question: RATIONALE: Salivary glands are highly perfused and express the prostate-specific membrane antigen (PSMA) receptor as well as the sodium—iodide symporter. As a consequence, treatment with (177)Lu/(225)Ac-PSMA for prostate cancer or (131)I for thyroid cancer leads to a high radiation dose in the salivary glands, and patients can be confronted with persistent xerostomia and reduced quality of life. Salivation can be inhibited using an antimuscarinic pharmaceutical, such as glycopyrronium bromide (GPB), which may also reduce perfusion. The primary objective of this work was to determine if inhibition with GPB could provide a considerable (> 30%) reduction in the accumulation of administered (123)I or (68)Ga-PSMA-11 in salivary glands. METHODS: Ten patients who already received a whole-body (68)Ga-PSMA-11 PET/CT scan for (re)staging of prostate cancer underwent a repeat PET/CT scan with tracer administration at 90 min after intravenous injection of 0.2 mg GPB. Four patients in follow-up after thyroid cancer, who had been treated with one round of ablative (131)I therapy with curative intent and had no signs of recurrence, received (123)I planar scintigraphy at 4 h after tracer administration without GPB and a repeated scan at least one week later, with tracer administration at 30 min after intramuscular injection of 0.4 mg GPB. Tracer uptake in the salivary glands was quantified on PET and scintigraphy, respectively, and values with and without GPB were compared. RESULTS: No significant difference in PSMA uptake in the salivary glands was seen without or with GPB (Mean SUL(mean) parotid glands control 5.57, intervention 5.72, p = 0.50. Mean SUL(mean) submandibular glands control 6.25, intervention 5.89, p = 0.12). Three out of 4 patients showed increased (123)I uptake in the salivary glands after GPB (Mean counts per pixel control 8.60, intervention 11.46). CONCLUSION: Muscarinic inhibition of salivation with GPB did not significantly reduce the uptake of PSMA-ligands or radioiodine in salivary glands, and can be dismissed as a potential strategy to reduce toxicity from radionuclide therapies.