scholarly journals PSMA Theranostics: Current Landscape and Future Outlook

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4023
Author(s):  
Hanbo Zhang ◽  
Stella Koumna ◽  
Frédéric Pouliot ◽  
Jean-Mathieu Beauregard ◽  
Michael Kolinsky
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Treatment Strategies ◽  
Standard Of Care ◽  
Predictive Biomarker ◽  
Psma Pet ◽  
Pet Ct ◽  
Treatment Paradigm ◽  
Theranostic Applications ◽  
Fdg Pet Ct

Introduction: Prostate-specific membrane antigen (PSMA) is a promising novel molecular target for imaging diagnostics and therapeutics (theranostics). There has been a growing body of evidence supporting PSMA theranostics approaches in optimizing the management of prostate cancer and potentially altering its natural history. Methods: We utilized PubMed and Google Scholar for published studies, and clinicaltrials.gov for planned, ongoing, and completed clinical trials in PSMA theranostics as of June 2021. We presented evolving evidence for various PSMA-targeted radiopharmaceutical agents in the treatment paradigm for prostate cancer, as well as combination treatment strategies with other targeted therapy and immunotherapy. We highlighted the emerging evidence of PSMA and fluorodeoxyglucose (FDG) PET/CT as a predictive biomarker for PSMA radioligand therapy. We identified seven ongoing clinical trials in oligometastatic-directed therapy using PSMA PET imaging. We also presented a schematic overview of 17 key PSMA theranostic clinical trials throughout the various stages of prostate cancer. Conclusions: In this review, we presented the contemporary and future landscape of theranostic applications in prostate cancer with a focus on PSMA ligands. As PSMA theranostics will soon become the standard of care for the management of prostate cancer, we underscore the importance of integrating nuclear medicine physicians into the multidisciplinary team.

68Ga-DOTA-Bombesin (68Ga-RM2 or 68Ga-Bombesin) PET versus 68Ga-PSMA PET: A pilot prospective evaluation in patients with biochemical recurrence of prostate cancer.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 331-331
Author(s):  
Andrei Iagaru ◽  
Ryogo Minamimoto ◽  
Steven Lee Hancock ◽  
Erik Mittra ◽  
Andreas Loening ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Renal Clearance ◽  
Biochemical Recurrence ◽  
Conventional Imaging ◽  
Normal Tissues ◽  
Psma Pet ◽  
Pet Ct ◽  
Small Cohort ◽  
Bombesin Receptor ◽  
Fdg Pet Ct

331 Background: Detection of prostate cancer (PC) after biochemical recurrence (BCR) remains a great challenge. RM2 is a synthetic bombesin receptor antagonist, which targets gastrin-releasing peptide receptors (GRPr). PSMA is a membrane antigen expressed on prostate cancer cells. Here we present a comparison of 2 novel PET tracers, 68Ga-RM2 and 68Ga-PSMA, in patients with BCR with prior non-contributory conventional imaging. Methods: Ten men (67-83 year-old; mean ± SD: 74.3 ± 5.9) with BCR PC were imaged with 68Ga-RM2 and 7 of them also had 68Ga-PSMA PET. The SUVmax and SUVmean measurements were recorded in normal tissues and areas of uptake outside the expected physiologic biodistribution. Results: All 7 patients who had both scans had rising PSA (range: 3.5-36.5 ng/mL; mean±SD: 13.5 ± 11.5) and non-contributory conventional imaging (CT, MRI, 18F FDG PET/CT, 18F NaF PET/CT, 99mTc MDP bone scan). 68Ga-PSMA had the highest physiologic uptake in the salivary glands and small bowel, with hepatobiliary and renal clearance noted, while 68Ga-RM2 had the highest physiologic uptake in the pancreas, with renal clearance noted. Uptake values uptake outside the expected physiologic biodistribution were not statistically different between 68Ga-PSMA and 68Ga-RM2. 68Ga-PSMA localized in a lymph node and seminal vesicle in one patient with no abnormal 68Ga-RM2 uptake. In 2 patients abdominal peri-aortic lymph nodes were more easily visualized by 68Ga-RM2 due to lack of interference by radioactivity accumulation in the small intestine. Conclusions: 68Ga-PSMA and 68Ga-RM2 have distinct biodistribution in this small cohort of patients with BCR PC. High uptake in multiple areas outside the expected physiologic biodistribution suggests that both 68Ga-PSMA and 68Ga-RM2 are promising PET radiopharmaceuticals for localization of disease in patients with BCR PC and non-contributory conventional imaging. The differences in target density, biodistribution and clearance pathways may result in the superiority of one of the two tracers in different patients. 68Ga-RM2 shows similar sensitivity to 68Ga-PSMA and has the potential for being FDA-approved in the future. Clinical trial information: NCT02440308.

scholarly journals Concomitant Prostate Cancer and Hodgkin Lymphoma: A Differential Diagnosis Guided by a Combined 68Ga-PSMA-11 and 18F-FDG PET/CT Approach

Medicina ◽  
2021 ◽  
Vol 57 (9) ◽  
pp. 975
Author(s):  
Alberto Miceli ◽  
Mattia Riondato ◽  
Francesca D’Amico ◽  
Maria Isabella Donegani ◽  
Nataniele Piol ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Hodgkin Lymphoma ◽  
Fdg Pet ◽  
Standardized Uptake Value ◽  
Diagnostic Process ◽  
Psma Pet ◽  
Pet Ct ◽  
18F Fdg ◽  
Fdg Pet Ct ◽  
Tumor Entities

Here we report the case of concomitant favorable-risk prostate cancer and Hodgkin Lymphoma in a 38-year old male. 68Ga-Prostate Specific Membrane Antigen-11 Positron Emission Tomography/Computed Tomography (68Ga-PSMA-11 PET/CT) was performed for staging purposes, showing the focal PSMA prostatic uptake as well as the presence of enlarged low-PSMA expressing mediastinal lymphadenopathies, thus raising the suspicion of another malignancy. A subsequent 18F-Fluorodeoxyglucose (18F-FDG) PET/CT demonstrated a high FDG-avidity by mediastinal lymphadenopathies as opposed to the low prostate cancer FDG uptake. Of note, both tumor entities were clearly detected by the two scans. However, different ranges in terms of Maximum Standardized Uptake Value (SUVmax) uptake allowed the discrimination between the two tumor entities. At the subsequent mediastinal lymph nodal biopsy, the coexistence of Hodgkin lymphoma was documented. The present case suggests that even if specific for prostate cancer, 68Ga-PSMA-11 PET/CT may raise the suspicion of other concurrent malignancies thanks to its non-receptor bounding mechanism. Further, it shows that in certain cases, the combination of 18F-FDG and 68Ga-PSMA PET/CT imaging may non-invasively guide the clinical management, optimizing the diagnostic process and the subsequent therapeutic interventions.

scholarly journals Incremental costs of prostate cancer trials: Are clinical trials really a burden on a public payer system?

2013 ◽  
Vol 7 (3-4) ◽  
pp. e231-6 ◽  
Author(s):  
Britney Jones ◽  
Rachel Syme ◽  
Misha Eliasziw ◽  
Bernhard J. Eigl
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Resource Utilization ◽  
Treatment Strategies ◽  
Standard Of Care ◽  
Cost Distribution ◽  
Observational Cohort ◽  
Cancer Trials ◽  
Public Payer ◽  
The Cost

Introduction: Clinical trials are a critical component of improving cancer prevention and treatment strategies. However, the perception that patients enrolled in trials consume more resources than those receiving the standard-of-care (SOC) has contributed to an increasingly research-averse environment. Current economic data pertaining to the per-patient costs of prostate cancer trials relative to SOC treatment are limited.Methods: A retrospective observational cohort study was conducted to compare costs incurred by 59 prostate cancer patients participating in a mix of industry and non-industry sponsored clinical trials with costs incurred by an equal number of eligible nonparticipants who received SOC over a year. Resource utilization was tracked and quantified to standardized price templates.Results: No difference in overall resource utilization was seen between trial and SOC patients (two-tailed t-test, n = 118, p = 0.99). Variability in the types of resources used by each group indicated that, while trial patients may take up significantly more clinic time (p = 0.001) and undergo more tests and procedures (p = 0.001), SOC patients are more likely to receive other costly interventions, such as radiation therapy (p < 0.001). Other variables (e.g., pathology, diagnostic imaging, prescribed therapies) were statistically indistinguishable between groups.Conclusion: This study revealed differences in the cost distribution of patients enrolled in clinical trials versus those receiving SOC, which could be used to improve resource allocation. The lack of evidence for a difference in overall cost provides an argument for payers to more fully support clinical research without fear of adverse financial consequences. Further analysis is required.

UpFrontPSMA: A randomized phase II study of sequential 177Lu-PSMA617 and docetaxel versus docetaxel in metastatic hormone-naïve prostate cancer (mHNPC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. TPS180-TPS180
Author(s):  
Arun Azad ◽  
Nattakorn Dhiantravan ◽  
Louise Emmett ◽  
Anthony M. Joshua ◽  
Ian Vela ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Disease Progression ◽  
Whole Blood ◽  
Fdg Pet ◽  
Standard Of Care ◽  
High Volume ◽  
Tumour Tissue ◽  
Pet Ct ◽  
Fdg Pet Ct

TPS180 Background: 177Lu‐PSMA-617 (Lu-PSMA) is a radiolabeled small-molecule that binds with high affinity to PSMA enabling highly targeted delivery of beta radiation to prostate cancer cells. In metastatic castration-resistant prostate cancer, Lu-PSMA showed superior activity to Cabazitaxel in the TheraP trial. Although androgen deprivation therapy (ADT) + Docetaxel is a standard of care for de novo high-volume mHNPC, outcomes remain sub-optimal for many patients. We hypothesize that Lu-PSMA prior to docetaxel will achieve a higher undetectable PSA rate at 12 months compared to docetaxel alone in men with newly-diagnosed high-volume mHNPC. Methods: UpFrontPSMA is an open label, randomized, stratified, 2-arm, multi-center, phase 2 clinical trial recruiting 140 patients at 11 Australian centers. Key eligibility criteria include histological diagnosis of prostate cancer within 12 weeks, PSA > 10ng/ml at diagnosis, < 4 weeks on ADT, and high-volume (≥ 4 bone metastases with ≥ 1 outside the axial skeleton, and/or visceral metastases), PSMA-avid disease on 68Ga-PSMA-11 PET/CT with no major discordance on 18FDG-PET/CT. Patients will be randomized 1:1 to the experimental arm (Lu-PSMA 7.5 GBq q6w x 2 cycles followed 6 weeks later by docetaxel 75mg/m2 q3w x 6 cycles), or standard-of-care Arm (docetaxel alone). All patients will receive continuous ADT. Assessments will be done every 3 weeks during study treatment, and then every 6-12 weeks until unequivocal disease progression. CT and whole body bone scan will be performed at baseline and every 12 weeks, 68Ga-PSMA-11 PET/CT at baseline and 12 weeks, and 18FDG-PET/CT at baseline and 12 weeks (if applicable). Correlative samples will include optional tumour tissue (baseline and disease progression), and serial plasma/whole blood collection. The primary endpoint is undetectable PSA (≤ 0.2 ng/ml) at 12 months. Secondary endpoints are safety, time to castration resistance, PSA-progression-free-survival (PSA-PFS), radiographic PFS, radiographic response rates, early PSMA-PET response rates, quality of life and overall survival. Exploratory endpoints are prognostic and predictive value of PET-derived parameters and of biomarkers identified in plasma/whole blood/tumour tissue. The study will have 85% power to reject the null hypothesis if the true 12 month undetectable PSA rate in the experimental Arm is 50%. The power calculation assumes no more than 10 patients (7%) of the 140 patients will be unevaluable or lost to follow-up in 1 year, 5% alpha and two-sided test for proportions. As of October 13, 2020, accrual stands at 4. UpFrontPSMA is an investigator-led, academic trial sponsored by Peter MacCallum Cancer Centre in collaboration with ANZUP Cancer Trials Group with study coordination provided by the Centre for Biostatistics and Clinical Trials (BaCT) Clinical trial information: NCT04343885.

scholarly journals The Evolving Role of 18F-FDG PET/CT in Diagnosis and Prognosis Prediction in Progressive Prostate Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Kai Shen ◽  
Bo Liu ◽  
Xiang Zhou ◽  
Yiyi Ji ◽  
Lei Chen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Fdg Pet ◽  
Early Stage ◽  
High Specificity ◽  
Tumor Burden ◽  
Castration Resistant Prostate Cancer ◽  
Positron Emission ◽  
Psma Pet ◽  
Pet Ct ◽  
Fdg Pet Ct

Positron emission tomography/computed tomography (PET/CT) is widely used in prostate cancer to evaluate the localized tumor burden and detect symptomatic metastatic lesions early. 18F-FDG is the most used tracer for oncologic imaging, but it has limitations in detecting early-stage prostate cancer. 68Ga-PSMA is a new tracer that has high specificity and sensibility in detecting local and metastatic tumors. But with the progression of prostate cancer, the enhancement of glucose metabolism in progressive prostate cancer provides a chance for 18F-FDG. This review focuses on PET/CT in the detection and prognosis of prostate cancer, summarizing the literature on 18F-FDG and 68Ga-PSMA in prostate cancer and highlighting that 18F-FDG has advantages in detecting local recurrence, visceral and lymph node metastases compared to 68Ga-PSMA in partial progressive prostate cancer and castration-resistant prostate cancer patients. We emphasize 18F-FDG PET/CT can compensate for the weakness of 68Ga-PSMA PET/CT in progressive prostate cancer.

The Added Value of 18F-FDG PET/CT Compared with 68Ga-PSMA PET/CT in Patients with Castration-Resistant Prostate Cancer

2022 ◽  
Vol 63 (1) ◽  
pp. 69-75
Author(s):  
Ruohua Chen ◽  
Yining Wang ◽  
Yinjie Zhu ◽  
Yiping Shi ◽  
Lian Xu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Fdg Pet ◽  
Added Value ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Psma Pet ◽  
Pet Ct ◽  
18F Fdg ◽  
Fdg Pet Ct

Final results of a phase I/II prospective dose escalation trial evaluating safety and efficacy of combination 177Lu PSMA 617 and NOX66 in men with end-stage metastatic castration-resistant prostate cancer (LuPIN trial).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 103-103
Author(s):  
Sarennya Pathmanandavel ◽  
Megan Crumbaker ◽  
Andrew On Wah Yam ◽  
Christopher Rofe ◽  
Bao Ho ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Fdg Pet ◽  
Nadh Oxidase ◽  
Castration Resistant Prostate Cancer ◽  
Safety And Efficacy ◽  
Quantitative Pet ◽  
Pain Scores ◽  
Psma Pet ◽  
Pet Ct ◽  
Fdg Pet Ct

103 Background: 177LuPSMA – 617 is a promising therapy for metastatic castrate-resistant prostate cancer (mCRPC). However, treatment resistance occurs frequently and synergistic combination therapy may improve outcomes. We combined 177LuPSMA – 617 with idronoxil (NOX66), an inhibitor of external NADH oxidase type 2 with radio-sensitizing properties. We present the final safety and efficacy results. Methods: Men with progressive mCRPC after androgen signalling inhibition (ASI) and taxane chemotherapy were enrolled. Key inclusion criteria were: PSMA PET/CT intensity SUV max > 15 with no discordant disease on FDG PET/CT, haemoglobin > 100g/L, platelets > 100x109/L and eGFR > 40mls/min. Enrolled patients received up to six doses of 177 Lu-PSMA 617 (7.5Gbq) day 1 every 6 weeks in combination with NOX66 days 1-10 each cycle. Cohort 1 (n = 8) received 400mg NOX66. Following safety reviews the doses were escalated in cohorts 2 (n = 24) and 3 (n = 24) to 800mg and 1200mg of NOX66, respectively. Blood samples were prospectively collected for androgen receptor splice variant 7 (ARV7) expression. PSMA and FDG PET/CT were performed at study entry and on progression. The primary outcomes were safety and tolerability; the secondary outcomes evaluated were efficacy, pain scores, and quality of life. Results: Of the 56 men enrolled, all had received prior treatment with ASI and docetaxel, and 95% (53/56) had prior cabazitaxel. 96% (54/56) patients received ≥2 cycles and 46% (26/56) completed six cycles of treatment. Adverse events are summarized in the table below. PSA responses were as follows: 86% (48/56) had any PSA reduction and 61% (34/56) had > 50% PSA reduction. 84% (47/56) have had PSA progression to date with median follow up 18.9 months (95% CI 11.9-25.8). Median PSA PFS was 7.5 months (95% CI 6.0-9.0). 55% (31/56) have died and median overall survival was 19.7 months (95% CI 10.7-28.7). 34/56 men had baseline pain scores ≥3, of whom 53% (18/34) had significant reduction in pain indicators. There was no correlation between quantitative PET results and either PSA > 50% response, PSA PFS or OS. Conclusions: The combination of 177 Lu-PSMA 617 + NOX66 appears safe and efficacious in men with heavily pre-treated mCRPC. Exploratory analysis of ARV7 expression and quantitative PET imaging markers of treatment response and resistance is in progress. Clinical trial information: ACTRN12618001073291. [Table: see text]

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