Ann Nucl Med. 2026 Jul 26. doi: 10.1007/s12149-026-02266-1. Online ahead of print.
ABSTRACT
OBJECTIVE: Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) provides a survival advantage in metastatic castration-resistant prostate cancer (mCRPC). However, the physiologically high PSMA-ligand uptake in salivary glands makes these organs susceptible to radiation damage. The aim of this study is to examine the changes occurring in salivary glands after PSMA-RLT and to evaluate their relationship with treatment-related parameters, including cumulative administered activity and number of RLT cycles.
METHOD: The study included 68 mCRPC patients who received 177Lu PSMA-617 treatment. Volume, surface area, density, and PSMA uptake levels were calculated for the parotid and submandibular glands in pre- and post-treatment imaging. Treatment-related changes and their associations with baseline imaging parameters, treatment timing, cumulative administered activity, and number of RLT cycles were statistically analyzed.
FINDINGS: After RLT, parotid glands showed significant decreases in SUVmean, volume, surface area, and PSMA total activity (all p < 0.001), whereas parotid density remained stable. Submandibular glands also demonstrated significant reductions in SUVmean, volume, surface area, PSMA total activity, and CT-derived density (all p < 0.001). In the exploratory correlation analyses, the number of RLT cycles and cumulative administered activity showed weak nominal positive associations with parotid density change; however, these associations did not remain statistically significant after Benjamini-Hochberg false discovery rate correction. BMI was not significantly associated with glandular SUVmean, HU measurements, or post-treatment glandular changes after correction for multiple testing.
CONCLUSION: PSMA-targeted RLT was associated with significant imaging-detectable structural alterations and reductions in PET-derived glandular activity in the major salivary glands. CT-derived density significantly decreased in the submandibular glands, whereas parotid density remained stable. No baseline imaging-, BMI-, time-, or administered activity-related parameter remained significantly associated with post-treatment glandular changes after correction for multiple testing.
PMID:42503048 | DOI:10.1007/s12149-026-02266-1
