Clinical Research Directory

* INCLUSION CRITERIA: * Histopathological confirmation of prostate adenocarcinoma confirmed in either the Laboratory of Pathology at the National Institutes of Health (NIH) Clinical Center, or Walter Reed National Military Medical Center prior to enrollment. If no pathologic specimen is available, participants may enroll with a pathologist s report showing a histologic diagnosis of prostate cancer and a clinical course consistent with the disease. * Biochemical progression after definitive surgery or radiation define as follows: * Participants must have a detectable PSA * Negative CT scan/MRI and Tc99 bone scan for metastatic prostate cancer. (Only Tc99 will be used to detect bone lesions, CT/MRI would be used to detect soft tissue lesions) * Presence of findings on PET scan (i.e., NaF PET scan) suspicious for metastatic prostate cancer in bone. Note: while lymph node findings would be allowed and provide the opportunity for the assessment of any abscopal effects, PET scan findings suggesting visceral disease will be excluded. * Testosterone \>= 100 ng/dL * ECOG performance status of 0 1 * Recovery from acute toxicity related to prior therapy, including surgery and radiation, (defined as no toxicity \>= grade 2). * Hematological eligibility parameters (within 16 days before treatment initiation): * Granulocyte count \>= 3,000/mm\^3 * Absolute neutrophil count (ANC) \>= 1,500/mm\^3 * Platelet count \>= 100,000/mm\^3 * Hgb \>= 10 g/dL * Hepatic function eligibility parameters (within 16 days before treatment initiation) \-- Bilirubin \<=1.5 mg/dL (OR in participants with Gilbert s syndrome, a total bilirubin \<= 3.0), AST and ALT \<= 2.5 times upper limit of normal. * Adequate renal function defined by eGFR within normal as predicted by the CKD-EPI equation (\>= 50 mL/min/1.73m\^2) or by measure o f creatinine clearance from 24-hour urine collection. * No other active malignancies within 36 months of treatment initiation (with the exception of nonmelanoma skin cancers or carcinoma in situ of the bladder) * Participants must be \>=18 years old. Currently, no dosing or adverse event data is available on the use of radium in participants \< 18 years of age; therefore, only adults are included in this study. * Ability of subject to understand and the willingness to sign a written informed consent document. * The effects radium-223 on the developing human fetus are unknown but based on the mechanism of action, radium-223 has the potential to cause fetal harm. For this reason, men must agree to use condoms for the duration of study therapy and at least 6 months after the last treatment administration. Female partners of reproductive potential must use a highly effective method of birth control during treatment and for 6 months after their partner s last treatment administration. Should a woman become pregnant or suspect she is pregnant while her partner is participating in this study, she should inform her treating physician immediately. EXCLUSION CRITERIA: * Participants with immunocompromised status due to Human Immunodeficiency Virus (HIV) infection or other immunodeficiency diseases because this is a trial with a primary endpoint looking at immune response, requiring functional immune systems. * Participants who test positive for HBV or HCV. * Chronic administration (defined as daily or every other day for continued use \> 14 days) of systemic corticosteroids within 28 days of treatment initiation. Use of corticosteroids with minimal systemic absorption (e.g., inhaled steroids, nasal sprays, intraarticular, and topical agents) is allowed. * Receipt of any organ transplantation, including allogeneic stem-cell transplantation, but with the exception of transplants that do not require immunosuppression (e.g. corneal transplant, hair transplant). * Serious intercurrent medical illness that, in the judgement of the investigator, would interfere with participant's ability to carry out the treatment program. * Subjects required other medications known to alter PSA including 5-alpha reductase inhibitors (finasteride and dutasteride) and alternative therapies (e.g., phytoestrogens and saw palmetto). * History of prior chemotherapy. * History of prior systemic therapy with radionuclides (e.g., strontium-89, samarium-153, rhenium-186, rhenium-188, or radium 223 dichloride). * Receipt of an investigational agent within 28 days (or 56 days for an antibody-based therapy) of treatment initiation. * Major surgery within 28 days prior to treatment initiation. * PET scan findings suggesting visceral disease.