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Sublingual Atropine Administration as a Tool to Decrease Salivary Glands' PSMA-Ligand Uptake: A Preclinical Proof of
Vincent Nail1,2,3, Béatrice Louis1,3, Anaïs Moyon1,2,3
1Centre Européen de Recherche en Imagerie Médicale (CERIMED), Aix-Marseille University, CNRS, 13005 Marseille, France.
Pharmaceutics
|June 24, 2022
Summary
Atropine can reduce salivary gland uptake during prostate cancer imaging and therapy. This preclinical study found sublingual atropine significantly decreased radiotracer uptake in salivary glands, offering a potential strategy to mitigate treatment side effects.
Area of Science:
- Nuclear Medicine
- Oncology
- Pharmacology
Background:
- Prostate Specific Membrane Antigen (PSMA)-directed radionuclide therapy is crucial for advanced prostate cancer.
- Treatment toxicities, like xerostomia (dry mouth), particularly with alpha emitters, necessitate preventive strategies.
- Salivary gland uptake of radiotracers can limit treatment efficacy and increase side effects.
Purpose of the Study:
- To evaluate the efficacy of alpha-adrenergic and anticholinergic drugs in reducing salivary gland uptake of radiotracers.
- To identify a potential strategy for mitigating xerostomia associated with PSMA-targeted therapies.
Main Methods:
- Preclinical evaluation in mice using [99mTc]TcO4− SPECT/CT to assess drug effects on salivary glands.
- Testing phenylephrine, scopolamine, atropine, and ipratropium.
- Further evaluation of the most effective drug using [68Ga]Ga-PSMA-11 PET/CT in both non-tumor-bearing and xenografted mice.
Main Results:
- Scopolamine and atropine significantly reduced parotid gland uptake on SPECT/CT.
- Phenylephrine and ipratropium showed no significant effect.
- Sublingual atropine demonstrated the greatest efficacy, decreasing [68Ga]Ga-PSMA-11 uptake by 51.6% in parotids of non-tumor-bearing mice and 26.8% in xenografted mice.
Conclusions:
- Local administration of atropine is a promising, simple, and safe approach to reduce salivary gland uptake.
- This strategy could potentially mitigate xerostomia in patients undergoing PSMA-targeted radionuclide therapy.
- Further clinical investigation is warranted to confirm these findings in humans.
