Project objectives

The main objective of the project is in vitro and in vivo evaluation of anti-PSMA-functionalized NaA nanozeolites labeled with the alpha-emitter 223Ra as a new radio-immunoconjugate for targeted therapy of prostate cancer.

This will be achieved by pursuing the following sub-goals:

• Synthesis and physicochemical characterization of anti-PSMA-functionalized NaA nanozeolites labeled with the alpha-emitter 223Ra.

• Analysis of in vitro toxicity of unlabeled anti-PSMA-functionalized NaA nanozeolites and NaA nanozeolites as carriers with emphasis on cytotoxicity, inflammation and oxidative stress in human prostate cancer cells and normal prostate cells.

• Assessment of in vitro efficacy of anti-PSMA-functionalized NaA nanozeolites labeled with the alpha-emitter 223Ra and NaA nanozeolites labeled with the alpha-emitter 223Ra with emphasis on binding affinity to PSMA receptors, ability to inhibit migration/invasion of prostate cancer cells and induction of DNA double strand breaks.

• Preclinical pharmacokinetics and toxicity studies of NaA nanozeolite functionalized with anti-PSMA antibodies and labeled with barium-133 and radium-223 radioisotopes in normal mice.

• Analysis of localization in vivo and biodistribution ex vivo of NaA nanozeolite functionalized with anti-PSMA antibodies and labeled with radium-223 and barium-133 radioizotope and NaA nanozeolite labeled with barium radioizotope as emitter of beta particles in murine model of human prostate cancer.