Patients must meet the following criteria in order to be included in both the Phase 1 and Phase 2a parts of the trial:

Male and ≥ 18 years

Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features at initial diagnosis

Disease progression on any one of the following: prior enzalutamide, abiraterone, apalutamide or related agent therapy as defined by meeting at least one of the following criteria per the investigator in accordance with the Prostate Cancer Working Group 3 (PCWG3) criteria \[Scher et al, 2016\]: 1. PSA progression as defined by a minimum of two rising PSA levels at least 1 week apart, ideally three successive measurements 2. Soft tissue disease progression defined as \>20% increase in sum of diameters of all target lesions based on sum of diameters since treatment started or the appearance of 1 or more new lesions by RECIST 1.1 3. Bone disease progression defined by two or more new lesions on bone scan

Serum testosterone level \< 50 ng/dL (\< 0.5 ng/mL, \< 1.7 nmol/L). Patients may have ongoing androgen deprivation therapy (ADT) with a luteinizing hormone-releasing hormone (LHRH) "super-agonist" or antagonist, and/or be surgically or medically castrated.

Patients must have PSMA positive lesions. These are defined as having Ga 68-PSMA-11 uptake greater than that of liver parenchyma in one or more metastatic lesions of any size in any organ system. PSMA-negative lesions are defined as having PSMA uptake equal to or lower than that of liver parenchyma in any lymph node with a short axis of at least 2.5 cm, in any metastatic solid-organ lesions with a short axis of at least 1.0 cm, or in any metastatic bone lesion with a soft-tissue component of at least 1.0 cm in the short axis.

Patients receiving bisphosphonate therapy must have been on stable doses for at least 4 weeks prior to Day 1

Patients who have received a taxane or are ineligible or choose not to receive taxane-based chemotherapy based on personal preference or physician opinion. Examples of conditions that could make a patient ineligible or refuse to receive taxane-based chemotherapy include the following: 1. Poor performance status 2. Prior intolerance to cytotoxic agents 3. Other serious medical conditions such as symptomatic peripheral neuropathy Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or higher; or clinically significant cardiovascular disease per the Investigator

ECOG PS of 0 to 2 for Phase 1 and 0 to 1 for Phase 2a

Estimated life expectancy of at least 3 months for Phase 1 and 6 months for Phase 2a as determined by the Investigator.

For patients who have partners of childbearing potential, the partner and/or patient must use a method of birth control with adequate barrier protection, deemed acceptable by the principal investigator during the study and for 3 months after last study drug administration.

Able and willing to provide signed informed consent and comply with protocol requirements

Minimum age: 18

Patients will be excluded from the study if they meet any of the following criteria (applies to both Phase 1 and Phase 2a):

Impaired organ function as evidenced by the following laboratory values at Screening: 1. Absolute neutrophil count \< 1500/μL 2. Platelet count \< 100,000/μL 3. Hemoglobin \< 9.0 g/dL Note: the patient cannot have received blood transfusion or growth factor support in the 2 weeks prior to screening laboratory hematology assessments. 4. Albumin \< 3.0 g/dL (30 g/L) 5. Total bilirubin \> 2 x upper limit of normal (ULN) unless in instances of known or suspected Gilbert's disease 6. aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 2.5 x ULN 7. Calculated creatinine clearance \< 60 mL/min (Cockroft-Gault equation), or currently on renal dialysi

QT interval corrected for heart rate (QTcF) \> 470 msec

Sjogren's syndrome

Known or suspected brain metastasis or active leptomeningeal disease

History of other malignancy within the previous 3 years, except basal cell or squamous cell carcinoma, or non-muscle invasive bladder cancer

History of active thromboembolism within the last 3 months of Day 1

Serious persistent infection within 14 days prior to Day 1

If the patient is known to have a positive polymerase chain reaction (PCR) test for active COVID-19 infection or signs or symptoms consistent with COVID-19, in the absence of a positive PCR test, within 5 days from date of consent

Patients with any medical condition or other circumstances that, in the opinion of the investigator, compromise obtaining reliable data, achieving study objectives, or completing the study

History of congestive heart failure New York Heart Association (NYHA) class III or IV, uncontrolled hypertension or evidence of coronary artery disease (including a myocardial infarction) within the previous 6 months from date of consent

Patients who received any anti-tumor therapy within 4 weeks of Day 1, with the exception of abiraterone, enzalutamide or apalutamide, GnRH therapy and non-radioactive bone-targeted agents

Superscan as evidenced on baseline bone scan

Treatment with Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223 within 6 months prior to Day 1

Prior hemi-body irradiation

Prior PSMA-targeted radioligand therapy

Major surgery within 4 weeks of Day 1

Prior systemic beta-emitting bone-seeking radioisotopes

Radiation therapy for treatment of prostate cancer within 4 weeks of Day 1

Use of anticoagulants within 3 months prior to Day 1 for patients with a history of thromboembolic conditions. Note: Patients receiving anticoagulants for atrial fibrillation are eligible for the study so long as they are on a stable dose of anticoagulants

Prior use of any herbal products known to decrease PSA levels (e.g., PC-SPES \[prostate cancer hope - dietary supplement\] or saw palmetto) within 30 days prior to Day 1

Planned initiation of alternative therapy for prostate cancer, investigational therapy, or participation in clinical trials during the study

Known history of human immunodeficiency virus (HIV) hepatitis B or C infection: 1. HIV infected patients who are healthy and have a low risk of Acquired Immune Deficiency Syndrome (AIDS)-related outcomes will be included. 2. Patients with a history of hepatitis B or C will be allowed to enrol if hepatitis B virus (HBV) DNA or hepatitis C virus (HCV) RNA are undetectable. At this early stage of development, about the main concern is the potential for re-activation or worsening of HBV or HCV from the effect of radiation on lymphocyte function

Vulnerable patients (the investigator involved in the study or his/her family, research staff or students of the investigator involved in the study)

Implantation of investigational medical device within 4 weeks of Day 1 or current enrolment in oncologic investigational drug or device study

Use of investigational drugs within 4 weeks or less than 5 half-lives of Day 1

Patients are excluded if treatment other than the treatment provided in this study is determined more appropriate as determined by the investigator based on the patient and disease characteristics