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

We aimed to systematically determine the impact of tumor burden on Ga-68-prostate-specific membrane antigen-11 (Ga-68-PSMA) PET biodistribution by the use of quantitative measurements. Methods: This international multicenter, retrospective analysis included 406 men with prostate cancer who underwent Ga-68-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 Ga-68-PSMA PET images, and SUVmean was obtained. Correlations between the SUVmean 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 SUVmean 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 SUVmean of the salivary glands (r = -0.44, P<0.001), kidneys (r = -0.34, P<0.001), and liver (r = -0.30, P < 0.001) and a weak negative correlation with the spleen SUVmean (r = -0.16, P = 0.002). Patients with a very high PSMA-VOL (quintile 5, >= 1,355 cm(3)) had a significantly lower PSMA uptake in the salivary glands, kidneys, liver, and spleen than did the control group, with an average difference of -38.1%, -40.0%, -43.2%, and -34.9%, respectively (P<0.001). Conclusion: Tumor sequestration affects Ga-68-PSMA biodistribution in normal organs. Patients with a very high tumor load showed a significantly lower uptake of Ga-68-PSMA in normal organs, confirming a tumor sink effect. As similar effects might occur with PSMA-targeted radioligand therapy, these patients might benefit from increased therapeutic activity without exceeding the radiation dose limit for organs at risk.

Automated summary

We systematically determined the impact of tumor burden on Ga-68-PSMA PET biodistribution using quantitative measurements. The study found that patients with a very high tumor load showed significantly lower uptake of Ga-68-PSMA in normal organs, which could have implications for PSMA-targeted radioligand therapy.