Mohan V, Bruin N M, Tesselaar M E T, de Boer J P, Vegt E, Hendrikx J J M A, Al-Mamgani A, van de Kamer J B, Sonke J-J, Vogel W V
Department of Radiation Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066 CX, The Netherlands.
Department of Nuclear Medicine, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
EJNMMI Res. 2021 Mar 12;11(1):25. doi: 10.1186/s13550-021-00770-1.
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 Lu/Ac-PSMA for prostate cancer or 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 I or Ga-PSMA-11 in salivary glands.
Ten patients who already received a whole-body 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 I therapy with curative intent and had no signs of recurrence, received 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.
No significant difference in PSMA uptake in the salivary glands was seen without or with GPB (Mean SUL parotid glands control 5.57, intervention 5.72, p = 0.50. Mean SUL submandibular glands control 6.25, intervention 5.89, p = 0.12). Three out of 4 patients showed increased I uptake in the salivary glands after GPB (Mean counts per pixel control 8.60, intervention 11.46).
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.
唾液腺血供丰富，表达前列腺特异性膜抗原（PSMA）受体以及钠碘同向转运体。因此，用镥/锕-PSMA治疗前列腺癌或用碘治疗甲状腺癌会导致唾液腺接受高辐射剂量，患者可能会面临持续性口干和生活质量下降的问题。可以使用抗毒蕈碱药物（如格隆溴铵，GPB）抑制唾液分泌，这也可能会减少血供。这项研究的主要目的是确定GPB抑制是否能使唾液腺中注入的碘或镓-PSMA-11的蓄积量显著降低（>30%）。
10例已接受全身镓-PSMA-11 PET/CT扫描用于前列腺癌（再）分期的患者，在静脉注射0.2mg GPB 90分钟后注射示踪剂，进行重复PET/CT扫描。4例甲状腺癌随访患者，已接受一轮旨在治愈的消融性碘治疗且无复发迹象，在未使用GPB的情况下，于注射示踪剂4小时后进行碘平面闪烁显像，并至少在一周后进行重复扫描，在肌肉注射0.4mg GPB 30分钟后注射示踪剂。分别在PET和闪烁显像上对唾液腺中的示踪剂摄取进行定量，并比较使用和未使用GPB时的值。
无论是否使用GPB，唾液腺中PSMA摄取均无显著差异（腮腺平均标准化摄取值对照组为5.57，干预组为5.72，p = 0.50。下颌下腺平均标准化摄取值对照组为6.25，干预组为5.89，p = 0.12）。4例患者中有3例在使用GPB后唾液腺中的碘摄取增加（每像素平均计数对照组为8.60，干预组为11.46）。
用GPB对唾液分泌进行毒蕈碱抑制并不能显著降低唾液腺中PSMA配体或放射性碘的摄取，因此不能作为降低放射性核素治疗毒性的潜在策略。
