Abstract
Despite multiple new agents having been available routinely for men with
metastatic castration-resistant prostate cancer (mCRPC), the diagnosis remains fatal,
with these agents contributing minimally to over-all survival. Targeting the prostatespecific
membrane antigen (PSMA) has been attractive because it is overly expressed
in prostate cancer cells with upregulation of the over-expression related to tumour
grade, castration status and metastatic disease. To this end novel agents have been
developed targeting the PSMA antigen not only for imaging but also for therapy.
Actinium-225 (225Ac), an alpha emitter, has been labelled to PSMA ligands as 225Ac-
PSMA for targeted alpha therapy (TAT). 225Ac deposits high energy, resulting in
irreparable double strand DNA destruction while sparing surrounding normal tissue,
making it an attractive anti-tumour agent. Clinical application of 225Ac-PSMA TAT as
the last line of therapy in patients with mCRPC has demonstrated an excellent
response, especially in the setting of chemotherapy-naive patients. Widespread
application of 225Ac-PSMA TAT, though remains hampered by its salivary gland
toxicity.
Keywords: 225Ac-PSMA, mCRPC, Prostate Cancer, Targeted Alpha Therapy, Theranostics.
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