psma-617 and Prostatic-Neoplasms--Castration-Resistant

Radionuclide therapy using the small molecule PSMA bound to the beta-emitting radionuclide, Lutetium-177 (

Topics: Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radioisotopes; Radiometry; Radiopharmaceuticals

Actinium-225-labeled prostate-specific membrane antigen ([. A total of 106 patients were included. Skeletal metastasis was in the superscan pattern in 34 patients (32.1%) and multifocal in 72 patients (67.9%). The median treatment cycle was 4 (range = 1-9). Ninety-eight patients (92.5%) had abnormal baseline hematologic parameters. One patient had grade 4 thrombocytopenia. Grade 3 anemia, leukopenia, and thrombocytopenia were seen in 1 (0.9%), 3 (2.8%), and 2 (1.9%) patients, respectively. Age, the number of treatment cycles, and the presence of renal dysfunction were significant predictors of hematologic toxicity. Eighty-five patients (80.2%) achieved PSA response. The median PFS and OS of the study population were 14:00 (95%CI: 8.15-19.86) months and 15.0 (95%CI: 12.8-17.2) months, respectively.. [

Topics: Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Kidney Diseases; Lutetium; Male; Positron Emission Tomography Computed Tomography; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radiopharmaceuticals; Retrospective Studies; Thrombocytopenia; Treatment Outcome

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

Prostate cancer patients with locoregional lymph node disease at diagnosis (N1M0) still have a limited prognosis despite the improvements provided by aggressive curative intent multimodal locoregional external beam radiation therapy (EBRT) with systemic androgen deprivation therapy (ADT). Although some patients can be cured and the majority of patients have a long survival, the 5-year biochemical failure rate is currently 29-47%. [. The PROQURE-I study is a multicenter prospective phase I study investigating standard of care treatment (7 weeks EBRT and 3 years ADT) complemented with one concurrent cycle (three, six, or nine GBq) of systemic [. This is the first prospective study to combine EBRT and ADT with [. ClinicalTrials, NCT05162573 . Registered 7 October 2021.

Topics: Androgen Antagonists; Bayes Theorem; Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Male; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Quality of Life; Treatment Outcome

In VISION, the prostate-specific membrane antigen (PSMA)-targeted radioligand therapy lutetium-177 [. This multicentre, open-label, randomised, phase 3 trial was conducted at 84 cancer centres in nine countries in North America and Europe. Eligible patients were aged 18 years or older; had progressive PSMA-positive metastatic castration-resistant prostate cancer; an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2; and had previously received of at least one androgen receptor pathway inhibitor and one or two taxane-containing regimens. Patients were randomly assigned (2:1) to receive either [. Between June 4, 2018, and Oct 23, 2019, 831 patients were enrolled, of whom 581 were randomly assigned to the [. [. Advanced Accelerator Applications (Novartis).

Topics: Aged; Androgen Receptor Antagonists; Antineoplastic Combined Chemotherapy Protocols; Humans; Male; Pain; Prostatic Neoplasms, Castration-Resistant; Quality of Life; Receptors, Androgen; Standard of Care; Taxoids

The prostate-specific membrane antigen (PSMA) inhibitor [

Topics: Dipeptides; Docetaxel; Heterocyclic Compounds, 1-Ring; Humans; Lutetium; Male; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radiopharmaceuticals; Retrospective Studies; Survival Analysis; Treatment Outcome

Checkpoint inhibitors have been shown to have limited activity in patients with metastatic castration-resistant prostate cancer. We aimed to determine whether a single dose of lutetium-177 [. We did an open-label, dose-expansion, phase 1 study at the University of California, San Francisco (San Fransisco, CA, USA). Eligible patients were men aged 18 years or older with progressive metastatic castration-resistant prostate cancer who had an Eastern Cooperative Oncology Group performance status of 0 or 1, had progression on one or more androgen signalling inhibitors, and at least three PSMA-avid lesions on. Between Aug 8, 2019 and May 7, 2022, 43 male patients were enrolled (n=18 part A [six patients per schedule]; n=25 part B), with a median follow-up of 16·5 months (IQR 12·2-21·9). Schedule 1 was selected as the recommended phase 2 schedule for part B, on the basis of safety and feasibility of administration observed in part A. In part B, 14 (56%; 95% CI 35-76) of 25 patients had a confirmed objective response. Two (5%) of 43 patients had a treatment-related adverse event of grade 3 or worse (grade 3 arthritis in schedule 2, grade 3 pneumonitis in schedule 3). One serious adverse event (one death due to aspiration pneumonia) and no treatment-related deaths were observed.. A single priming dose of. Prostate Cancer Foundation, National Cancer Institute, Novartis Pharmaceuticals, and Merck.

Topics: Heterocyclic Compounds, 1-Ring; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Treatment Outcome

Previously, results from the TheraP trial showed that treatment with lutetium-177 [. TheraP was a multicentre, open-label, randomised phase 2 trial that recruited men with metastatic castration-resistant prostate cancer after treatment with docetaxel who were suitable for cabazitaxel from 11 hospitals in Australia. Participants were required to be 18 years old or older; have adequate haematological, renal, and liver function; and an Eastern Cooperative Oncology Group performance status of 0-2. Participants were randomly assigned (1:1) using a centralised system using minimisation with a random component and that stratified patients by disease burden, previous treatment with enzalutamide or abiraterone, and study site. Patients were either given cabazitaxel (20 mg/m. In men with metastatic castration-resistant prostate cancer, PSMA-PET SUVmean was predictive of higher likelihood of favourable response to [. Prostate Cancer Foundation of Australia, Endocyte (a Novartis Company), Australian Nuclear Science and Technology Organisation, Movember Foundation, It's a Bloke Thing, CAN4CANCER, The Distinguished Gentleman's Ride.

Topics: Adolescent; Adult; Australia; Fluorodeoxyglucose F18; Humans; Male; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Treatment Outcome

Metastatic castration-resistant prostate cancer remains fatal despite recent advances. Prostate-specific membrane antigen (PSMA) is highly expressed in metastatic castration-resistant prostate cancer. Lutetium-177 (. We conducted an international, open-label, phase 3 trial evaluating. From June 2018 to mid-October 2019, a total of 831 of 1179 screened patients underwent randomization. The baseline characteristics of the patients were balanced between the groups. The median follow-up was 20.9 months.. Radioligand therapy with

Topics: Aged; Aged, 80 and over; Combined Modality Therapy; Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Kallikreins; Lutetium; Male; Middle Aged; Positron-Emission Tomography; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radioisotopes; Survival Analysis

In a Phase 2 clinical trial, we aimed to determine the lutetium-177 [. We determined AR copy number in pretreatment plasma samples. We used logistic regression to estimate the odds ratio (OR) and 95% confidence intervals (95% CIs) in order to evaluate the independent relevance of AR status and to evaluate patients with early progressive disease (PD) defined as treatment interruption occurring within 4 months after the start of. Twelve of the 15 (80%) with AR gene gain and 5 of the 25 (20%) patients with no gain of AR had early PD (p = 0.0002). The OR for patients without PSA response having AR gain was 3.69 (95% CI 0.83-16.36, p = 0.085). The OR for patients with early PD having AR gain was 16.00, (95% CI 3.23-79.27, p = 0.0007). Overall, median PFS and OS were 7.5 and 12.4 months, respectively. AR-gained had a significant shorter OS compared to AR-normal patients (7.4 vs 19.1 months, p = 0.020). No treatment interruptions due to adverse effects were reported.. Plasma AR status helped to indicate mCRPC with early resistance to. NCT03454750.

Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Dipeptides; Drug Resistance, Neoplasm; Gene Amplification; Heterocyclic Compounds, 1-Ring; Humans; Logistic Models; Lutetium; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radioisotopes; Receptors, Androgen; Survival Analysis

Fourteen of 18 men screened underwent Lu-PSMA therapy. Ten (71%) of 14 had a PSA response (mean reduction, 59%). A ≥ 50% reduction in PSA occurred in 5 (36%), and ≥ 30% in 9 (64%). PSMA PET standardized uptake value (SUV) at screening was predictive of ≥ 30% PSA reduction: SUV max value 17 ± 9 versus 44 ± 15 (P < .007), and PSMA SUV mean 6 ± 4 versus 10 ± 4 (P < .04). FDG parameters alone, and volume or site of disease did not predict PSA response. No imaging parameters predicted ≥ 50% PSA reduction. Nine of 14 men were reimaged after treatment, revealing 3 distinct patterns of progression.. PSMA PET plays an important role in predicting treatment response to Lu-PSMA and in identifying subsequent patterns of failure, which may aid in determining the next best treatment options.

Topics: Aged; Aged, 80 and over; Dipeptides; Disease Progression; Follow-Up Studies; Heterocyclic Compounds, 1-Ring; Humans; Image Processing, Computer-Assisted; Lutetium; Male; Middle Aged; Pilot Projects; Positron-Emission Tomography; Prognosis; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radioisotopes; Survival Rate

Topics: Administration, Oral; Aged; Aged, 80 and over; Bone Marrow; Dipeptides; Glutamic Acid; Half-Life; Heterocyclic Compounds, 1-Ring; Humans; Infusions, Intravenous; Kidney; Lutetium; Male; Mannitol; Middle Aged; Parotid Gland; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radiation Dosage; Radioisotopes; Radiopharmaceuticals; Tablets

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

Prostate-specific membrane antigen (PSMA) is an excellent target for radionuclide therapy of metastasized castration-resistant prostate cancer (mCRPC). Besides high affinity and long tumor retention, the DOTA-conjugated ligand PSMA-617 has low kidney uptake, making it an excellent choice for therapeutic application. We retrospectively report our experience with (177)Lu-PSMA-617-targeted radionuclide therapy in a case series of mCRPC patients resistant to other treatments.. Patients with PSMA-positive tumor phenotypes were selected by molecular imaging. Thirty patients received 1-3 cycles of (177)Lu-PSMA-617. During therapy, pharmacokinetics and radiation dosimetry were evaluated. Blood cell count was checked every 2 wk after the first and every 4 wk after succeeding cycles. Prostate-specific antigen (PSA) was determined every 4 wk. Radiologic restaging was performed after 3 cycles.. Twenty-one of 30 patients had a PSA response; in 13 of 30 the PSA decreased more than 50%. After 3 cycles, 8 of 11 patients achieved a sustained PSA response (>50%) for over 24 wk, which also correlated with radiologic response (decreased lesion number and size). Normally, acute hematotoxicity was mild. Diffuse bone marrow involvement was a risk factor for higher grade myelosuppression but could be identified by PSMA imaging in advance. Xerostomia, nausea, and fatigue occurred sporadically (<10%). Clearance of non-tumor-bound tracer was predominantly renal and widely completed by 48 h. Safety dosimetry revealed kidney doses of approximately 0.75 Gy/GBq, red marrow doses of 0.03 Gy/GBq, and salivary gland doses of 1.4 Gy/GBq, irrespective of tumor burden and consistent on subsequent cycles. Mean tumor-absorbed dose ranged from 6 to 22 Gy/GBq during cycle 1.. (177)Lu-PSMA-617 is a promising new option for therapy of mCRPC and deserves more attention in larger prospective trials.

Topics: Aged; Aged, 80 and over; Antigens, Surface; Biomarkers, Tumor; Dipeptides; Glutamate Carboxypeptidase II; Heterocyclic Compounds, 1-Ring; Humans; Lymphatic Metastasis; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radiopharmaceuticals; Treatment Outcome

Lu-PSMA was approved in the USA for patients with prostate-specific membrane antigen-positive metastatic castration-resistant prostate cancer already treated with androgen receptor pathway inhibition and taxane-based chemotherapy on the basis of results from VISION. Three limitations affected the control arm in VISION: choice of the standard of care was limited, some patients initially deemed ineligible for taxane later received it, and there was a high attrition rate. VISION is an example of the many challenges in modern oncology trials. The direct and indirect costs of Lu-PSMA also mean that this therapy is likely to be out of reach for many nations, deepening global inequities in health care access.

Topics: Humans; Lutetium; Male; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radioisotopes; Taxoids; Treatment Outcome

Topics: Dipeptides; Humans; Lutetium; Male; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant

Topics: Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Longitudinal Studies; Lutetium; Male; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; United States

The currently used scheme for radioligand therapy (RLT) of patients with metastatic castration-resistant prostate cancer (mCRPC) consists of 4-6 cycles of 6.0-7.4 GBq [. Further PSA decline of 33 ± 28% during the extended treatment was observed in 21/26 (81%) patients, whereas 5/26 (19%) patients showed a PSA increase; correspondingly in 11/21 patients with an initial response (PR or SD) to extended cycles, treatment was discontinued due to progressive disease, whereas six (23%) patients achieved low-volume residual disease. Two (8%) patients died without showing progression, and two (8%) patients are still under therapy. The median progression-free survival was 19 (95% CI: 15-23) months, and the overall survival was 29 (95% CI: 18-40) months. Grade ≥ 3 hematological toxicities occurred in 4/26 (15%) patients during treatment extension, and nephrotoxicity (grade ≥ 3) was observed in 1/26 (4%) patient during the follow-up.. Extended radioligand therapy is a feasible treatment option in patients with high-volume residual tumor after the completion of standard treatment with six cycles of [

Topics: Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Lutetium; Male; Neoplasm, Residual; Positron Emission Tomography Computed Tomography; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Retrospective Studies; Treatment Outcome

Androgen deprivation therapy plays an integral role in the treatment algorithm of advanced prostate cancer. Enzalutamide has shown great benefit in castrate-sensitive as well as resistant prostate cancer. Few studies have shown that enzalutamide can potentially increase the PSMA expression on 68 Ga-PSMA-11 PET/CT imaging in patients with metastatic castrate-resistant prostate cancer. We present an interesting case where addition of short course of enzalutamide resulted in increased localization of 177 Lu-PSMA-617 in metastatic lesions on posttherapy scan pointing to the added benefit of PSMA RLT.

Topics: Androgen Antagonists; Heterocyclic Compounds, 1-Ring; Humans; Lutetium; Male; Positron Emission Tomography Computed Tomography; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Treatment Outcome

An 85-year-old man with advanced metastatic castration-resistant prostate cancer and progression after 8 cycles of 177 Lu-prostate-specific membrane antigen (PSMA)-617 radioligand therapy (RLT) received 1 cycle of 161 Tb-PSMA RLT. This one administration of 6.5 GBq 161 Tb-PSMA-617 resulted in impressive partial remission with a PSA decline by 53.4% (from 474 to 221 ng/mL) and a concomitant decrease in tumor burden on PSMA PET/CT imaging. The presented case provides stunning initial evidence of the therapeutic potential of 161 Tb-PSMA RLT in metastatic castration-resistant prostate cancer, even in patients progressing after extensive 177 Lu-based RLT. 161 Tb-labeled PSMA ligands may thus offer a promising alternative to standard PSMA RLT.

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

The aim of this study was to systematically evaluate the effect of thresholding algorithms used in computer vision for the quantification of prostate-specific membrane antigen positron emission tomography (PET) derived tumor volume (PSMA-TV) in patients with advanced prostate cancer. The results were validated with respect to the prognostication of overall survival in patients with advanced-stage prostate cancer.. A total of 78 patients who underwent [. The whole-body PSMA-TVs, quantified using different thresholding methods, demonstrate a high positive correlation with the baseline methods. We observed the highest correlation with generalized histogram thresholding (GHT) (Pearson r (r), p value (p): r = 0.977, p < 0.001) and Sauvola thresholding (r = 0.974, p < 0.001) and the lowest correlation with Multiotsu (r = 0.877, p < 0.001) and Yen thresholding methods (r = 0.878, p < 0.001). The median survival time of all patients was 9.87 months (95% CI [9.3 to 10.13]). Stratification by median whole-body PSMA-TV resulted in a median survival time from 11.8 to 13.5 months for the patient group with lower tumor burden and 6.5 to 6.6 months for the patient group with higher tumor burden. The patient group with lower tumor burden had significantly higher probability of survival (p < 0.00625) in eight out of nine thresholding methods (Fig. 2); those methods were SUVmax50 (p = 0.0038), SUV ≥3 (p = 0.0034), Multiotsu (p = 0.0015), Yen (p = 0.0015), Niblack (p = 0.001), Sauvola (p = 0.0001), Otsu (p = 0.0053), and Li thresholding (p = 0.0053).. Thresholding methods commonly used in computer vision are promising tools for the semiautomatic quantification of whole-body PSMA-TV in [

Topics: Gallium Radioisotopes; Humans; Male; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Prostate-Specific Antigen; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; Retrospective Studies; Tumor Burden

Metastatic castration-resistant prostate cancer (mCRPC) is characterized by heterogeneity among patients as well as therapy responses due to diverse genetic, epigenetic differences, and resistance mechanisms. At this stage of the disease, therapy modalities should be individualized in light of the patients' clinical state, symptoms, and genetic characteristics. In this prospective study, we aimed to evaluate the outcome of patients with mCRPC treated with. Median OS and PSA-PFS were 17.7 (95% confidence interval [CI]: 15.2-20.2) and 6.6 months (95% CI: 4.5-8.8), respectively. Primary resistance to PSMA-RLT (hazard ratio [HR]: 12.57, 95% CI: 2.4-65.2, p: 0.003), <30% PSA response rate after first cycle of PSMA-RLT (HR: 1.016, 95% CI: 1.006-1.03, p: 0.003), FDG > PSMA disease (HR: 4.9, 95% CI: 1.19-20.62, p: 0.03), PSA doubling time (PSA DT) of ≤2.4 months (HR: 15.7, 95% CI: 3.7-66.4, p: <0.0001), and low hemoglobin levels (HR: 0.59, 95% CI: 0.41-0.83, p: 0.003) were correlated with poor OS in the multivariate analysis. Bone scintigraphy >  PSMA disease (HR: 5.6; 95% CI: 1.8-17, p: 0.002) and high C-reactive protein (HR: 1.4, 95% CI: 1.1-1.7, p: 0.001) were significant predictive biomarkers for PFS in the multivariate analysis.. PSA response rate and pattern to PSMA-RLT are the most important predictors of survival in patients receiving PSMA-RLT. Being a strong predictive biomarker, combined FDG and PSMA PET can be helpful for the decision of PSMA-RLT eligibility.

Topics: Fluorodeoxyglucose F18; Humans; Male; Positron Emission Tomography Computed Tomography; Prognosis; Progression-Free Survival; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Retrospective Studies; Treatment Outcome

Topics: Dipeptides; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant

This project focuses on the generation and evaluation of functional alternatives to radiometal-based pharmaceuticals supporting basic research and the in vitro developmental phase. Employing robust tritium chemistry and non-radioactive metal surrogates in two synthetic and labeling strategies resulted in ([ring-

Topics: Dipeptides; Glutamate Carboxypeptidase II; Heterocyclic Compounds, 1-Ring; Humans; Lutetium; Male; Pharmaceutical Preparations; Prostatic Neoplasms, Castration-Resistant; Radiopharmaceuticals; Tritium

Topics: Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Lutetium; Male; Patient Selection; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radioisotopes

Topics: Humans; Lutetium; Male; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radioisotopes; Radiopharmaceuticals; Treatment Outcome

For the implementation of suitable radiation safety measures in [. Both the short-term (up to 24 h, n = 28 cycles) and long-term kinetics (up to 7 weeks, n = 35 samples) were evaluated by collection of urine samples. Samples were measured on a scintillation counter to determine excretion kinetics.. The mean excretion half-time during the first 20 h was 4.9 h. Kinetics was significantly different for patients with kidney function below or above eGFR 65 ml/min. Calculated skin equivalent dose in case of urinary contamination was between 50 and 145 mSv when it was caused between 0 and 8 h p.i.. Measurable amounts of. Excretion kinetics of [

Topics: Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Lutetium; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; Radiopharmaceuticals

Despite the existence of various treatment options, the prognosis for patients with metastatic castration-resistant prostate cancer (mCRPC) remains unfavorable. One potential therapeutic approach is the use of [. [

Topics: Aged; Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Lutetium; Male; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Treatment Outcome

Topics: Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Taxoids

177 Lu-PSMA radioligand therapy (RLT) has shown very encouraging results in metastatic castrate-resistant prostate cancer (mCRPC) patients with acceptable adverse events. The adverse events of RLT are mainly limited to salivary glands and kidneys. However, there is dearth of available data of RLT in transplanted kidney patients with mCRPC. Here is a case of 68-year-old mCRPC patient with history of renal transplant who underwent 4 cycles of 177 Lu-PSMA-617 RLT (~7.4 GBq/cycle). Posttherapy serum creatinine and glomerular filtration rate remained stable along with excellent response and symptomatic improvement, thus demonstrating the safety of full dose of 177 Lu-PSMA in renal transplant patients.

Topics: Aged; Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Kidney; Lutetium; Male; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radiopharmaceuticals; Retrospective Studies; Treatment Outcome

177 Lu-prostate-specific membrane antigen (PSMA) for metastatic castration-resistant prostate cancer has emerged as a very promising therapy. However, some of the PSMA-expressing positive metastatic castration-resistant prostate cancer patients never respond or develop resistance to 177 Lu-PSMA. We present a case of castration-resistant prostate cancer with multiple bone metastases. Remission of clinical symptoms and imaging lesions can be observed after 4 cycles of 225 Ac-PSMA-617 therapy. Moreover, the man did not have any observable adverse effects.

Topics: Bone Neoplasms; Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Lutetium; Male; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radiopharmaceuticals; Treatment Outcome

Preliminary data from retrospective analyses and recent data from large randomized controlled trials suggest safety and efficacy of radioligand therapy (RLT) targeting prostate-specific membrane antigen (PSMA) in men with metastatic castration-resistant prostate cancer (mCRPC). Limited data on this modality have been published regarding large samples treated in everyday practice.. In a large, prospectively observed "real-world" cohort with late-stage/end-stage mCRPC and conventional treatment failure,

Topics: Aged; Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Lutetium; Male; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radioisotopes; Registries; Retrospective Studies; Treatment Outcome

To examine the clinical benefit of Lu-177-PSMA-617 radioligand therapy for patients with metastatic castration-resistant prostate cancer (mCRPC).. Between November 2014 and December 2018, a total of 56 consecutive patients (median age 69.5 years; range 55-84 years) with mCRPC were included in this retrospective analysis. Patients received between 1 and 4 therapy cycles with a mean activity of 6.8 GBq per cycle. Biochemical response was evaluated using Prostate Cancer Working Group Criteria 3 (PCWG 3). Survival was assessed using Kaplan-Meier estimates and Cox proportional hazards regression analysis. This retrospective study was approved by the local ethics committee.. A total of 139 treatment cycles with Lu-177-PSMA-617 were performed. A decline of 50% or more of prostate-specific antigen (PSA) level occurred in 54% and a PSA decline of any amount in 65% of patients. The estimated median overall survival (OS) was 16 months, in the chemotherapy subgroup 14 months. A longer OS was associated with a PSA-decline ≥50%, more than 2 cycles of therapy, cumulative activity >15 GBq and an initial alkaline phosphatase ≤ 220 [U/l]. These identified predictors remained significant on uni- and multivariate Cox regression analysis. Moreover, 40% of the patients who were non-responders after the first therapy cycle turned into responders after the second one.. PSA-decline ≥50%, a cumulative activity >15 GBq and an initial alkaline phosphatase ≤ 220 [U/l] were identified as key predictors of prolonged OS in patients with mCRPC. In contrast rapid clinical deterioration mostly due to skeletal carcinomatosis resulted in early treatment failure.. ZIEL: Es sollte der klinische Nutzen der Lu-177-PSMA-617-Radioligandentherapie bei Patienten mit metastasiertem kastrationsresistentem Prostatakrebs (mCRPC) untersucht werden.. In diese retrospektive Analyse zwischen November 2014 und Dezember 2018 wurden insgesamt 56 konsekutive Patienten (medianes Alter 69,5 Jahre; Bereich 55–84 Jahre) mit mCRPC eingeschlossen. Die Patienten erhielten zwischen 1 und 4 Therapiezyklen mit einer mittleren Aktivität von 6,8 GBq pro Zyklus. Das biochemische Ansprechen wurde anhand der Kriterien der „Prostate Cancer Working Group“ (PCWG 3) bewertet. Das Überleben wurde mittels Kaplan-Meier-Schätzer und einer proportionalen Cox-Hazard-Regressionsanalyse bewertet. Diese retrospektive Studie wurde von der zuständigen Ethikkommission genehmigt.. Insgesamt wurden 139 Behandlungszyklen mit Lu-177-PSMA-617 durchgeführt. Eine Abnahme des Prostata-spezifischen Antigens (PSA) um 50 % oder mehr trat bei 54 % und eine PSA-Abnahme in beliebiger Höhe bei 65 % der Patienten auf. Das geschätzte mediane Gesamtüberleben (OS) betrug 16 Monate, in der Chemotherapie-Untergruppe 14 Monate. Ein längeres OS war verbunden mit einem PSA-Abfall ≥50%, mehr als 2 Therapiezyklen, einer kumulativen Aktivität >15 GBq und einem initialen Wert für alkalischen Phosphatase ≤220 [U/l]. Diese identifizierten Prädiktoren blieben in der uni- und multivariaten Cox-Regressionsanalyse signifikant. Außerdem wurden 40 % der Patienten, die nach dem ersten Therapiezyklus nicht auf die Therapie ansprachen (Non-Responder), nach dem zweiten Zyklus zu Respondern.. Ein PSA-Abfall von ≥50%, eine kumulative Aktivität von >15 GBq und ein initialer Wert für alkalische Phosphatase von ≤220 [U/l] wurden als Schlüsselprädiktoren für ein längeres OS bei Patienten mit mCRPC identifiziert. Im Gegensatz dazu führte eine rasche klinische Verschlechterung, meist aufgrund einer Skelettkarzinose, zu einem frühen Therapieversagen.

Topics: Aged; Aged, 80 and over; Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Lutetium; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radioisotopes; Retrospective Studies; Treatment Outcome

In the last decade, many life-prolonging therapeutic options have emerged for metastatic castration-resistant prostate cancer (mCRPC). The recent VISION trial is the first to demonstrate a survival benefit of Lutetium-177[

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

177Lu-PSMA-617 radioligand therapy (RLT) has evolved as a suitable alternative to existing therapeutic options in patients with metastatic castration-resistant prostate cancer. With the emergence of α-emitters such as 225Ac, the efficacy of PSMA-RLT has further improved. Xerostomia and myelosuppression are common early treatment-emergent adverse events in patients receiving this therapy; however, data on long-term toxicity are relatively scarce. In this report, we describe a 76-year-old man with metastatic castration-resistant prostate cancer, who after having an initial excellent response to 2 cycles of 225Ac-PSMA-617 RLT, developed delayed nephrotoxicity in the form of tubulointerstitial nephritis.

Topics: Actinium; Aged; Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Lutetium; Male; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Treatment Outcome

The phase III VISION trial using

Topics: Clinical Trials, Phase III as Topic; Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Lutetium; Male; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; United States

Systemic Lutetium-177 prostate-specific membrane antigen-617 radioligand therapy (Lu-177-PSMA-617-RLT) is a novel treatment approach in patients suffering from metastasized castration-resistant prostate cancer. Nonetheless, a therapeutic response may fail to appear in a proportion of patients. This study aims to identify routinely obtainable pre- and intratherapeutic parameters to allow a prediction of overall survival in patients receiving Lu-177-PSMA-617 radioligand therapy.. Between January 2015 and December 2020 52 patients treated with a total of 146 cycles Lu-177-PSMA-617-RLT were retrospectively analysed in a single-center trial. The median overall survival time (OS) was compared to pre-therapeutic serological parameters, the extend of metastatic spread and previously performed therapies using Kaplan-Meier estimators and multivariate Cox-regression. Bonferroni-Holm correction was performed on all statistical tests.. The median OS of all patients was 55.6 weeks. Multivariate Cox-regression revealed significant lower survival for decreased pretherapeutic hemoglobin levels (HR 0.698 per g/dl; 95%-CI 0.560-0.872; p = 0.001), increased lactate dehydrogenase (LDH) levels (HR 1.073 per 25 U/l; 95%-CI 1.024-1.125; p = 0.003) and the presence of hepatic metastasis (HR 6.981; 95%-CI 2.583-18.863; p < 0.001). Increased pretherapeutic c-reactive protein (CRP), alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT) levels were also associated with a shorter survival. A prostate-specific antigen decline after one therapy cycle did not significantly correlate with an increased survival. No significant relations were observed between overall survival time and other serological parameters or previously performed therapies.. Pre-therapeutic hemoglobin and LDH levels, as well as the presence of hepatic metastasis are independent predictors of overall survival in patients receiving Lu-177-PSMA-617-RLT. CRP, ALP and GGT levels cloud be utilized as additional decision aids when a Lu-177-PSMA-617-RLT is intended. Trial Registration Not applicable (retrospective observational study).

Topics: Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Liver Neoplasms; Lutetium; Male; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radioisotopes; Retrospective Studies

Topics: Heterocyclic Compounds, 1-Ring; Humans; Lutetium; Male; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant

Topics: Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radiopharmaceuticals

[. We retrospectively analyzed clinical, renal, and salivary scintigraphy data and salivary [. In total, 54 PSMA PET scans, 98 kidney, and 98 salivary scintigraphy results were evaluated. There were no significant differences for the ejection fraction, peak time, and residual activity after 5 min for both parotid and submandibular glands prior to each cycle and 4 weeks after the last cycle. Similarly, no significant differences in serum creatinine and renal scintigraphy parameters were observed prior to each cycle and 4 weeks after the last treatment. Despite there being no changes in the metabolic volume of both submandibular glands, SUVmax values dropped significantly (. Results evidenced no alterations in renal function and only minimal impairment of salivary function of mCRPC patients who acquired an intense PSMA-RLT regimen every 4 weeks.

Topics: Aged; Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Kidney; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radiopharmaceuticals; Retrospective Studies; Salivary Glands

Lutetium labelled prostate-specific membrane antigen radioligand therapy (Lu-PSMA RLT) has shown pleasing early results in management of high-volume metastatic castration resistant prostate cancer (mCRPC), but its role in the early treatment of men with only lymph node metastasis (LNM) is unknown. The aim was to assess the outcome of Lu-PSMA RLT earlier in the treatment of men with only LNM.. Single institution retrospective review of men with only LNM on staging Ga-PSMA PET PSMA who proceeded with Lu-PSMA RLT.. There were 17 men with only LNM, including 13 with mCRPC and 3 who were both hormone and chemotherapy naïve. The median PSA was 3.7 (0.46-120 ng/mL). A PSA decline of ≥50% occurred in 10/17 (58.8%), decreasing to <0.2 ng/mL in 35.3% (6/17). The PSA continues to decline or remain stable in 10/17 (58.8%) with a median follow-up of 13 months, and 8/17 (47.1%) have not reached their pre-treatment levels. There were no significant side effects. There was a better PSA response in men without prior chemotherapy (p=0.05). The prostate cancer specific and overall survival is 82.4% (14/17).. Our results identify improved PSA response to Lu-PSMA RLT in men with only LNM, especially in the chemotherapy naïve cohort, compared to previous series with more advanced mCRPC. These findings provide important proof of principle to aid with planning of future prospective randomized trials evaluating the role of Lu-PSMA RLT earlier in the management of node metastatic prostate cancer, including men naïve of ADT and chemotherapy.

Topics: Antigens, Surface; Antineoplastic Agents; Dipeptides; Glutamate Carboxypeptidase II; Heterocyclic Compounds, 1-Ring; Humans; Ligands; Lutetium; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radiopharmaceuticals; Survival Analysis; Time-to-Treatment; Treatment Outcome; Tumor Burden

We investigated whether periodontal disease is associated with specific stroke subtype.. This is a single-center cross-sectional study. Periodontal disease was assessed in stroke and transient ischemic attack patients. Strokes caused by large-artery atherosclerosis were classified as intracranial atherosclerosis or extracranial atherosclerosis as well as anterior or posterior circulation disease.. We report a higher proportion of stroke due to large-artery atherosclerosis in patients with periodontal disease compared to those without periodontal disease. We report an independent association between periodontal disease and intracranial atherosclerosis, as well as between periodontal disease and posterior circulation disease.

Topics: Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Lutetium; Male; Matched-Pair Analysis; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Treatment Outcome; Urea

The impact of prior therapies, especially chemotherapy, on overall survival (OS) in patients with castration-resistant prostate cancer (CRPC) receiving [. The data of 631 metastatic CRPC (mCRPC) patients from 11 different clinics were evaluated. According to the inclusion and exclusion criteria, all patients had to have received at least abiraterone or enzalutamide prior to [. The analysis included the data of 416 patients, with a median age of 71.9 years. At the time of analysis, 87 patients (20,9%) were still alive. A total of 53.6% of patients had received both abiraterone and enzalutamide; 75.5% and 26.4% had a history of chemotherapy with docetaxel and cabazitaxel, respectively. A total of 20.4% had had Ra-223. The median OS was 11.1 months. Prior chemotherapy, the existence of bone and liver metastases, as well as Eastern Cooperative Oncology Group (ECOG) status, were significant prognosticators of worse overall survival in both univariate and multivariate analyses. Patients without any prior chemotherapy showed a significantly longer OS (14.6 months). The median OS in patients who received one or two lines of chemotherapy with docetaxel or docetaxel followed by cabazitaxel, respectively, was 10.9 months and 8.9 months. There was no difference in OS between patients who had not received chemotherapy and patients for whom chemotherapy was contraindicated. The other prior therapies did not have any significant impact on OS.. In the present multicenter analysis, chemotherapy-naïve mCRPC patients receiving [

Topics: Aged; Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Male; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radiopharmaceuticals; Radium; Retrospective Studies; Treatment Outcome

[. Data of 61 patients (mean age 71.6 ± 6.9 years, median basal PSA 70.7 [range 1.0-4890 μg/L]), pretreated with abiraterone/enzalutamide (75.4%) and docetaxel/cabazitaxel (68.9%), received three cycles of PSMA-RLT (mean 7321 ± 592 MBq) at four weekly intervals and were analyzed retrospectively. General medical conditions and laboratory parameters of every patients were regularly assessed. Response to therapy was based on PSA levels 1 month after the 3rd cycle. Binary logistic regression test and Kaplan-Meier estimates were used to evaluate predictors and overall survival (OS).. Forty-nine (80.3%) patients demonstrated a therapy response in terms of any PSA decline, while 21 (19.7%) patients showed increase or no changes in their PSA levels. Baseline hemoglobin (Hb) significantly predicted PSA reductions of ≥ 50% 4 weeks after receiving the 3rd PSMA-RLT (P = 0.01, 95% CI: 1.09-2.09) with an AUC of 0.68 (95% CI: 0.54-0.81). The levels of basal Hb and basal PSA were able to predict survival of patients, both P < 0.05 (relative risk 1.51 and 0.79, 95% CI: 1.09-2.09 and 0.43-1.46), respectively. In comparison to patients with reduced basal Hb, patients with normal basal Hb levels lived significantly longer (median survival not reached vs. 89 weeks, P = 0.016). Also, patients with basal PSA levels ≤ 650 μg/L had a significantly longer survival than patients with basal PSA levels > 650 μg/L (median survival not reached vs. 97 weeks, P = 0.031). Neither pretreatments with abiraterone/enzalutamide or docetaxel/cabazitaxel nor distribution of metastasis affected survival and rate of response to PSMA-RLT.. Basal Hb level is an independent predictor for therapy response and survival in patients receiving PSMA-RLT every 4 weeks. Both baseline PSA ≤ 650 μg/L and normal Hb levels were associated with longer survival.

Topics: Aged; Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Lutetium; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radiopharmaceuticals; Retrospective Studies; Treatment Outcome

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

Topics: Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Taxoids

Prostate-specific membrane antigen (PSMA)-based radioligand therapy (RLT) showed in a multicentre WARMTH (World Association of Radiopharmaceutical and Molecular Therapy) study that the presence of bone metastases is a negative prognosticator for the survival. The current multicentre retrospective analysis aims to evaluate the response rate to RLT, the overall survival (OS) of patients and the safety of the treatment according to the extent of bone involvement.. The study included patients with progressive metastatic castration-resistant prostate cancer (mCRPC), who underwent RLT with [. A total of 319 males were included in the analysis. The extent of bone metastases and PSA response did not correlate significantly. Any PSA decline was observed in 73% patients; 44% showed a decline of ≥50%. The median OS of patient in the different subgroups was 18 months (less than 6 lesions), 13 months (6-20 lesions), 11 months (more than 20 lesions) and 8 months (diffuse involvement), respectively (p < 0.0001). Patients with prior Ra-223-therapy showed longer OS in all subgroups, especially in the subgroups with 6-20 lesions (OS: 16 vs. 12 months; p = 0.038) as well as diffuse involvement (OS: 11 vs. 7 months; p = 0.034). Significant negative prognosticators of OS were the existence of liver metastases in all subgroups and prior chemotherapy in patients with <6 bone lesions. Anaemia and thrombocytopenia correlated positively with the extent of bone metastases: p < 0.0001 and 0.005, respectively. No patient showed a high grade leukopenia.. The extent of bone involvement correlated negatively with the OS after RLT; however, it showed no relevant correlation with the PSA response rate. Prior therapy with Ra-223 may have a positive impact on OS. Haematotoxicity was higher in patients with more than 20 bone lesions; nevertheless, the majority of these patients did not show a relevant haematotoxicity.

Topics: Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radium; Retrospective Studies; Treatment Outcome

The purpose of this analysis was to report the safety evaluation of

Topics: Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radiometry

Topics: Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Lutetium; Male; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radioisotopes

[. Fifty-four patients (mean age 72 ± 7 years, median PSA at time of initial therapy 66 [range 1.0-4890 μg/L]), receiving three PSMA-RLT cycles (mean 7315 ± 573 MBq) at four weekly intervals, were included in this retrospective analysis. Hematological and biochemical parameters were regularly determined in every patient. Kaplan-Meier estimates were used to assess PFS and OS and a Cox proportional hazard model was used to analyze significant associations. Treatment response was based on PSA measurements 4 weeks after the 3rd treatment.. The majority of patients were previously treated with abiraterone/enzalutamide (69%) and docetaxel/cabazitaxel (67%). In total, 79% of the patients showed a decrease in PSA (median PSA decrease from 66 to 19.8, range 0.7-4563 μg/L, P < 0.001) 1 month after the 3rd therapy cycle. Among them, 58% and 35% demonstrated a PSA-decline of > 50% and > 80%, respectively. Median OS was 119 weeks; median PFS was 25 weeks. Patients presenting with a PSA decline had significantly longer PFS (27 vs. 15 weeks, P < 0.0001) and OS (median survival not reached vs. 52 weeks, P < 0.001) than patients with no PSA reduction. Moreover, patients with reduction in PSA levels ≥ 50% (median survival not reached vs. 52 weeks, P < 0.0001) and ≥ 80% (median survival not reached vs. 87 weeks, P = 0.008) lived significantly longer. While hemoglobin did not change during treatment, levels of platelets (236 ± 71 g/L vs. 193 ± 67 g/L) and leucocytes (6.5, range 2.9-13.7 g/L vs. 4.8, range 1.5-12.3 g/L) decreased significantly, both P < 0.001. Two grade 3 leukocytopenia and one grade 3 anemia were observed.. Intense PSMA-RLT regime with four weekly intervals between the cycles is well-tolerated and offers favorable response rates, PFS, and survival rates for patients with mCRPC.

Topics: Aged; Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Retrospective Studies; Treatment Outcome

Radioligand therapy with [. A total number of 78 consecutive patients with mCRPC and a history of first-line chemotherapy were included in this retrospective analysis. The outcome of patients treated with 6.0 GBq [. There was no significant difference comparing the rate of > 50% PSA decline or best PSA response between the 6.0 GBq and 7.5 GBq group (35% vs. 54%, p = 0.065; and - 40.2% vs. - 57.8%, p = 0.329). The median estimated survival and PSA-PFS did not significantly differ between the 6.0 GBq and 7.5 GBq groups as well (11.3 vs. 12.7 months, p = 0.384; and 9.5 vs. 12.3 months, p = 0.258). There was no significant difference regarding the change of kidney, liver, and blood cell parameters under therapy between the treatment groups.. Higher cumulated doses of [

Topics: Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Male; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Retrospective Studies; Treatment Outcome

We analysed quantitative biomarkers derived from both baseline whole-body imaging and blood serum to identify prognostic markers in patients treated within the lutetium-177 prostate-specific membrane antigen (LuPSMA) phase 2 trial.. PET image analysis was carried out using whole-body segmentation quantifying molecular tumour volume (SUV > 3 threshold for PSMA, SUV > liver+2sd for fluorodeoxyglucose (FDG) including SUVmax and SUVmean. For baseline bone scans, EXINI bone scan index (BSI) was used to calculate the percentage of involved bone. Baseline alkaline phosphatase (ALP), lactate dehydrogenase (LDH), prostate specific antigen (PSA) and PSA doubling time were also used in this analysis. We used univariate cox regression analysis and log-rank comparison with optimised cut-offs to find suitable biomarkers prognostic of overall survival from time of enrolment.. This analysis identified FDG-positive tumour volume (FDGvol; HR 2.6; 95% CI, 1.4-4.8), mean intensity of PSMA-avid tumour uptake (PSMAmean; HR 0.89; 95% CI, 0.8-0.98), bone scan index (BSI; HR 2.3; 95% CI, 1.2-4.4), ALP (HR 1.1; 95% CI, 1-1.2) and LDH (HR 1.2; 95% CI, 1-1.5) as biomarkers prognostic of overall survival.. In addition to established biomarkers, both FDG and PSMA PET/CT parameters have prognostic significance for survival in men undergoing LuPSMA therapy.

Topics: Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Lutetium; Male; Positron Emission Tomography Computed Tomography; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radioisotopes; Radiopharmaceuticals; Tomography, X-Ray Computed; Treatment Outcome

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

To evaluate the therapeutic response, progression free survival (PFS), overall survival (OS) and clinical toxicity of. A total of 40 mCRPC patients (age range: 46-84 years; median 63 years), who had undergone. The present work explored in a large teriary cancer care setting, the efficacy of

Topics: Aged; Aged, 80 and over; Antigens, Surface; Dipeptides; Fluorodeoxyglucose F18; Gallium Radioisotopes; Glutamate Carboxypeptidase II; Heterocyclic Compounds, 1-Ring; Humans; Lutetium; Male; Middle Aged; Molecular Targeted Therapy; Neoplasm Grading; Positron Emission Tomography Computed Tomography; Prognosis; Progression-Free Survival; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Quality of Life; Radioisotopes; Radiopharmaceuticals; Retrospective Studies; Treatment Outcome

The main side effect of prostate-specific membrane antigen targeting alpha therapy (PSMA TAT) is dry mouth syndrome. Inflammation of the salivary glands and consequent reduced salivary function have been reported in patients after radioiodine therapy. The beneficial effects of sialendoscopy on radiation-induced inflammation in tissue are well known. Thus sialendoscopy with dilatation, saline irrigation and steroid injections (prednisolone) was performed before and after. Eleven men with metastatic castration-resistant prostate cancer (mean age 68.5 years, range 58-80 years) underwent sialendoscopy, dilatation, saline irrigation and steroid injection of both submandibular and both parotid glands before or after every cycle of. In all 11 patients both parotid and both submandibular glands were affected by radiation sialadenitis and sialendoscopy was performed. The patients experienced no complications after sialendoscopy, and showed a significant improvement in HRQOL as measured using the XQ and XI. After sialendoscopy the XQ score decreased significantly from 77.7 ± 13.6 to 42.7 ± 14.8 (p = 0.003) and the XI score decreased from 44.5 ± 6.9 to 25.8 ± 12.8 (p = 0.003). Due to the limited number of patients we only report tendencies.. Sialendoscopy with dilatation, saline irrigation and steroid injection had beneficial effects on salivary gland function and HRQOL in patients undergoing

Topics: Actinium; Aged; Aged, 80 and over; Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Male; Middle Aged; Prednisolone; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radiopharmaceuticals; Salivary Glands; Surgery, Computer-Assisted; Therapeutic Irrigation; Xerostomia

Topics: Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radioisotopes

Ac-based PSMA-targeted therapy has emerged as promising agent for the treatment of metastatic castration-resistant prostate cancer. Posttherapy image is used for tracer localization and dosimetry. Prior 2 photopeaks of 440 and 218 KeV were reported for posttherapy imaging. Our study of gamma ray spectrum, phantom, and clinical images show that imaging with 3 major photopeaks of 78, 218, and 440 KeV gives better quality images, high count statistics, and higher number of lesion delineations. It is therefore suggested that posttherapy imaging may be carried out using 3 major abundant photopeaks.

Topics: Actinium; Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Male; Middle Aged; Positron-Emission Tomography; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radiometry; Radiopharmaceuticals; Reference Standards

Combined Ga-PSMA-617 PET imaging and Lu-PSMA-617 therapy is a precise targeted theranostic approach for patients with metastatic castration-resistant prostate cancer (mCRPC). The purpose of this study was to determine whether pretherapeutic standard uptake value (SUV) in Ga-PSMA-617 PET could indicate the effective dose in the main organs and absorbed dose in tumor lesions.. After institutional review board approval and informed consent, 9 patients with mCRPC were recruited and underwent Ga-PSMA-617 PET/CT scans. Five patients received Lu-PSMA-617 (1.30-1.42 GBq, 35-38.4 mCi) and then underwent serial whole-body planar imaging and SPECT/CT imaging of both thoracic and abdominal regions at 0.5-, 2-, 24-, 48-, and 72-hour time points. The other 4 patients received Lu-EB-PSMA-617 (0.80-1.1 GBq, 21.5-30 mCi) and then underwent the same imaging procedures at 2-, 24-, 72-, 120-, and 168-hour time points. The effective dose in the main organs and the absorbed dose in tumor lesions were calculated. Detailed correlations between the pretherapeutic SUV in Ga-PSMA-617 PET and effective dose in the main organs as well as absorbed dose in the tumor lesions were analyzed.. SUV of Ga-PSMA-617 PET was moderately correlated with effective dose in main organs (r = 0.610 for Lu-PSMA-617, r = 0.743 for Lu-EB-PSMA-617, both P < 0.001). SUV of tumor lesions in Ga-PSMA-617 PET had high correlation with those in Lu-PSMA-617 (r = 0.915, P < 0.001) and moderate correlation with those in Lu-EB-PSMA-617 (r = 0.611, P = 0.002).. Pretherapeutic Ga-PSMA-617 PET may indicate the dosimetry of Lu-PSMA-617 and Lu-EB-PSMA-617. Both the effective dose in main organs and absorbed dose in tumor lesions correlate with SUV of Ga-PSMA-617 PET. This relationship may help select appropriate candidates for peptide receptor radionuclide therapy. Further investigations of larger cohorts are needed to confirm these initial findings.

Topics: Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Lutetium; Male; Positron Emission Tomography Computed Tomography; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radiometry; Radiopharmaceuticals; Radiotherapy Dosage; Retrospective Studies; Single Photon Emission Computed Tomography Computed Tomography; Whole Body Imaging

[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

Topics: Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radioisotopes

Topics: Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radioisotopes

Topics: Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radioisotopes

Topics: Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radioisotopes

Topics: Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radioisotopes

Up to 30% of patients with castration-resistant prostate cancer (CRPC) do not show any response to the first cycle of radioligand therapy (RLT) with [. CRPC patients were treated with Lu-PSMA, with a median interval of 8 weeks between each cycle. The tumour marker prostate-specific antigen (PSA) was used as the marker for response evaluation.. Fifty-two patients underwent a total of 190 cycles of RLT (3-6 cycles per patient). Of these, 80.8% showed a decline in PSA 2 months after the first cycle, with 44.2% showing a PSA decline of ≥50%. When compared to baseline PSA, 73.1% showed a PSA decline after the third cycle. 50% of patients that did not show any response to the first cycle also did not respond to the second and third cycles. The median OS was 60 weeks in all patients. The median OS was significantly longer for patients that showed any PSA decline after the first cycle compared to patients without PSA decline (68 vs. 33 weeks). There was a significant difference in median OS between responders and non-responders for a change in PSA after the third cycle compared to baseline PSA.. Patients with a positive response to RLT, regardless of the rate of decline, had a significantly longer median OS. Of the patients that did not show any response to the first cycle, 50% responded to the second or third cycles.

Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Ligands; Lutetium; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radioisotopes; Retrospective Studies; Survival Analysis; Treatment Outcome

Topics: Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Lutetium; Male; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Retrospective Studies

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

Prostate cancer is the second most common primary tumor affecting men worldwide. Among them, 10-20% develop castration resistant prostate cancer (CRPC). Ga-PSMA-PET/CT is an important theranostic agent for the evaluation of CRPC to assess the feasibility of treatment with Lu-PSMA-617 which is a novel therapeutic agent. Interestingly, in certain cases, we have observed non-PSMA-avid lesions despite raised sPSA levels. In this regard, we present a case of cocktail therapy applied using Lu-PSMA-617 and Lu-EDTMP therapy in a 38-year-old male CRPC patient with both soft tissue and extensive skeletal metastases.

Topics: Adult; Dipeptides; Edetic Acid; Gallium Isotopes; Gallium Radioisotopes; Heterocyclic Compounds, 1-Ring; Humans; Male; Oligopeptides; Organometallic Compounds; Organophosphorus Compounds; Positron Emission Tomography Computed Tomography; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radiopharmaceuticals

Topics: Dipeptides; Fluorine Radioisotopes; Heterocyclic Compounds, 1-Ring; Humans; Male; Organ Specificity; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radiopharmaceuticals; Theranostic Nanomedicine; Tissue Distribution; Treatment Outcome

Topics: Alpha Particles; Antigens, Surface; Dipeptides; Glutamate Carboxypeptidase II; Heterocyclic Compounds, 1-Ring; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant