Tumor Sink Effect with Prostate-Specific Membrane Antigen-Targeted Theranostics in Patients with Metastatic Castration-Resistant Prostate Cancer: Intra-Individual Evaluations
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Updated: Jul 30, 2025
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Caroline Burgard1, Florian Rosar1, Robert J Marlowe2
1Department of Nuclear Medicine, Saarland University-Medical Center, 66421 Homburg, Germany.
Abstract:
"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.
Insights
Tumor sink effects, where tumors sequester radiopharmaceuticals, were studied in patients with metastatic castration-resistant prostate cancer. Findings suggest these effects impact salivary glands and spleen uptake of PSMA-targeted agents.
Area of Science:
- Nuclear Medicine
- Radiopharmaceutical Therapy
- Oncology
Background:
- Tumor sink effects, characterized by decreased radiopharmaceutical uptake in healthy tissues due to tumor sequestration, can influence radioligand therapy (RLT) outcomes.
- Understanding these effects is crucial for optimizing RLT toxicity and dosing strategies, particularly for prostate-specific membrane antigen (PSMA)-targeted agents.
Purpose of the Study:
- To investigate tumor sink effects of PSMA-targeted radiopharmaceuticals in organs-at-risk in patients with metastatic castration-resistant prostate cancer (mCRPC).
- To analyze the impact of RLT on radiopharmaceutical distribution and uptake in healthy tissues.
Main Methods:
- Retrospective analysis of 33 mCRPC patients treated with 177Lu-PSMA-617.
- Three intra-individual comparisons were performed using 68Ga-PSMA-11 PET/CT scans before and after RLT.
- Correlations between total lesional PSMA uptake (TLP) and organ mean standardized uptake values (SUVmean) were assessed.
Main Results:
- A significant inverse correlation was observed between changes in TLP and SUVmean in the parotid glands and spleen post-RLT.
- In RLT responders, organ SUVmean in the salivary glands and spleen significantly increased after treatment.
- Baseline TLP and SUVmean showed significant negative correlations in these organs, supporting the presence of tumor sink effects.
Conclusions:
- Tumor sink effects are suggested in the salivary glands and spleen of mCRPC patients receiving PSMA-targeted radiopharmaceuticals.
- These findings highlight the importance of considering tumor sequestration when evaluating radiopharmaceutical distribution and potential toxicity in RLT.
