PSMA PET-guided protective strategies against radiation therapy induced salivary gland toxicity

This thesis explores the innovative application of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging, traditionally used for prostate cancer staging, to assess salivary gland toxicity from radiation therapy and develop strategies to mitigate it. Radiotherapy, a cornerstone in cancer treatment, often results in unavoidable exposure of healthy tissues to radiation, leading to toxicity. The salivary glands are highly sensitive to radiation and can suffer damage, manifesting as xerostomia or dry mouth, significantly affecting patients' quality of life. Traditional methods for evaluating salivary gland damage are unreliable, necessitating more precise evaluation techniques.
The thesis presents a case series highlighting the variability in PSMA uptake patterns in patients treated with ¹³¹I therapy for thyroid cancer, underscoring the modality's ability to reveal functional variations undetectable by traditional methods. Further, it investigates potential protective strategies against salivary gland toxicity in radionuclide therapy, notably evaluating the effects of glycopyrronium bromide (GPB) and gustatory stimulation on PSMA uptake. Interestingly, GPB did not reduce PSMA-ligand or ¹³¹I uptake, while eating or gustatory stimulation was advised against during therapy due to its potential to exacerbate PSMA uptake.
The research also outlines the derivation of dose-response curves for salivary glands from external beam radiotherapy using PSMA PET, and suggests an optimization path for reducing toxicity further. This thesis signifies a significant step forward in utilizing functional imaging for toxicity evaluation and treatment optimization in cancer therapy, opening avenues for its application in other normal tissues.