PSMA PET/CT Identifies Intrapatient Variation in Salivary Gland Toxicity From Iodine-131 Therapy

INTRODUCTION: Xerostomia is a well-known complication after iodine-131 ((131)I) therapy for thyroid carcinoma. It is currently insufficiently understood how the dose and biodistribution of (131)I relates to salivary gland toxicity, and whether this is consistent for all salivary glands within a single patient. Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) was recently introduced as a new tool to evaluate the relative loss of vital acinar cells in individual salivary glands. We aimed to assess gland-specific salivary gland toxicity after (131)I-therapy using PSMA PET/CT. METHODS: Five patients with differentiated thyroid cancer underwent [(68)Ga]Ga-PSMA-11 PET/CT to evaluate their eligibility for peptide radioligand therapy with [(177)Lu]Lu-PSMA-617. Uptake patterns in salivary glands were evaluated visually and quantitatively as an indicator of vital acinar cell loss after prior (131)I-therapy. RESULTS: Four of 5 patients demonstrated significant lowered uptake in at least one salivary gland, after receiving at least 2 (131)I-treatments. Asymmetric loss of vital acinar cells occurred by gland type (parotid/submandibular) and location (right/left). The other salivary glands in these patients and all salivary glands in the fifth patient showed normal uptake, demonstrating high intrapatient and interpatient variability. CONCLUSIONS: (131)I-therapy can induce salivary gland toxicity with high inter- but also high intrapatient variation among separate gland locations, which can be assessed with PSMA PET/CT. This new technique offers potential to guide further development and evaluation of protective measures in patients receiving (131)I-therapy.