Injection with botulinum toxin (BTX) type A (IncoA) plus transdermal scopolamine led to the reduction in radiation-induced salivary gland toxicity without compromising PSMA (prostate-specific membrane antigen) tumor uptake in patients with metastatic prostate cancer who were receiving radiopharmaceuticals. These findings were presented at the 2025 Society of Nuclear Medicine and Molecular Imaging Annual Meeting (Abstract 251452).
“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 study author 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 [actinium-225].”
Study Methods and Rationale
Although PSMA-targeted radioligand therapy has made a big impact on treatment for patients with advanced or metastatic castration-resistant prostate cancer, salivary gland toxicity is a major dose-limiting adverse effect. Severe dry mouth is often seen with alpha-emitting radionuclides, such as actinium-225, which is used in tandem radioligand therapy with actinium-225 and 177-Lu–PSMA-targeted treatment. Previous research has looked at improving this toxicity with cold packs, single anticholinergics, or external cooling, but minimal benefit has been seen.
“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 lead study author 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.”
The study included 14 patients who received injections of BTX IncoA prior to tandem radioligand therapy. One patient received two injections prior to radioligand therapy, and one patient received BTX injections prior to each of two cycles of tandem radioligand therapy, for a total of 16 injections. Four patients received BTX alone, and the other 10 patients received BTX plus scopolamine.
Up to 250 units of BTX IncoA was injected percutaneously in one parotid gland and the contralateral submandibular glands under ultrasound control 3 to 4 weeks prior to scheduled radioligand therapy. Transdermal scopolamine patches were placed behind the ears 72 hours before tandem radioligand therapy and were removed 2 hours after.
Key Study Findings
A significant reduction in PSMA radioligand uptake was observed in the parotid gland (P < .001) and contralateral submandibular glands (P = .004) for those receiving IncoA. Patients treated with BTX had a mean 30% reduction in PSMA uptake in the parotid glands (range, 19%–47%) compared with the opposite parotid gland. One patient did not respond to treatment. A mean 17% reduction in PSMA uptake (range, 10%–51%) was reported for injected submandibular glands vs the opposite submandibular glands.
According to the study investigators, all injections were well tolerated, with patients reporting mild injection pain but no serious or systemic adverse effects, and no grade 3 or 4 toxicities were observed. One injection-related local hematoma was reported in a patient with thrombocytopenia. No patient discontinued PSMA tandem therapy because of xerostomia. Transdermal scopolamine-induced moderate dry mouth lasted for the 72 hours of application.
Disclosure: For full disclosures of the study authors, visit jnm.snmjournals.org.
