scholarly journals Cold Kit for Prostate-Specific Membrane Antigen (PSMA) PET Imaging: Phase 1 Study of 68Ga-Tris(Hydroxypyridinone)-PSMA PET/CT in Patients with Prostate Cancer

2017 ◽  
Vol 59 (4) ◽  
pp. 625-631 ◽  
Author(s):  
Michael S. Hofman ◽  
Peter Eu ◽  
Price Jackson ◽  
Emily Hong ◽  
David Binns ◽  
...  
2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 213-213
Author(s):  
Benedikt Engels ◽  
Ozan Cem Guler ◽  
Cem Onal ◽  
Mark De Ridder

213 Background: Metastases-directed therapy by metastasectomy or radiotherapy (RT) might delay disease progression and postpone systemic treatment in patients with oligometastatic prostate cancer. Here, we evaluated retrospectively the efficacy and toxicity of 68Ga prostate-specific membrane antigen (PSMA) PET-CT guided radiotherapy (RT) in the treatment of oligometastatic prostate cancer. Methods: A total of 23 prostate cancer patients with biochemical relapse, of which 13 castration-sensitive and 10 castration-resistant, were treated with intensity-modulated and image-guided RT (IMRT-IGRT) on ≤ 3 metastases detected by 68Ga PSMA PET-CT. Androgen deprivation therapy was continued in castration-resistant patients. Local control (LC), progression-free survival (PFS) and overall survival (OS) were estimated with the Kaplan-Meier method. Results: A total of 38 metastases were treated. Involved sites were pelvic bone (n = 16), pelvic lymph nodes (n = 11), para-aortic lymph nodes (n = 6), ribs (n = 3) and vertebral body (n = 2). The median PSA prior to RT was 1.06 ng/ml (range 0.10 – 29.0 ng/ml). A median dose of 43.5 Gy (range, 30-64 Gy) was delivered by IMRT-IGRT in 12-27 fractions. At a median follow-up of 7 months (range, 2-17 months), 19 patients (83%) are in remission. Four patients (17%) developed distant recurrence. The actuarial 1-year LC, PFS and OS rates were 100%, 51% (95% CI 8-83%) and 100%. Castration-sensitive patients displayed a statistically significantly superior PFS on univariate analysis as compared to castration-resistant patients (1-year PFS 67% vs 0%, p < 0.01). One patient experienced grade 2 acute gastro-intestinal toxicity. No grade 3 or more toxic events were observed. Conclusions: By providing optimal LC, low toxicity and a promising PFS in castration-sensitive patients, the current retrospective study illustrated that 68Ga PSMA PET-CT guided RT may be an attractive treatment option in patients with oligometastatic prostate cancer. Validation by randomized trials is eagerly awaited.


Author(s):  
Katharina Kessel ◽  
Robert Seifert ◽  
Matthias Weckesser ◽  
Martin Boegemann ◽  
Sebastian Huss ◽  
...  

Abstract Introduction Fibroblast activation protein (FAP) has been recently presented as new imaging target for malignant diseases and offers high contrast to surrounding normal tissue. FAP tracer uptake has been reported in various tumor entities. The aim of this study was to compare FAP and Prostate-specific membrane antigen (PSMA) expression in primary prostate cancer employing histological analyses and PET imaging in two small patient collectives. Methods Two independent small patient collectives were included in this study. For cohort A, data of 5 prostate cancer patients and 3 patients with benign prostate hyperplasia were included. Patients with prostate cancer were initially referred for PSMA PET staging. Radical prostatectomy was performed in all patients and prostate specimen of patients and biopsies of healthy controls were available for further evaluation. Histological workup included HE and immunohistochemistry using PSMA Ab, FAP Ab. Cohort B consists of 6 Patients with diagnosed mCRPC and available PSMA as well as FAP PET. Results Patients with proven prostate cancer infiltration exhibited strong positivity for PSMA in both primary tumors and lymph node metastases while stainings for FAP were found positive in some cases, but not all (2/5). Controls with BPH presented moderate PSMA staining and in one case also with a positive FAP staining (1/3). PET imaging with FAP seemed to result in more precise results in case of low PSMA expression than PSMA-PET. Conclusions While PSMA staining intensity is a valid indicator of prostate cancer in both primary tumor and lymph node metastases, the expression of FAP seems to be heterogeneous but not necessarily linked to cancer-associated fibroblasts. It is also present in inflammation-associated myofibroblasts. Therefore, its ultimate role in prostate cancer diagnosis remains a subject of discussion.


2019 ◽  
Vol 11 ◽  
pp. 175628721881579 ◽  
Author(s):  
Masood Moghul ◽  
Bhaskar Somani ◽  
Tim Lane ◽  
Nikhil Vasdev ◽  
Brian Chaplin ◽  
...  

Background: The aim of this work was to assess the use of prostate-specific membrane antigen (PSMA)-labelled radiotracers in detecting the recurrence of prostate cancer. PSMA is thought to have higher detection rates when utilized in positron emission tomography (PET)/computed tomography (CT) scans, particularly at lower prostate-specific antigen (PSA) levels, compared with choline-based scans. Methods: A systematic review was conducted comparing choline and PSMA PET/CT scans in patients with recurrent prostate cancer following an initial curative attempt. The primary outcomes were overall detection rates, detection rates at low PSA thresholds, difference in detection rates and exclusive detection rates on a per-person analysis. Secondary outcome measures were total number of lesions, exclusive detection by each scan on a per-lesion basis and adverse side effects. Results: Overall detection rates were 79.8% for PSMA and 66.7% for choline. There was a statistically significant difference in detection rates favouring PSMA [OR (M–H, random, 95% confidence interval (CI)) 2.27 (1.06, 4.85), p = 0.04]. Direct comparison was limited to PSA < 2 ng/ml in two studies, with no statistically significant difference in detection rates between the scans [OR (M–H, random, 95% CI) 2.37 (0.61, 9.17) p = 0.21]. The difference in detection on the per-patient analysis was significantly higher in the PSMA scans ( p < 0.00001). All three studies reported higher lymph node, bone metastasis and locoregional recurrence rates in PSMA. Conclusions: PSMA PET/CT has a better performance compared with choline PET/CT in detecting recurrent disease both on per-patient and per-lesion analysis and should be the imaging modality of choice while deciding on salvage and nonsystematic metastasis-directed therapy strategies.


2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 208-208 ◽  
Author(s):  
Fergus Keane ◽  
Yasser Ged ◽  
Megan Greally ◽  
Michael A. Maher ◽  
Kieran O'Malley ◽  
...  

208 Background: It is estimated that within ten years of primary treatment for prostate cancer up to 40% of patients post radical prostatectomy, and up to 50% of patients post radiotherapy will develop disease recurrence. While monitoring of PSA levels is informative of biochemical recurrence, it may precede radiologically detectable recurrence by months to years, and cannot differentiate local/regional recurrence from systemic disease. This represents a management dilemma for treating physicians. The incorporation of PET probes targeting prostate-specific membrane antigen (PSMA) for prostate cancer shows promise for improving the management of patients with prostate cancer, when used alongside existing imaging techniques, like CT, MRI and bone scans. Methods: Retrospective review of all patients referred from our institution for PSMA imaging was carried out. Baseline clinical features were determined and we analyzed impact of PSMA imaging on management outcomes and survival data. Results: 33 patients referred for 68Ga-PSMA-PET imaging were identified. Median age at diagnosis was 65 years (51 -75). The indication for referral in all patients was biochemical recurrence in the absence of radiological evidence of disease by CT imaging and bone scan. Median PSA at time of referral for PSMA scan was 7.3ug/L (1.4ug/L to 87.7ug/L). 100% of patients (n = 33) were upstaged following PSMA imaging, and 30% (n = 10) had more than one site of metastatic disease identified. Most common sites of metastasis were lymph node and bone. Median number of sites of metastatic disease identified by PSMA imaging was one. These results led to a change in management for 96% patients (n = 32). All patients at the time of this review are alive with a median follow up of 13 months, and median progression-free survival of 11 months. Conclusions: PSMA PET-CT directly led to an alteration in the treatment of the majority of patients in this study. This real world data reflects the growing role of PSMA imaging in influencing clinical decisions for prostate cancer patients with biochemical recurrence. Prospective data from randomized studies are awaited to further validate the role of PSMA PET-CT in this patient cohort.


The Prostate ◽  
2019 ◽  
Vol 79 (6) ◽  
pp. 604-613 ◽  
Author(s):  
Daniel P. Petrylak ◽  
Philip Kantoff ◽  
Nicholas J. Vogelzang ◽  
Anthony Mega ◽  
Mark T. Fleming ◽  
...  

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A365-A365
Author(s):  
Tanya Dorff ◽  
Matthew Rettig ◽  
Jean-Pascal Machiels ◽  
Martijn Lolkema ◽  
Karen Autio ◽  
...  

BackgroundProstate-specific membrane antigen (PSMA) is a clinically validated target for metastatic castration-resistant prostate cancer (mCRPC). AMG 160 BiTE® immuno-oncology therapy redirects T cells to cancer cells by binding to PSMA on cancer cells and CD3 on T cells, leading to T-cell activation, tumor-cell killing, and T-cell expansion. As the BiTE mode of action leads to an upregulation of immune checkpoints, combining AMG 160 with a PD-1 inhibitor may lead to sustained T cell–dependent killing of tumor cells. Cytokine release syndrome (CRS) is a first-dose effect induced by BiTE molecule-mediated T-cell activation. An approach to mitigate CRS is prophylaxis with an anti-inflammatory agent.MethodsThe phase 1 study (NCT03792841) has four parts: AMG 160 monotherapy; AMG 160 in combination with pembrolizumab; AMG 160 monotherapy with etanercept prophylaxis; and AMG 160 monotherapy administered in outpatient centers with 24-hour monitoring. Included in the study are men with histologically/cytologically confirmed mCRPC who are refractory to novel androgen receptor signaling inhibitors: abiraterone, enzalutamide, darolutamide, and/or apalutamide and have failed, refused, or are unsuitable for taxanes; and who have ongoing castration with evidence of progressive disease. Patients who received prior PSMA radionuclide therapy are eligible. Patients with CNS metastases, leptomeningeal disease, spinal cord compression, or active autoimmune disease are excluded. Primary objectives are to evaluate safety and tolerability and determine the MTD or RP2D of AMG 160 monotherapy or in combination with pembrolizumab. Secondary objectives are to characterize pharmacokinetics and preliminary antitumor activity. Evaluation of preliminary antitumor activity will be based on RECIST 1.1 with Prostate Cancer Working Group 3 modifications, PSA response, CTC response, progression-free survival (radiographic and PSA), and overall survival. PSMA PET/CT and FDG PET/CT imaging will be used for evaluation of exploratory objectives (figure 1). The study opened in February 2019 and is currently recruiting patients.Abstract 340 Figure 1Study schemaResultsN/AConclusionsN/ATrial RegistrationNCT03792841Ethics ApprovalThe study was approved by all institutional ethics boards.


2021 ◽  
Author(s):  
Dominic Bagguley ◽  
Sean Ong ◽  
James P Buteau ◽  
Sam Koschel ◽  
Nattakorn Dhiantravan ◽  
...  

Prostate-specific membrane antigen (PSMA) PET/CT is a novel imaging technique for the detection and staging of either primary or recurrent prostate cancer. Early studies demonstrated its improved sensitivity and specificity over and in combination with other currently employed imaging techniques, such as multiparametric MRI, bone scan, PET and CT. However, the lack of strength and confidence in these studies has meant incorporation of PSMA PET/CT into clinical guidelines and practice has been limited to date. In response, a number of high-quality prospective studies have recently emerged and reflect exciting results seen in preceding publications. Here we recount some of the key earlier publications, report results from the latest studies and look to the future discussing some of the eagerly awaited ongoing clinical trials.


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