Quantitative Imaging Evaluation of Structural and Densitometric Changes in Major Salivary Glands After 177Lu PSMA...

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.

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.

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.

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.