Tumor Sink Effect in 68Ga-Psma-11 PET: Myth or Reality?
JOURNAL OF NUCLEAR MEDICINE(2022)
Abstract
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.
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Key words
PET,tumor sink effect,prostate cancer,PSMA,Ga-PSMA,radioligand therapy
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