Tumor Sink Effect with Prostate-Specific Membrane Antigen-Targeted Theranostics in Patients with Metastatic...

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.