“Tumor sink effects”, decreased physiological uptake of radiopharmaceuticals due to sequestration
by a tumor, may impact radioligand therapy (RLT) toxicity and dosing. We investigated these effects with
prostate-specific membrane antigen (PSMA)-targeted radiopharmaceuticals in the healthy organs-at-risk (the
parotid glands, kidneys, liver, and spleen) of 33 patients with metastatic castration-resistant prostate cancer
(mCRPC). We retrospectively performed three intra-individual comparisons. First, we correlated changes
from baseline to post-RLT (after two 177-lutetium (177Lu)-PSMA-617 cycles) in total lesional PSMA (∆TLP)
and organ mean standardized uptake values (∆SUVmean). Second, in 25 RLT responders, we compared
the organ SUVmean post-RLT versus that at baseline. Lastly, we correlated the baseline TLP and organ
SUVmean. Data were acquired via 68-gallium-PSMA-11 positron emission tomography before the first and
after the second 177Lu-PSMA-617 cycle. In the parotid glands and spleen, ∆TLP and ∆SUVmean showed
a significant inverse correlation (r = −0.40, p = 0.023 and r = −0.36, p = 0.042, respectively). Additionally,
in those tissues, the median organ SUVmean rose significantly from baseline after the response to RLT
(p ≤ 0.022), and the baseline TLP and SUVmean were significantly negatively correlated (r = −0.44, p = 0.01
and r = −0.42, p = 0.016, respectively). These observations suggest tumor sink effects with PSMA-targeted
radiopharmaceuticals in the salivary glands and spleen of patients with mCRPC