Actium-225-Prostate Specific Membrane Antigen Imaging & Therapy

Inclusion Criteria:

• Histopathological proven metastatic castration resistant prostate cancer.Castrationresistant disease is defined as a serum testosterone level of 50 nanogramper deciliter or lower (≤1.7 nanomol per liter) after bilateral orchiectomy or duringmaintenance treatment consisting of androgen-ablation therapy with a luteinizinghormone-releasing hormone agonist.
• Evidence of progressive disease, defined as 1 or more Prostate Cancer Work Grouping 3 (PCWG3) criteria: - PSA level ≥ 1 ng/mL that has increased on at least 2 successiveoccasions at least 1 week apart
• Progression as defined by RECIST 1.1 with PCGW3 modifications
• Progression after at least one line of chemotherapy and/or one line of nonsteroidalantiandrogen (NSAA).
• No active anti-tumor therapy, except for androgen deprivation therapy in combinationwith at least one androgen receptor-targeted agent
• Willing and able to undergo 2 cycles of 225Ac-PSMA I&T therapy and 3 PET-MRI scans in 16 weeks and comply with protocol
• Signed and dated written informed consent by the patient (or legal representative)prior to any study-specific procedures.
• Age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance-status score 0-2.
• Use of highly effective methods of contraception (female partners of maleparticipants)
• During the trial and 6 months after completion of the study or willing to practicesexual abstinence.

Exclusion Criteria:

• Concurrent severe illness or clinically relevant trauma within 2 weeks before theadministration of the investigational product that might preclude study completion orinterfere with study results
• Serum hemoglobin ≤ 6.2 mmol/L, total white blood cell (WBC) count ≤ 3.5·109/L,absolute neutrophil count ≤ 1.5·109/L, platelet count ≤ 100·109/L, serum creatinineconcentration ≥ 150 umol/L (≥ 1.7 mg/dL), serum albumin <30 g/L, bilirubin ≥ 1.5 xupper limit normal (ULN), aspartate transaminase (ASAT) ≥ 3 x ULN and alanineaminotransferase (ALAT) ≥ 3 x ULN (or bilirubin ≥ 3 x ULN, ASAT ≥ 5 x ULN and ALAT ≥ 5x ULN in the case of pre-existing liver metastases at baseline)
• Concurrent bladder outflow obstruction or unmanageable urinary incontinence
• Known or expected hypersensitivity to Gallium-68, Actinium-225, PSMA I&T, or anyexcipient present in 225Ac/68Ga-PSMA I&T
• Prior administration of a radiopharmaceutical within a period corresponding to 8halflives of the radionuclide used on such radiopharmaceutical
• Prior treatment with any radionuclide therapy
• History of somatic or psychiatric disease/condition that may interfere with theobjectives and assessments of the study
• Central nervous system (CNS) metastases, leptomeningeal disease, or spinal cordcompression
• Radiation therapy within 4 weeks of first dose (or local or focal radiotherapy within 2 weeks of first dose)
• Male subjects unwilling to abstain from donating sperm during treatment and for anadditional 6 months after the last dose