scholarly journals Renal and Salivary Gland Functions after Three Cycles of PSMA-617 Therapy Every Four Weeks in Patients with Metastatic Castration-Resistant Prostate Cancer

2021 ◽  
Vol 28 (5) ◽  
pp. 3692-3704
Author(s):  
Tim Wollenweber ◽  
Lucia Zisser ◽  
Elisabeth Kretschmer-Chott ◽  
Michael Weber ◽  
Bernhard Grubmüller ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Salivary Gland ◽  
Residual Activity ◽  
Peak Time ◽  
Castration Resistant Prostate Cancer ◽  
Submandibular Glands ◽  
Castration Resistant ◽  
Psma Pet ◽  
Salivary Scintigraphy ◽  
Metabolic Volume

Background: [177Lu]Lu-PSMA-617 radioligand therapy (PSMA-RLT) could affect kidney and salivary gland functions in metastatic castration-resistant prostate cancer (mCRPC) patients. Methods: We retrospectively analyzed clinical, renal, and salivary scintigraphy data and salivary [68Ga]Ga-PSMA-11 ligand PET scan measures such as metabolic volume and SUVmax values of 27 mCRPC men (mean age 71 ± 7 years) before and 4 weeks after receiving three cycles of PSMA-RLT every 4 weeks. Twenty-two patients additionally obtained renal and salivary scintigraphy prior to each cycle. A one-way ANOVA, post-hoc Scheffé test and Cochran’s Q test were applied to assess organ toxicity. Results: 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 (p < 0.05). Conclusion: 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.

ENZA-p: A randomized phase II trial using PSMA as a therapeutic agent and prognostic indicator in men with metastatic castration-resistant prostate cancer treated with enzalutamide (ANZUP 1901).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. TPS177-TPS177
Author(s):  
Louise Emmett ◽  
Shalini Subramaniam ◽  
Alison Yan Zhang ◽  
Andrew James Martin ◽  
Sonia Yip ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Fdg Pet ◽  
Predictive Biomarkers ◽  
Receptor Expression ◽  
Receptor Blockade ◽  
Castration Resistant Prostate Cancer ◽  
Concurrent Administration ◽  
Castration Resistant ◽  
Psma Pet

TPS177 Background: 177Lu‐PSMA‐617 (LuPSMA) is a novel radionuclide with promising activity and tolerability in metastatic, castration-resistant prostate cancer (mCRPC). Pre-clinical studies have shown that androgen receptor blockade with enzalutamide upregulates PSMA-receptor expression, and that PSMA-receptor blockade increases treatment response to enzalutamide. We hypothesise that concurrent administration of LuPSMA and enzalutamide will be synergistic in mCRPC. The aims of ENZA-p are to determine the activity and safety of LuPSMA and enzalutamide in men with mCRPC at high-risk of early progression on enzalutamide alone; and to identify potential prognostic and predictive biomarkers from imaging, blood, and tissue. Methods: This open-label, randomised, multicentre, phase 2 trial will recruit 160 men with mCRPC. Key eligibility criteria include progression on androgen deprivation therapy, 2 or more high-risk features for early (LDH ≥ULN; ALP ≥ULN; albumin <35 g/L; M1 disease at diagnosis; <3 years from initial diagnosis to randomisation; >5 bone metastases; visceral metastases; PSA doubling time <84 days; pain requiring opiates >14 days; prior abiraterone), no prior treatment with a novel androgen signalling inhibitor (except abiraterone), no prior chemotherapy for mCRPC, and PSMA-avid disease on positron emission tomography (PET) with 68Ga-PSMA. Participants are randomly assigned (1:1) enzalutamide 160 mg daily or enzalutamide 160 mg daily plus LuPSMA 7.5 GBq on days 15 and 57. Two subsequent doses of Lu-PSMA will be administered if the 68Ga-PSMA PET on day 92 shows persistent PSMA expression in the tumour. Imaging assessments include CT and technetium bone scan at baseline, day 99, then every 12 weeks; 68Ga-PSMA-11 PET at baseline, days 15, 92, and first progression; and 18F FDG PET at baseline and first progression. Translational samples including circulating tumour cells (CTCs), circulating tumour DNA (ctDNA) and biopsies (optional) will be collected at baseline, day 92, and first progression. The primary endpoint is PSA progression-free survival (PSA-PFS). Secondary endpoints include radiological-PFS, PSA-response rate, pain response and PFS, clinical-PFS, overall survival, health related quality of life, adverse events, and cost-effectiveness. Correlative studies include identification of prognostic and predictive biomarkers from 68Ga-PSMA, 18F FDG PET/CT, CTCs, and ctDNA. A sample size of 160 provides 80% power with a 2-sided type 1-error rate of 5% to detect a HR of 0.625 assuming a median PSA-PFS of 5 months with enzalutamide alone. Accrual was 5 on 13 October 2020. ENZA-p is an investigator-initiated, academic trial led by ANZUP in collaboration with the NHMRC Clinical Trials Centre, University of Sydney. Clinical trial information: NCT04419402.

First-in-human phase 1 PET study of CTT1057, a novel 18F-labeled imaging agent targeting prostate specific membrane antigen (PSMA) in prostate cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16562-e16562
Author(s):  
Rahul Raj Aggarwal ◽  
Spencer Behr ◽  
Youngho Seo ◽  
Kenneth Gao ◽  
Vahid Rahanfar ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Salivary Gland ◽  
Phase 1 ◽  
Imaging Study ◽  
Preliminary Evidence ◽  
Tracer Uptake ◽  
Whole Body ◽  
Castration Resistant Prostate Cancer ◽  
Comparison Results ◽  
Psma Pet

e16562 Background: Urea-based 68Ga-PSMA PET is increasingly being utilized for diagnostic purposes in prostate cancer; however high tracer uptake within the salivary gland and kidney may be dose-limiting upon translation to radiotherapy. We developed a novel 18F labeled agent, CTT1057, a PSMA inhibitor based on a phosphoramidate scaffold with nanomolar and irreversible binding affinity to PSMA and robust internalization, and performed a first-in-human imaging study. Methods: Patients (pts) with metastatic castration resistant prostate cancer (mCRPC) were eligible. 10 mCi (370 MBq) of CTT1057 was injected and whole body PET/MR imaging (SIGNA PET/MR, GE) was performed 60 min post-injection. SUVmean in normal organs was recorded by drawing a 1 cm3 volume-of-interest. SUVmax was determined for each PSMA-avid metastasis. 10 randomly selected, consecutive 68Ga-PSMA PET scans from an independent cohort were used for descriptive comparison. Results: 5 pts with mCRPC were enrolled, with average age of 66 years (range 35–85) and median PSA of 12.2 (range 0.73 – 157.7). 55 PSMA-avid metastases were seen, including 37 osseous (average SUVmax = 8.1 ± 4.4), 15 lymph node (SUVmax = 11.0 ± 6.1), and 3 pulmonary (SUVmax = 3.2 ± 0.6). 31 (83%) and 12 (32%) of the PSMA-avid osseous lesions were visible on CT and bone scan, respectively. The mean short axis diameter of PSMA-avid lymph nodes was 0.7 ± 0.4 cm. Tumor-to-background ratios (liver, muscle, blood pool) were 2.8 ± 2.3, 14.9 ± 11.6, and 3.2 ± 2.4, respectively. SUVmean in salivary gland and kidney were 3.6 ± 0.4 and 9.1 ± 0.8 for CTT1057 and 15.8 ± 2.7 and 35.9 ± 9.6 for 68Ga-PSMA, respectively. No tracer-related adverse events were observed and radiation dose estimates for organs and whole-body effective dose were within acceptable limits. Conclusions: 18F-labeled CTT1057 targeting PSMA, detected mCRPC lesions in the soft tissue and bone at greater sensitivity than conventional imaging. CTT1057 distribution of uptake was similar to urea-based PSMA imaging, with preliminary evidence of lower uptake in the salivary gland and kidney. Further clinical studies of the CTT1057 backbone as a diagnostic and therapeutic agent in mCRPC are warranted. Clinical trial information: NCT02916537.

scholarly journals Concordance between Response Assessment Using Prostate-Specific Membrane Antigen PET and Serum Prostate-Specific Antigen Levels after Systemic Treatment in Patients with Metastatic Castration Resistant Prostate Cancer: A Systematic Review and Meta-Analysis

Diagnostics ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 663
Author(s):  
Sangwon Han ◽  
Sungmin Woo ◽  
Yong-il Kim ◽  
Jae-Lyun Lee ◽  
Andreas G. Wibmer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Systemic Treatment ◽  
Meta Analysis ◽  
Specific Antigen ◽  
Response Evaluation ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Psma Pet ◽  
Psa Response ◽  
Specific Membrane

Prostate-specific membrane antigen positron emission tomography (PSMA PET) has recently gained interest as a promising tool for treatment response evaluation in metastatic castration-resistant prostate cancer (CRPC). We performed a systematic review and meta-analysis assessing the concordance between response evaluation using PSMA PET and serum prostate-specific antigen (PSA) level after systemic treatment and the association between PSMA PET and overall survival in metastatic CRPC patients. PubMed, Embase, and Cochrane library databases were searched until August 2020. Studies that reported the concordance between PSMA PET and PSA response were included. PSMA PET and PSA response evaluation were dichotomized into response vs. non-response to construct two-by-two contingency tables; an ≥30% increase in PSMA PET according to PET Response Criteria in Solid Tumors 1.0 and as an increase in serum PSA level of ≥25% as per Prostate Cancer Working Group 3 guidelines were defined as non-response. The percent agreement rates were pooled using random-effect model. Ten studies (268 patients) were included. The concordance rates ranged 0.50–0.84 with a pooled proportion of 0.73 (95% confidence interval 0.67–0.79). Patients were treated with 177Lu-PSMA therapy in five, chemotherapy in three, 223Ra in one, and more than one type in one study. Various PET parameters were used: the most widely evaluated was PSMA tumor volume (PSMA-TV). Similar proportions were found across different therapeutic agents, PET response parameters, and regarding directionality of discordance (PSA response/PSMA non-response vs. PSMA response/PSA non-response). Two studies reported that a decrease in PSMA-TV was associated with better overall survival. PSMA PET and PSA response assessments were discordant in nearly a fourth of metastatic CRPC patients. Further studies are warranted to establish the clinical meaning of this discordance and define appropriate management for such clinical situation.

scholarly journals Current and potential future role of PSMA-PET in patients with castration-resistant prostate cancer

2018 ◽  
Vol 37 (3) ◽  
pp. 457-467 ◽  
Author(s):  
Christian Daniel Fankhauser ◽  
Cédric Poyet ◽  
Stephanie G. C. Kroeze ◽  
Benedikt Kranzbühler ◽  
Helena I. Garcia Schüler ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Castration Resistant Prostate Cancer ◽  
Future Role ◽  
Castration Resistant ◽  
Psma Pet

Single-lesion PSMA protein expression and response to Lu-177 PSMA therapy in patients with castration-resistant prostate cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5065-5065
Author(s):  
Judith Stangl-Kremser ◽  
Sazan Rasul ◽  
Jeffrey J. Tosoian ◽  
Simpa Salami ◽  
Alexander Zaslavsky ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Protein Expression ◽  
Pet Imaging ◽  
Metastatic Tumor ◽  
Specific Response ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Tumor Tissues ◽  
Psma Pet ◽  
Psma Expression

5065 Background: The recent introduction of Lu-177 PSMA for the treatment of castration-resistant prostate cancer (CRPC) has been met with much excitement. Initial reports of clinical response are promising, despite known inter- and intra-patient molecular heterogeneity. In this study, we examined the utility of PSMA protein expression in metastatic tumor tissues as a predictor of lesion-specific response to Lu-177 PSMA therapy in men with CRPC. Methods: Between 2015-2020, 19 patients with metastases at multiple sites underwent metastatic lesion biopsy, Ga-68 PSMA PET imaging, and subsequent treatment with three cycles of Lu-177 PSMA. A monoclonal anti-PSMA antibody (EPITOMICS (USA), 1:50) was used to semi-quantitatively assess PSMA protein expression in the biopsy specimen. The histoscore (range 0-300) was derived from intensity and extent of the immunohistochemistry staining and was determined by experienced genitourinary pathologists. Imaging evaluation was performed according to the Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) criteria. We assessed the association of the PSMA protein expression in metastatic tumor tissues and the lesion-specific response to Lu-177 PSMA therapy. Results: In 12 patients with biopsy specimens available for staining, PSMA expression correlated with enhancement (SUVmax) of the biopsy site on Ga-68 PSMA PET imaging (rs = 0.63). Of the nine patients with repeat imaging after Lu-177 PSMA therapy, five (55.6%) had a lesion-specific response at the site of biopsy. PSMA expression on immunohistochemistry was unable to accurately predict lesion-specific response in univariable analysis (p = 0.81, 95% CI 94.6-76.6). Among the five men with a lesion-specific response, three (60%) experienced overall progression based on PERCIST. There was no association between lesion-specific response and overall progression (p = 0.64). Conclusions: In patients with multiple metastases, PSMA protein expression from a single site biopsy was not predictive of site-specific Lu-177 PSMA response based on PERCIST. Additional studies are necessary to further interrogate the clinical consequence of PSMA expression heterogeneity in metastatic sites as well as the mechanisms underpinning resistance to Lu-177 PSMA in patients with CRPC.

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