Abstract
RationaleSalivary 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.MethodsTen 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.ResultsNo 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).ConclusionMuscarinic 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.
Highlights
Salivary gland toxicity after radionuclide therapy Salivary gland toxicity, especially xerostomia, is a serious side effect of several radionuclide therapies (RNTs)
Effect of glycopyrronium bromide (GPB) on prostate-specific membrane antigen (PSMA)‐ligand uptake Demographics The 10 male patients had an average age of 72 years
This work demonstrated that premedication with GPB did not significantly reduce the uptake of PSMA-ligands or radioiodine in the salivary glands, despite successful functional inhibition of the glands resulting in patients complaining of a dry mouth
Summary
Salivary gland toxicity after radionuclide therapy Salivary gland toxicity, especially xerostomia, is a serious side effect of several radionuclide therapies (RNTs). Mohan et al EJNMMI Res (2021) 11:25 prostate-specific membrane antigen (PSMA)-targeted radioligand therapy, for patients with metastatic prostate cancer using [177Lu]Lu- or [225Ac]Ac-PSMA ligands [5,6,7,8,9,10]. Both these systemic RNTs target only tissues that express specific proteins; the sodium iodide symporter (NIS) in the case of 131I therapy and the PSMA receptor in the case of PSMA therapy. A large fraction of the uptake of PSMA-ligands in the salivary glands is hypothesised to be non-specific in nature and does not involve the receptor [18, 19]
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