image: Figure 1. Salivary gland protection with botulinum toxin and scopolamine during tandem PSMA-targeted radioligand therapy.
Pre-treatment 68Ga-PSMA PET/CT demonstrated comparable tracer uptake in both parotid and submandibular glands. The patient subsequently received ultrasound-guided botulinum toxin injections (170 units in the parotid gland and 80 units in the contralateral submandibular gland) 30 days prior to TANDEM radioligand therapy, along with 3 mg transdermal scopolamine applied 72 hours before treatment. Post-injection SPECT/CT images revealed a marked reduction in PSMA radioligand uptake in the BTX-treated glands, with parotid gland uptake ratio shifting from 0.93 to 1.15 and submandibular gland ratio from 1.39 to 2.14, confirming targeted protection. The patient tolerated both the intervention and the subsequent PRLT (6.2 GBq 177Lu-PSMA and 5 MBq 225Ac-PSMA) without xerostomia or other significant side effects.
Credit: Images created by Tianzhi Zhao, Jingjing Zhang, et al., National University of Singapore, Singapore / Richard P. Baum et al., Curanosticum Wiesbaden-Frankfurt, Wiesbaden, Germany.
NEW ORLEANS— A dual-protective approach using botulinum toxin (Botox) alongside an anti-nausea patch significantly reduces salivary gland toxicity in patients with metastatic prostate cancer undergoing PSMA-targeted radiopharmaceutical therapy. The strategy led to a 30 percent decrease in PSMA uptake by the salivary glands without affecting the treatment’s cancer-fighting efficacy. This reduction may enhance treatment adherence and improve overall patient outcomes. The findings were presented at the Society of Nuclear Medicine and Molecular Imaging 2025 Annual Meeting.
Salivary gland toxicity from radiopharmaceutical therapy—particularly from alpha-emitting therapies like 225Ac-PSMA—is a critical dose-limiting side effect, often leading to debilitating dry mouth. Prior attempts to alleviate dry mouth using cold packs, single anticholinergics, or external cooling have shown minimal protective benefit.
“In order for patients to maintain a good quality of life and continue with their treatments, it’s essential to address these serious dry mouth issues,” said Tianzhi Zhao, research assistant at the Theranostics Centre of Excellence in the Yong Loo Lin School of Medicine at the National University of Singapore. “Our study explored the use of Botox paired with a nausea patch on reducing radiation uptake to the salivary glands.”
Fourteen patients were enrolled in the study and received Botox injections in the parotid and submandibular glands on opposite sides of the body three to four weeks prior to their combined 225Ac- and 177Lu-PSMA radiopharmaceutical therapy. Three days before treatment, nausea patches were applied behind the ears where they remained until two hours after the treatment. Molecular imaging was performed pre- and post-treatment to measure salivary gland uptake.
A significant reduction in PSMA radioligand uptake in the salivary glands was observed. Botox-treated parotid glands showed a mean 30 percent reduction in PSMA uptake compared to the opposite parotid gland. A mean 17 percent reduction in PSMA uptake was observed in injected submandibular glands compared to the opposite submandibular glands. The injections were well tolerated, with patients reporting mild injection pain but no serious or systemic side effects. No patient discontinued PSMA therapy due to dry mouth.
“This study demonstrates that Botox, administered at recommended doses in combination with a nausea patch, offers a promising therapeutic strategy for reducing radiation-induced salivary gland toxicity without compromising PSMA tumor uptake,” stated Jingjing Zhang, MD, PhD, assistant professor at the Theranostics Centre of Excellence in the Yong Loo Lin School of Medicine at the National University of Singapore. “The significance of this work lies in its direct patient benefit and its potential to expand the therapeutic utility of PSMA radiopharmaceutical therapy, particularly with alpha-emitting radionuclides like 225Ac.”
Both Botox and nausea patches are FDA-approved medications, already available in clinical practice for other indications. As this approach leverages approved medications with established safety profiles, this strategy could be immediately applied in experienced centers offering PSMA radioligand therapy.
Abstract 251452. “Botulinum Toxin Plus Scopalamine as a Protective Strategy Against Salivary Gland Toxicity in Patients Treated with 225Ac- and 177Lu- PSMA-Targeted Radioligand Therapy (TANDEM PSMA-RLT),” Tianzhi Zhao and Jingjing Zhang, National University of Singapore; Joerg Mueller, Vivantes Klinikum Spandau; Xin Fan, Nanjing Drum Tower Hospital; and Vivianne Jakobsson and Richard Baum, Curanosticum Wiesbaden-Frankfurt.
Link to Abstract
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All 2025 SNMMI Annual Meeting abstracts can be found online.
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Journal
Journal of Nuclear Medicine
Article Title
Botulinum Toxin Plus Scopalamine as a Protective Strategy Against Salivary Gland Toxicity in Patients Treated with 225Ac- and 177Lu- PSMA-Targeted Radioligand Therapy (TANDEM PSMA-RLT)