TY - JOUR
T1 - The salivary glands as a dose limiting organ of PSMA- targeted radionuclide therapy: A review of the lessons learnt so far
AU - Heynickx, Nathalie
AU - Herrmann, Ken
AU - Vermeulen, Koen
AU - Baatout, Sarah
AU - Aerts, An
N1 - Score=10
PY - 2021
Y1 - 2021
N2 - At present, prostate cancer remains the second most occurring cancer in men, in Europe. Treatment efficacy for therapy of advanced metastatic disease, and metastatic castration-resistant prostate cancer in particular is limited. Prostate-specific membrane antigen (PSMA) is a promising therapeutic target in prostate cancer, seeing the high amount of overexpression on prostate cancer cells. Clinical investigation of PSMA-targeted radionuclide therapy has shown good clinical efficacy. However, adverse effects are observed of which salivary gland hypofunction and xerostomia are among the most prominent. Salivary gland toxicity is currently the dose-limiting side effect for PSMA-targeted radionuclide therapy, and more specifically for PSMA-targeted alpha therapy. To date, mechanisms underlying the salivary gland uptake of PSMA-targeting compounds and the subsequent damage to the salivary glands remain largely unknown. Furthermore, preventive strategies for salivary gland uptake or strategies for treatment of salivary gland toxicity are needed. This review focuses on the current knowledge on uptake mechanisms of PSMA-targeting compounds in the salivary glands and the research performed to investigate different strategies to prevent or treat salivary gland toxicity.
AB - At present, prostate cancer remains the second most occurring cancer in men, in Europe. Treatment efficacy for therapy of advanced metastatic disease, and metastatic castration-resistant prostate cancer in particular is limited. Prostate-specific membrane antigen (PSMA) is a promising therapeutic target in prostate cancer, seeing the high amount of overexpression on prostate cancer cells. Clinical investigation of PSMA-targeted radionuclide therapy has shown good clinical efficacy. However, adverse effects are observed of which salivary gland hypofunction and xerostomia are among the most prominent. Salivary gland toxicity is currently the dose-limiting side effect for PSMA-targeted radionuclide therapy, and more specifically for PSMA-targeted alpha therapy. To date, mechanisms underlying the salivary gland uptake of PSMA-targeting compounds and the subsequent damage to the salivary glands remain largely unknown. Furthermore, preventive strategies for salivary gland uptake or strategies for treatment of salivary gland toxicity are needed. This review focuses on the current knowledge on uptake mechanisms of PSMA-targeting compounds in the salivary glands and the research performed to investigate different strategies to prevent or treat salivary gland toxicity.
KW - Prostate cancer
KW - PSMA-targeted radionuclide therapy
KW - Salivary gland toxicity
KW - Xerostomia
UR - https://ecm.sckcen.be/OTCS/llisapi.dll/overview/43875932
U2 - 10.1016/j.nucmedbio.2021.04.003
DO - 10.1016/j.nucmedbio.2021.04.003
M3 - Article
SN - 0969-8051
VL - 98-99
SP - 30
EP - 39
JO - Nuclear Medicine and Biology
JF - Nuclear Medicine and Biology
ER -