psma-617 and Neoplasm-Metastasis

Metastatic castration-resistant prostate cancer (mCRPC) remains a terminal diagnosis with an aggressive disease course despite currently approved therapeutics. The recent successful development of poly ADP-ribose polymerase (PARP) inhibitors for patients with mCRPC and mutations in DNA damage repair genes has added to the treatment armamentarium and improved personalized treatments for prostate cancer. Other promising therapeutic agents currently in clinical development include the radiotherapeutic 177-lutetium-prostate-specific membrane antigen (PSMA)-617 targeting PSMA-expressing prostate cancer and combinations of immunotherapy with currently effective treatment options for prostate cancer. Herein, we have highlighted the progress in systemic treatments for mCRPC and the promising agents currently in ongoing clinical trials.

Topics: Androgen Receptor Antagonists; Animals; Antineoplastic Agents; Clinical Trials as Topic; Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Lutetium; Male; Neoplasm Metastasis; Poly(ADP-ribose) Polymerase Inhibitors; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radioisotopes

Progressive metastatic castration-resistant prostate cancer is a highly lethal disorder and new effective therapeutic agents that improve patient outcomes are urgently needed. Lutetium-177 [. Between Aug 26, 2015, and Dec 8, 2016, 43 men were screened to identify 30 patients eligible for treatment. 26 (87%) had received at least one line of previous chemotherapy (80% docetaxel and 47% cabazitaxel) and 25 (83%) received prior abiraterone acetate, enzalutamide, or both. The mean administered radioactivity was 7·5 GBq per cycle. 17 (57%) of 30 patients (95% CI 37-75) achieved a PSA decline of 50% or more. There were no treatment-related deaths. The most common toxic effects related to [. Our findings show that radionuclide treatment with [. None.

Topics: Aged; Dipeptides; Disease Progression; Health Status; Heterocyclic Compounds, 1-Ring; Humans; Kallikreins; Lutetium; Male; Neoplasm Metastasis; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Quality of Life; Radioisotopes; Radiopharmaceuticals; Time Factors; Treatment Outcome; Victoria

Beta-emitting Lu-177-labeled prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) is a new option for metastatic castration-resistant prostate cancer (mCRPC), but its antitumor effect can decrease over time.. To report the safety and activity of alpha-emitting Ac-225-PSMA-617 RLT in mCRPC that has progressed after Lu-177-PSMA.. Twenty-six patients were treated under a compassionate use protocol. The eligibility criteria included previous treatment with abiraterone or enzalutamide, previous taxane-based chemotherapy, progression after Lu-177-PSMA, and positive PSMA-ligand uptake. The median number of previous mCRPC regimens was 6. Ac-225-PSMA-617 was given every 8 wk until progression/intolerable side effects.. Prostate-specific antigen (PSA) decline, PSA progression-free survival (PSA-PFS), clinical progression-free survival (cPFS), overall survival (OS), and toxicity were measured.. Sixty-one cycles of Ac-225-PSMA-617 (median number of cycles 2; median activity 9 MBq) were administered. A PSA decline of ≥50% was achieved in 17/26 patients. The median PSA-PFS, cPFS, and OS periods were 3.5 (95% confidence interval [CI] 1.8-11.2), 4.1 (95% CI 3-14.8), and 7.7 (95% CI 4.5-12.1) mo, respectively. Liver metastases were associated with shorter PSA-PFS (median 1.9 vs 4.0 mo; p = 0.02), cPFS (median 1.8 vs 5.2 mo; p = 0.001), and OS (median 4.3 vs 10.4 mo; p = 0.01). Hematological grade 3/4 toxicities were anemia (35%), leucopenia (27%), and thrombocytopenia (19%). All patients experienced grade 1/2 xerostomia. Two and six patients stopped due to hematological toxicity and xerostomia, respectively. A limitation is the retrospective design.. Ac-225-PSMA-617 showed measurable antitumor effect after Lu-177-PSMA failure in late-stage mCRPC. Grade 3/4 hematological side effects were observed in up to one-third of patients, and xerostomia led to treatment halt in a relevant number of patients.. Ac-225-labeled prostate-specific membrane antigen (PSMA)-617 therapy showed substantial antitumor effect in late metastatic castration-resistant prostate cancer after Lu-177-PSMA failure. However, dry mouth is a common side effect that caused about a quarter of patients to stop therapy.

Topics: Actinium; Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Lutetium; Male; Neoplasm Metastasis; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radioisotopes; Radiopharmaceuticals; Retrospective Studies; Treatment Outcome; Xerostomia

PSMA-based radioligand therapies have shown the beneficial effect in metastatic castrate-resistant prostate cancer (mCRPC) patients when they become refectory to the established treatments with associated potential toxicities and high mortality rate. Ac-PSMA therapy is known to be remarkably effective in substantially pretreated mCRPC patients. However, posttherapy imaging is usually not performed as alpha emitters are really difficult to image. We presents a patient of mCRPC treated with Ac-PSMA-617, and his posttherapy whole-body scans acquired by using 3 different photopeaks (78, 218, and 440 keV) fairly demonstrated the tracer's distribution and the efficacy of targeted alpha therapy.

Topics: Actinium; Alpha Particles; Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Ligands; Male; Neoplasm Metastasis; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant

[Sc]Sc-PSMA-617 with 3.9-hour half-life, in vitro and in vivo characteristics similar to [Lu]Lu-PSMA-617 and possibility of delayed imaging after 24 hours or later, implies it to be advantageous than [ Ga]Ga-PSMA-617 for pretherapeutic dosimetric assessment for [Lu]Lu-PSMA-617 in metastatic castration-resistant prostate carcinoma (mCRPC) patients. In this study, we investigated biodistribution and radiation exposure to normal organs with [Sc]Sc-PSMA-617 in mCRPC patients.. Five mCRPC patients (mean age, 69 years) enrolled for [Lu]Lu-PSMA-617 therapy were injected with 40-62 MBq [Sc]Sc-PSMA-617 intravenously; Siemens Biograph 2 PET/CT system was used to acquire dynamic PET data (30 minutes) in list mode over the abdomen, followed by the collection of static PET/CT images (skull to mid-thigh) at 45 minutes, 2 and approximately 20 hours postinjection. Time-dependent changes in percentage activity in source organs (kidneys, bladder, salivary glands, small intestine, liver, spleen, and whole body) were determined. Bone marrow and urinary bladder contents residence time were also calculated. Source organs residence time, organ-absorbed doses, and effective doses were determined using OLINDA/EXM software.. Physiological tracer uptake was seen in kidneys, liver, spleen, small intestine, urinary bladder, and salivary glands and in metastases. Kidneys with highest radiation absorbed dose of 3.19E-01 mSv/MBq were the critical organs, followed by urinary bladder wall (2.24E-01 mSv/MBq, spleen [1.85E-01], salivary glands [1.11E-01], and liver [1.07E-01] mSv/MBq). Red marrow dose was found to be 3.31E-02 mSv/MBq. The mean effective dose of 3.89E-02 mSv/MBq and effective dose of 1.95 mSv was estimated from 50 MBq (treatment planning dose) of [Sc]Sc-PSMA-617.. [Sc]Sc-PSMA-617 is found to be a very promising radiopharmaceutical that can be used for pre [Lu]Lu-PSMA-617 therapeutic dosimetric assessment.

Topics: Aged; Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Male; Neoplasm Metastasis; Positron Emission Tomography Computed Tomography; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radiation Dosage; Radioisotopes; Radiopharmaceuticals; Scandium; Tissue Distribution

[. Fifty-five patients with castrate-resistant metastatic prostate cancer treated with at least three cycles of [. None of the 55 patients experienced severe nephrotoxicity (grade 3/4). In 14 patients (25%), we observed increased creatinine levels of CTC 1° or 2°. There were 16 cases of increased GFR (grade 1/2). At the baseline, only 14 patients had elevated cystatin C. However, post-therapeutic cystatin C was elevated in 32 patients (58%). A significant effect on renal function was found for age (p = 0.049), hypertension (p = 0.001) and pre-existing kidney disease (p = 0.001). The most reliable predictive markers of nephrotoxicity were TER-MAG3 and cystatin C.. Renal toxicity in patients treated with [

Topics: Aged; Dipeptides; Heterocyclic Compounds, 1-Ring; Hormones; Humans; Kidney; Ligands; Lutetium; Male; Neoplasm Metastasis; Prostate-Specific Antigen; Prostatic Neoplasms; Radioisotopes; Risk Factors; Time Factors; Treatment Failure

Topics: Alpha Particles; Bismuth; Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Male; Molecular Targeted Therapy; Neoplasm Metastasis; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radioisotopes

An 80-year-old patient with castrate-resistant prostate cancer presented to our department for PSMA imaging because of a rising prostate-specific antigen (PSA) level. The tumor was diagnosed in 2004. GnRh analog was the only treatment the patient received. Two cycles of Lu-PSMA-617 were performed with a 2-month interval in between. Ten months after finishing with 2 cycles of Lu-PSMA therapy, we noticed a continuous falling PSA level and a decreasing tumor spread in the PET/CT imaging just under the hormone therapy.

Topics: Aged, 80 and over; Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Lutetium; Male; Neoplasm Metastasis; Positron Emission Tomography Computed Tomography; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radioisotopes; Treatment Outcome

Topics: Antigens, Surface; Awards and Prizes; Baltimore; Dipeptides; Gallium; Glutamate Carboxypeptidase II; Heterocyclic Compounds, 1-Ring; History, 21st Century; Humans; Lutetium; Male; Neoplasm Metastasis; Nuclear Medicine; Prostate-Specific Antigen; Prostatic Neoplasms; Radioisotopes; Radionuclide Imaging; Societies, Medical