Muscarinic inhibition of salivary glands with glycopyrronium bromide does not reduce the uptake of PSMA-ligands or radioiodine

Abstract

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 177Lu/225Ac-PSMA for prostate cancer or 131I 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 123I or 68Ga-PSMA-11 in salivary glands. Methods Ten patients who already received a whole-body 68Ga-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 131I therapy with curative intent and had no signs of recurrence, received 123I 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 SULmean parotid glands control 5.57, intervention 5.72, p = 0.50. Mean SULmean submandibular glands control 6.25, intervention 5.89, p = 0.12). Three out of 4 patients showed increased 123I 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.

Safety of High-Dose Botulinum Toxin Injections for Parotid and Submandibular Gland Radioprotection

“…All previous attempts with various drugs including monotherapy with anticholinergics failed to overcome this therapy-limiting side-effect [3,4]. Patients with differentiated thyroid cancer treated with radioactive iodine ( 131 I) are also at risk of permanent xerostomia.…”

Global experience with PSMA-based alpha therapy in prostate cancer

“…if successful, may have a great impact on the practice of PRLT of mCRPC [ 104 ]. Other pharmacologic interventions that have been tried for their ability to reduce salivary gland uptake of PSMA radioligands are botulinum injection, anti-cholinergic use, and injection of local anesthetic agents [ 105 , 106 ]. Sialendoscopy with dilatation, saline irrigation, and steroid injection into the ducts of major salivary glands has been attempted to ameliorate the impact of xerostomia in patients treated with 225 Ac-PSMA TAT [ 107 ].…”

Sublingual Atropine Administration as a Tool to Decrease Salivary Glands’ PSMA-Ligand Uptake: A Preclinical Proof of Concept Study Using [68Ga]Ga-PSMA-11

“…Atropine is an old and well-known molecule, and is routinely used via intravenous administration as a preoperative medication for the reduction of salivary and bronchial secretions or as eye drops for inducing mydriasis for diagnostic purposes. Despite the absence of an adapted galenic form and robust safety data using this route, sublingual administration is regularly used off-label, is documented for the treatment of drooling even in children, and is still studied in clinical trials [24][25][26][27][28][29]. As used for the management of sialorrhea, one or two drops (0.5 to 1 mg) of 1% atropine eye drops every 4 to 6 h (<10 mg/day) are described as being tolerable with low frequency, and with reversible side effects [27,30].…”