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2022 CRIS Cancer Foundation and Clay Hamlin – PCF Young Investigator Award

Investigating Radiohybrid PSMA-Ligands for Targeted Alpha Therapy, with the Aim to Improve Targeted Alpha Therapy of Metastatic Castration-Resistant Prostate Cancer

Alexander Wurzer, PhD
Technical University of Munich

Description:

  • Molecular radiotherapy is a new class of treatment for prostate cancer, which include the recently FDA-approved treatment, LuPSMA.
  • This type of treatment consists of a radioactive isotope attached to a tumor-targeting molecule, which brings radiation directly to tumors anywhere in the body.
  • However, LuPSMA is not curative, and more optimization is needed.
  • LuPSMA uses beta particle-emitting radioisotopes.
  • Alpha particle-emitters such as 225 Actinium-PSMA are more potent, and a promising option for improving the efficacy of molecular radiotherapy. However, some severe toxicities including salivary gland toxicity, have been anecdotally reported with 225 Actinium-PSMA, and long-term outcomes and side effects have yet to be rigorously studied.
  • Dr. Alexander Wurzer is studying the radioactive properties of 225Actinium-PSMA in the body.
  • Dr. Wurzer will develop “radiohybrid” tool compounds, which allow PET imaging but use non-radioactive metals that chemically mimic the properties of Actinium, to predict the biodistribution of 225 Actinium-PSMA in patients.
  • These radiohybrid compounds will be studied in animal models to estimate where in the body 225 Actinium-PSMA and the daughter isotopes produced during radioactive decay, may accumulate over time.
  • If successful, this data will help to predict the accumulation of 225Actinium-PSMA radioactivity in sensitive organs, such as salivary glands and kidneys, and predict long term toxicities. This data can be used to guide the establishment of optimal radiation doses and treatment protocols of 225Actinium-PSMA, to minimize side effects.

What this means to patients: Alpha-particle emitting molecular radioligand therapies are experimental treatments that require further optimization to limit toxicities. Dr. Wurzer and team will investigate the radioactive properties of these compounds in animal models, in order to understand where radioactivity will accumulate over time, and what organs would be affected. This will help to optimize dosing and treatment protocols, to reduce toxicity and maximize the efficacy of these promising treatments.