples were collected for plasma-to-blood ratio correction and for metabolite analysis. The analysis showed that (68)Ga-PSMA-11 was stable in vivo. Based on the Akaike information criterion, (68)Ga-PSMA-11 kinetics were best described by an irreversible two-tissue compartment model. The rate constants K(1) and k(3) and the net influx rate constants K(i) were all significantly higher in lesions compared to normal tissue (p < 0.05). K(i) derived using image-derived blood from an MR-guided method showed excellent agreement with K(i) derived using arterial blood sampling (intraclass correlation coefficient = 0.99). SUV correlated significantly with K(i) with the strongest correlation of scan time-window 30–45 min (rho 0.95, p < 0.001). Both K(i) and SUV correlated significantly with serum prostate specific antigen (PSA) level and PSA density. CONCLUSIONS: (68)Ga-PSMA-11 kinetics can be described by an irreversible two-tissue compartment model. An MR-guided method for image-derived blood provides a non-invasive alternative to blood sampling for kinetic modeling studies. SUV showed strong correlation with K(i) and can be used in routine clinical settings to quantify (68)Ga-PSMA-11 uptake.