This is a pilot study of single dose of 225Ac-J591 at 90 KBq/Kg in men with progressive metastatic castration resistant prostate cancer (mCRPC).

This research study is being done because the standard treatments for prostate cancer that has spread beyond the prostate gland are intended to minimize the adverse effects of the disease and make men live longer. These treatments, however, are not curative so additional treatments are needed. Prostate-specific membrane antigen (PSMA) is a protein that is on the surface of most prostate cancer cells. It is absent from most other normal places in the body, but is present to some degree in the kidney, small intestine, salivary glands, and brain. J591 is a monoclonal antibody (an engineered protein) which recognizes PSMA. Actinium-225 (225Ac) is a small radioactive particle that emits alpha-particles (damaging/ionizing radiation). 225Ac-J591 is the combination compound that has the radioactive particle linked to J591. It is designed so that J591 will recognize PSMA and drags the radioactive particle 225Ac with it wherever it goes. This drug used currently is not approved by the U.S. Food and Drug Administration (FDA) approved for any indication and is considered experimental.
   
In the first part of the study, a small group of participants will receive a dose of 225Ac-J591 based upon a prior study. If that dose does not lead to severe side effects, an additional small group will be treated. If the initial dose leads to too many severe side effects, another group will receive a lower dose. If it is determined by a physician that a participant's tumor has responded favorably to treatment, they did not experience severe side effects, and they are in agreement, then the participant will be allowed to receive one additional dose of the study drug 225Ac-J591, provided that at least 3 months have passed since the initial dose.

For participants receiving re-treatment, they will also participate in the same study procedures and followed for treatment including short-term and long-term follow up.

The treatment portion of this study will last approximately 3 months, with follow up for all patients as determined by the study team.