thorium-227-labeled carboxy-HOPO-PSMA conjugates

Thorium-227-labeled carboxy-HOPO-PSMA conjugates (also known as PSMA SMOL-TTC) are preclinical-stage targeted alpha therapies (TAT) developed by Bayer for the treatment of prostate cancer. These conjugates consist of a prostate-specific membrane antigen (PSMA)-targeting small molecule ligand linked via an optimized spacer to a novel, hydrophilic 2,3-hydroxypyridinone (carboxy-HOPO) chelator, which is complexed with the alpha-emitting radionuclide thorium-227. The carboxy-HOPO chelator features carboxyl groups that increase the hydrophilicity of the conjugate and allow for the attachment of multiple PSMA-binding moieties, enabling the synthesis of monomeric, dimeric, trimeric, and tetrameric variants. Upon binding to PSMA-expressing prostate cancer cells, the conjugates are internalized, delivering high-energy, short-range alpha radiation that induces lethal DNA double-strand breaks in tumor cells while exhibiting rapid blood clearance and low non-specific accumulation in salivary glands and kidneys.

Other names

227Th-Carboxy-HOPO-PSMAPSMA SMOL-TTCthorium-227-labeled carboxy-HOPO-PSMA small molecule conjugatesthorium227-labeled carboxy-HOPO-PSMA small molecule conjugatesthorium 227-labeled carboxy-HOPO-PSMA small molecule conjugatesthorium-227-labelled carboxy-HOPO-PSMA conjugatesthorium227-labelled carboxy-HOPO-PSMA conjugatesthorium 227-labelled carboxy-HOPO-PSMA conjugatesthorium-227-labelled carboxy-HOPO-PSMA small molecule conjugatesthorium227-labelled carboxy-HOPO-PSMA small molecule conjugatesthorium 227-labelled carboxy-HOPO-PSMA small molecule conjugates