Tumor Sink Effect in 68Ga-PSMA-11 PET: Myth or Reality?

We aimed to systematically determine the impact of tumor burden on (68)Ga-prostate-specific membrane antigen-11 ((68)Ga-PSMA) PET biodistribution by the use of quantitative measurements. Methods: This international multicenter, retrospective analysis included 406 men with prostate cancer who underwent (68)Ga-PSMA PET/CT. Of these, 356 had positive findings and were stratified by quintiles into a very low (quintile 1, ≤25 cm(3)), low (quintile 2, 25–189 cm(3)), moderate (quintile 3, 189–532 cm(3)), high (quintile 4, 532–1,355 cm(3)), or very high (quintile 5, ≥1,355 cm(3)) total PSMA-positive tumor volume (PSMA-VOL). PSMA-VOL was obtained by semiautomatic segmentation of total tumor lesions using qPSMA software. Fifty prostate cancer patients with no PSMA-positive lesions (negative scan) served as a control group. Normal organs, which included salivary glands, liver, spleen, and kidneys, were semiautomatically segmented using (68)Ga-PSMA PET images, and SUV(mean) was obtained. Correlations between the SUV(mean) of normal organs and PSMA-VOL as continuous and categoric variables by quintiles were evaluated. Results: The median PSMA-VOL was 302 cm(3) (interquartile range [IQR], 47–1,076 cm(3)). The median SUV(mean) of salivary glands, kidneys, liver, and spleen was 10.0 (IQR, 7.7–11.8), 26.0 (IQR, 20.0–33.4), 3.7 (IQR, 3.0–4.7), and 5.3 (IQR, 4.0–7.2), respectively. PSMA-VOL showed a moderate negative correlation with the SUV(mean) of the salivary glands (r = −0.44, P