Tumor Sink Effect in 18F-PSMA PET/CT

Objective:To examine the impact of the tumor burden on the biodistribution of 18F-PSMA in PET imaging by quantitative measurements. Methods:This retrospective analysis included 100 males with prostate cancer who underwent 18F-PSMA PET/CT. For each prostate cancer lesion, the metabolic tumor volume (PSMA-TV) was measured via an automatic segmentation tool based on 50% threshold using syngovia software. Then, the “total lesion PSMA expression” (TL-PSMA) was calculated by multiplying PSMA-TV by SUVmean of each lesion. The whole-body PSMA tumor burden is the sum of TL-PSMA values of all lesions in each patient. Based on this tumor burden, patients were divided by quintiles into 5 groups. A very low (tumor burden ≤ 400), low (401-1250), moderate (1251 – 2500), high (2501 - 6500), and very high (≥ 6501) whole body total lesion PSMA-expression (TL-PSMA) or tumor burden. Correlation between tumor burden and SUVmax/SUVmean of reference background organs was conducted. Reference organs which were used as representative for the normal background tissue uptake were the parotid glands, lacrimal glands, liver, spleen and kidneys. Results:Tumor burden showed a moderate negative correlation with the SUVmean of the right kidney (p < 0.001), left kidney (p< 0.001), right parotid gland (p< 0.001), left parotid gland (p< 0.001), and left lacrimal gland (p= 0.001) and a weak negative correlation with the SUVmean of right lacrimal gland (p= 0.001), liver (p= 0.013) and spleen (p= 0.045). Patients with a very high tumor burden (group 5, ≥ 6500) had a significantly lower PSMA uptake in reference organs compared to other groups (p< 0.001).Conclusion:Tumor sequestration affects 18F-PSMA 1007 biodistribution in normal organs. As tumor sink effect may occur with PSMA-targeted radioligand therapy (RLT), patients with very high tumor burden might benefit from higher therapeutic doses without exceeding the radiation dose limit for organs at risk.