Publications by authors named "Wolfgang P Fendler"

78 Publications

Prostate-specific Membrane Antigen PET in Prostate Cancer.

Radiology 2021 Mar 30:202771. Epub 2021 Mar 30.

From the Department of Radiology and Biomedical Imaging (C.L.H., S.C.B., T.A.H.) and Helen Diller Family Comprehensive Cancer Center (S.C.B., T.A.H.), University of California San Francisco, 505 Parnassus Ave, M391, San Francisco, CA 94143; Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, Md (A.S., S.P.R.); Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, Calif (J.C.); Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany (W.P.F.); Department of Nuclear Medicine, Technical University of Munich, Munich, Germany (M.E.); Department of Theranostics and Nuclear Medicine, St. Vincent's Hospital, Sydney, Australia (L.E.); Prostate Theranostics and Imaging Centre of Excellence (ProsTIC), Peter MacCallum Cancer Centre, Melbourne, Australia (M.S.H.); and Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia (M.S.H.).

Prostate-specific membrane antigen (PSMA)-targeted radiopharmaceuticals are playing a large role at the time of initial staging and biochemical recurrence for localizing prostate cancer, as well as in other emerging clinical settings. PSMA PET has demonstrated increased detection rate compared with conventional imaging and has been shown to change management plans in a substantial percentage of cases. The aims of this narrative review are to highlight the development and clinical impact of PSMA PET radiopharmaceuticals, to compare PSMA to other agents such as fluorine 18 fluciclovine and carbon 11 choline, and to highlight some of the individual PSMA PET agents that have contributed to the advancement of prostate cancer imaging.
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http://dx.doi.org/10.1148/radiol.2021202771DOI Listing
March 2021

Just another "Clever Hans"? Neural networks and FDG PET-CT to predict the outcome of patients with breast cancer.

Eur J Nucl Med Mol Imaging 2021 Mar 5. Epub 2021 Mar 5.

Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital, Hufelandstraße 55, 45147, Essen, Germany.

Background: Manual quantification of the metabolic tumor volume (MTV) from whole-body F-FDG PET/CT is time consuming and therefore usually not applied in clinical routine. It has been shown that neural networks might assist nuclear medicine physicians in such quantification tasks. However, little is known if such neural networks have to be designed for a specific type of cancer or whether they can be applied to various cancers. Therefore, the aim of this study was to evaluate the accuracy of a neural network in a cancer that was not used for its training.

Methods: Fifty consecutive breast cancer patients that underwent F-FDG PET/CT were included in this retrospective analysis. The PET-Assisted Reporting System (PARS) prototype that uses a neural network trained on lymphoma and lung cancer F-FDG PET/CT data had to detect pathological foci and determine their anatomical location. Consensus reads of two nuclear medicine physicians together with follow-up data served as diagnostic reference standard; 1072 F-FDG avid foci were manually segmented. The accuracy of the neural network was evaluated with regard to lesion detection, anatomical position determination, and total tumor volume quantification.

Results: If PERCIST measurable foci were regarded, the neural network displayed high per patient sensitivity and specificity in detecting suspicious F-FDG foci (92%; CI = 79-97% and 98%; CI = 94-99%). If all FDG-avid foci were regarded, the sensitivity degraded (39%; CI = 30-50%). The localization accuracy was high for body part (98%; CI = 95-99%), region (88%; CI = 84-90%), and subregion (79%; CI = 74-84%). There was a high correlation of AI derived and manually segmented MTV (R = 0.91; p < 0.001). AI-derived whole-body MTV (HR = 1.275; CI = 1.208-1.713; p < 0.001) was a significant prognosticator for overall survival. AI-derived lymph node MTV (HR = 1.190; CI = 1.022-1.384; p = 0.025) and liver MTV (HR = 1.149; CI = 1.001-1.318; p = 0.048) were predictive for overall survival in a multivariate analysis.

Conclusion: Although trained on lymphoma and lung cancer, PARS showed good accuracy in the detection of PERCIST measurable lesions. Therefore, the neural network seems not prone to the clever Hans effect. However, the network has poor accuracy if all manually segmented lesions were used as reference standard. Both the whole body and organ-wise MTV were significant prognosticators of overall survival in advanced breast cancer.
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http://dx.doi.org/10.1007/s00259-021-05270-xDOI Listing
March 2021

Imaging Inflammation with Positron Emission Tomography.

Biomedicines 2021 Feb 19;9(2). Epub 2021 Feb 19.

Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Hufelandstraße 55, D-45147 Essen, Germany.

The impact of inflammation on the outcome of many medical conditions such as cardiovascular diseases, neurological disorders, infections, cancer, and autoimmune diseases has been widely acknowledged. However, in contrast to neurological, oncologic, and cardiovascular disorders, imaging plays a minor role in research and management of inflammation. Imaging can provide insights into individual and temporospatial biology and grade of inflammation which can be of diagnostic, therapeutic, and prognostic value. There is therefore an urgent need to evaluate and understand current approaches and potential applications for imaging of inflammation. This review discusses radiotracers for positron emission tomography (PET) that have been used to image inflammation in cardiovascular diseases and other inflammatory conditions with a special emphasis on radiotracers that have already been successfully applied in clinical settings.
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http://dx.doi.org/10.3390/biomedicines9020212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922638PMC
February 2021

We Can Make a Difference: Investigator-driven Prostate-specific Membrane Antigen Radiotheranostics for Prostate Cancer.

Eur Urol Focus 2021 Mar 18;7(2):227-228. Epub 2021 Feb 18.

Ahmanson Translational Theranostics Division, Department of Molecular & Medical Pharmacology, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California-Los Angeles, Los Angeles, CA, USA; Institute of Urologic Oncology, University of California-Los Angeles, Los Angeles, CA, USA; Physics and Biology in Medicine Interdepartmental Graduate Program, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.

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http://dx.doi.org/10.1016/j.euf.2021.02.002DOI Listing
March 2021

[Ga]Ga-PSMA-11 PET/CT improves tumor detection and impacts management in patients with hepatocellular carcinoma (HCC).

J Nucl Med 2021 Jan 28. Epub 2021 Jan 28.

Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Germany.

Hepatocellular carcinoma (HCC) is the sixth most prevalent cancer and the third most frequent cause of cancer-related death. A growing number of local and systemic therapies are available, and accurate staging is critical for management decisions. We assessed the impact of neovasculature imaging by Ga-Ga-PSMA-11 PET/CT on disease staging, prognostic groups and management of patients with HCC compared to staging with computed tomography (CT). Forty patients who received imaging with Ga-Ga-PSMA-11 PET/CT for HCC staging between September 2018 and September 2019 were retrospectively included. Management pre- and post-PET scan was assessed by standardized surveys. Presence of HCC was evaluated by three blinded readers on a per-patient and per-region basis for PET/CT (PET criteria) and multi-phase contrast-enhanced CT (CT criteria) in separate sessions. Lesions were validated by follow-up imaging or histopathology, and progression-free survival (PFS) was recorded. Endpoints were detection rate and positive predictive value (PPV) for Ga-Ga-PSMA-11 PET vs. CT, inter-reader reproducibility, and changes in stage, prognostic groups and management plans. Median age was 65 years (range, 37-81), median Child-Pugh score was 5 (range, 5-9). Most patients were treatment naïve (27 of 40, 67.5%). The sensitivity of PET vs. CT to identify liver lesions for patients with lesion validation was 31/32 (97%) for both modalities, while it was 6/6 (100%) vs. 4/6 (67%) for extra-hepatic lesions. PET and CT each had a PPV of 100% at the liver level. PET vs. CT stage was congruent in 30/40 (75%) patients; upstaging was seen in 8/40 patients (20%), while 2/40 (5%) had downstaging by PET. Intended management changed in 19/40 patients (47.5%); 9/19 of these patients were found to have detectable distant metastases (47.4%) and assigned stage 4 disease, the majority of whom were shifted to systemic therapy (8 of 9, 89%). Two patients underwent Lu-Lu-PSMA-617 radioligand therapy. Median PFS was 5.2 months for the entire cohort; 5.3 months for PET M0, and 4.7 months for PET M1 patients, respectively. Ga-Ga-PSMA-11 PET demonstrated higher accuracy than CT in the detection of HCC metastases and was associated with management change in about half of the patient cohort.
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http://dx.doi.org/10.2967/jnumed.120.257915DOI Listing
January 2021

Prostate-specific Membrane Antigen-based Imaging of Castration-resistant Prostate Cancer.

Eur Urol Focus 2021 Mar 20;7(2):279-287. Epub 2021 Jan 20.

West German Cancer Center; Department of Urology, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany.

Context: Positron emission tomography (PET) targeting prostate-specific membrane antigen (PSMA) has unprecedented accuracy for localization of initial or recurrent prostate cancer (PC). There is now growing evidence regarding the value of PSMA-PET in patients with advanced PC.

Objective: To review the value of PSMA-PET/computed tomography (CT) in the context of castration-resistant PC (CRPC).

Evidence Acquisition: A search of the PubMed database using the terms "PSMA PET castration resistant prostate cancer" (years 2011-2020) was performed. Reviews, case reports/series, non-English articles, preclinical studies, access-restricted studies, and studies on PSMA radioligand therapy without further analysis of PSMA-PET parameters were subsequently excluded.

Evidence Synthesis: Compared to conventional imaging, PSMA-PET better identifies the true extent of CRPC, especially nonmetastatic CRPC. The clinical benefit of this stage migration is still unclear and needs to be evaluated in further studies. High accuracy of PSMA-PET holds promise for better, PET-guided metastasis-directed treatment in patients with oligometastatic CRPC. PSMA-PET is an essential eligibility criterion for [Lu]-PSMA theranostic applications. Preliminary evidence indicates the value of PSMA-PET for the assessment of treatment responses.

Conclusions: Among other applications, PSMA-PET offers more precise staging for nonmetastatic CRPC. In particular, target localization for metastasis-directed therapy and target expression assessment for PSMA radioligand therapy also hold promise. Potential translation of this diagnostic tool into an oncologic benefit needs to be defined in future trials.

Patient Summary: This review describes how prostate-specific membrane antigen positron emission tomography (PSMA-PET), a new sensitive imaging tool for prostate cancer, might help to guide clinicians in making treatment decisions for advanced prostate cancer.
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http://dx.doi.org/10.1016/j.euf.2021.01.002DOI Listing
March 2021

Oliver Sartor Talks with Thomas A. Hope, Jeremie Calais, and Wolfgang P. Fendler About FDA Approval of PSMA.

J Nucl Med 2021 02;62(2):146-148

Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany.

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http://dx.doi.org/10.2967/jnumed.120.261834DOI Listing
February 2021

Update from PSMA-SRT Trial NCT03582774: A Randomized Phase 3 Imaging Trial of Prostate-specific Membrane Antigen Positron Emission Tomography for Salvage Radiation Therapy for Prostate Cancer Recurrence Powered for Clinical Outcome.

Eur Urol Focus 2021 Mar 30;7(2):238-240. Epub 2020 Dec 30.

Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA; Institute of Urologic Oncology, University of California, Los Angeles, Los Angeles, CA, USA; Physics and Biology in Medicine Interdepartmental Graduate Program, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.

The purpose of this randomized trial is to evaluate the success rate of salvage radiation therapy for recurrence of prostate cancer after radical prostatectomy, with and without planning based on prostate-specific membrane antigen positron emission tomography/computed tomography. Enrollment has been completed and patients are being followed for 5yr.
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http://dx.doi.org/10.1016/j.euf.2020.12.009DOI Listing
March 2021

PSMA PET total tumor volume predicts outcome of patients with advanced prostate cancer receiving [Lu]Lu-PSMA-617 radioligand therapy in a bicentric analysis.

Eur J Nucl Med Mol Imaging 2021 Apr 24;48(4):1200-1210. Epub 2020 Sep 24.

Department of Nuclear Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1, D-48149, Münster, Germany.

Introduction: [Lu]Lu-PSMA-617 (Lu-PSMA) radioligand therapy is an emerging treatment option for patients with end-stage prostate cancer. However, response to Lu-PSMA therapy is only achieved in approximately half of patients. It is clinically important to identify patients at risk of poor outcome. Therefore, the aim of this study was to evaluate pretherapeutic PSMA PET derived total tumor volume and related metrics as prognosticators of overall survival in patients receiving Lu-PSMA therapy.

Methods: A total number of 110 patients form the Departments of Nuclear Medicine Münster and Essen were included in this retrospective analysis. Baseline PSMA PET-CT was available for all patients. Employing a previously published approach, all tumor lesions were semi-automatically delineated in PSMA PET-CT acquisitions. Total lesion number, total tumor volume (PSMA-TV), total lesion uptake (PSMA-TLU = PSMA-TV * SUV), and total lesion quotient (PSMA-TLQ = PSMA-TV / SUV were quantified for each patient. Log2 transformation was used for regressions.

Results: Lesion number, PSMA-TV, and PSMA-TLQ were prognosticators of overall survival (HR = 1.255, p = 0.009; HR = 1.299, p = 0.005; HR = 1.326, p = 0.002). In a stepwise backward Cox regression including lesion number, PSMA-TV, PSA, LDH, and PSMA-TLQ, only the latter two remained independent and statistically significant negative prognosticators of overall survival (HR = 1.632, p = 0.011; HR = 1.239, p = 0.024). PSMA-TLQ and LDH were significant negative prognosticators in multivariate Cox regression in contrast to PSA value.

Conclusion: PSMA-TV was a statistically significant negative prognosticator of overall survival in patients receiving Lu-PSMA therapy. PSMA-TLQ was an independent and superior prognosticator of overall survival compared with PSMA-TV.
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http://dx.doi.org/10.1007/s00259-020-05040-1DOI Listing
April 2021

Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography Compared with Conventional Imaging for Initial Staging of Treatment-naïve Intermediate- and High-risk Prostate Cancer: A Retrospective Single-center Study.

Eur Urol Oncol 2020 Sep 18. Epub 2020 Sep 18.

Institute of Urologic Oncology (IUO), Department of Urology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA; Ahmanson Translational Imaging Division, Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA; Physics & Biology in Medicine Interdepartmental Graduate Program, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.

Background: The role of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) imaging in the initial staging of men with prostate cancer (PCa) has yet to be evaluated adequately.

Objective: To investigate the concordance of PSMA PET/CT with conventional imaging (CI) with cross-sectional abdominopelvic and/or radionuclide bone imaging in the initial staging of patients with treatment-naïve PCa.

Design, Setting, And Participants: We performed a post hoc retrospective cohort study of patients enrolled in a prospective single-arm trial (NCT03368547). We included patients with intermediate-risk (IR) and high-risk (HR) PCa who underwent PSMA PET/CT within 6 mo of CI. Patients with any treatment prior to PSMA PET/CT were excluded. Patient- and tumor-specific data, and imaging findings were obtained.

Outcome Measurements And Statistical Analysis: Our primary outcome measurement was the concordance rate of PSMA PET/CT with CI for the identification of N, M1a, M1b, and M1c disease. Descriptive statistics were used.

Results And Limitations: A total of 168 patients with treatment-naïve IR and HR PCa met the inclusion criteria. HR disease accounted for 124/168 (73.8%) patients. The median prostate-specific antigen was 11.4 (6.8-24.6)ng/ml. The rates of nonconcordance between PSMA PET/CT and CI were 34/162 (21.0%), 5/70 (7.1%), 8/92 (8.7%), and 1/71 (1.4%) for N, M1a, M1b, and M1c disease, respectively. PSMA PET/CT assigned a higher stage in 37/168 (22.0%) patients and a lower stage in 12/170 (7.1%) patients. In a subset of 50 patients treated with radical prostatectomy and pelvic lymph node dissection, the prevalence of PSMA PET/CT-positive and that of CI-positive nodal disease were 14% and 4%, and the false negative rates were 30% and 32%, respectively. The principal limitations of this study include the heterogeneity in CI modalities and the 6-mo time frame between CI and PSMA PET.

Conclusions: PSMA PET/CT imaging may serve as a valuable tool in the initial staging of treatment-naïve IR and HR PCa.

Patient Summary: We evaluated how prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) compared with standard imaging (such as computed tomography, bone scan, and prostate magnetic resonance imaging) for initial staging of patients with prostate cancer. Our findings suggest that PSMA PET/CT may detect and rule out more metastatic lesions, which could prove valuable in guiding treatment.
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http://dx.doi.org/10.1016/j.euo.2020.08.012DOI Listing
September 2020

PSMA-PET identifies PCWG3 target populations with superior accuracy and reproducibility when compared to conventional imaging: a multicenter retrospective study.

J Nucl Med 2020 Sep 11. Epub 2020 Sep 11.

Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany.

Prostate-specific membrane antigen (PSMA)-ligand positron-emission-tomography (PSMA-PET) is potentially useful for screening of castration resistant prostate cancer (CRPC) clinical trial target populations. We investigated the impact of PSMA-PET on Prostate Cancer Clinical Trials Working Group 3 (PCWG3) clinical subtype classification when compared to conventional imaging (CI). Multicenter retrospective study enrolling patients with (a) PSMA-PET for CRPC, (b) PSA values ≥1 ng/mL and (c) CI, i.e. CT plus bone scan or whole-body MRI. Clinical PCWG3 subtype was determined for PET vs. CI by three blinded readers. 67 patients were included and PSMA-PET led to up-staging in 15% (10/67) of patients, of these 6/10 (60%) had CI non-metastatic CRPC. PSMA-PET resulted in down-staging in 15% (10/67) of patients. Agreement for PET vs. CI PCWG3 clinical subtype was 0.81 vs. 0.51, 0.74 vs. 0.47, 0.95 vs. 0.72, or 0.59 vs. 0.66 for local, nodal, bone, or visceral disease, respectively. PSMA-PET demonstrated major concordance with CI for per-patient PCWG3 clinical subtype and should be implemented in future CRPC clinical trial screening procedures.
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http://dx.doi.org/10.2967/jnumed.120.246603DOI Listing
September 2020

False positive PSMA PET for tumor remnants in the irradiated prostate and other interpretation pitfalls in a prospective multi-center trial.

Eur J Nucl Med Mol Imaging 2021 Feb 17;48(2):501-508. Epub 2020 Aug 17.

Departments of Radiology and Biomedical Imaging and Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, USA.

Purpose: Readers need to be informed about potential pitfalls of [Ga]Ga-PSMA-11 PET interpretation.

Methods: Here we report [Ga]Ga-PSMA-11 PET findings discordant with the histopathology/composite reference standard in a recently published prospective trial on 635 patients with biochemically recurrent prostate cancer.

Results: Consensus reads were false positive in 20 regions of 17/217 (8%) patients with lesion validation. Majority of the false positive interpretations (13 of 20, 65%) occurred in the context of suspected prostate (bed) relapse (T) after radiotherapy (n = 11); other false positive findings were noted for prostate bed post prostatectomy (T, n = 2), pelvic nodes (N, n = 2), or extra pelvic lesions (M, n = 5). Major sources of false positive findings were PSMA-expressing residual adenocarcinoma with marked post-radiotherapy treatment effect. False negative interpretation occurred in 8 regions of 6/79 (8%) patients with histopathology validation, including prostate (bed) (n = 5), pelvic nodes (n = 1), and extra pelvic lesions (n = 2). Lesions were missed mostly due to small metastases or adjacent bladder/urine uptake.

Conclusion: [Ga]Ga-PSMA-11 PET at biochemical recurrence resulted in less than 10% false positive interpretations. Post-radiotherapy prostate uptake was a major source of [Ga]Ga-PSMA-11 PET false positivity. In few cases, PET correctly detects residual PSMA expression post-radiotherapy, originating however from treated, benign tissue or potentially indolent tumor remnants.

Trial Registration Number: ClinicalTrials.gov Identifiers: NCT02940262 and NCT03353740.
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http://dx.doi.org/10.1007/s00259-020-04945-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835157PMC
February 2021

Volumetric PET Response Assessment Outperforms Conventional Criteria in Patients Receiving High-Dose Pembrolizumab for Malignant Mesothelioma.

J Nucl Med 2021 02 12;62(2):191-194. Epub 2020 Jun 12.

Department of Medical Oncology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.

Fixed-dose pembrolizumab (200 mg absolute, day 1, every 3 wk) for the treatment of malignant pleural mesothelioma did not result in survival benefit in the phase 3 PROMISE-meso trial compared with second-line chemotherapy. Because of lack of validated imaging response criteria, responder subgroups with potential survival benefit have not yet been identified. Here, we administered high-dose pembrolizumab (10 mg/kg, day 1, every 2 wk) considering the KEYNOTE-028 trial and assessed the prognostic value of PET metabolic response in patients with chemotherapy-resistant malignant mesothelioma of the pleura or peritoneum. Data from 27 patients with baseline and follow-up F-FDG PET/CT imaging were retrospectively analyzed. RECIST, version 1.1; modified RECIST; and PERCIST using both tumor lesion metabolic activity in a 1 cm spheric region of interest of up to 5 target lesions (PERCIST) and metabolic tumor volume PERCIST (PERCIST) were applied separately to categorize responders in CT and PET imaging studies. Progression-free survival (PFS) and overall survival (OS) were compared between responders and nonresponders using Kaplan-Meier and log-rank analyses. Programmed cell death protein 1 ligand expression status was assessed, and its association with outcome was investigated. Twenty-seven patients had F-FDG PET/CT imaging at baseline and after at least 4 cycles pembrolizumab. Median PFS and OS were 3.4 and 15.1 mo, respectively. Response rates were 7%, 7%, 30%, and 30% based on RECIST, modified RECIST, PERCIST, and PERCIST response criteria, respectively. Response according to PERCIST predicted prolonged OS or PFS ( < 0.01), whereas all other imaging criteria and programmed cell death protein 1 ligand expression did not. F-FDG PET metabolic volume response predicts survival in patients with malignant mesothelioma receiving high-dose pembrolizumab. These results should prompt inclusion of PET response assessment in future phase 3 clinical trials.
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http://dx.doi.org/10.2967/jnumed.120.245803DOI Listing
February 2021

Efficacy and Safety of Lu-labeled Prostate-specific Membrane Antigen Radionuclide Treatment in Patients with Diffuse Bone Marrow Involvement: A Multicenter Retrospective Study.

Eur Urol 2020 08 10;78(2):148-154. Epub 2020 Jun 10.

Department of Molecular Imaging and Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

The Lu-labeled prostate-specific membrane antigen (LuPSMA) radionuclide therapy for metastatic castration-resistant prostate cancer is under investigation in a phase III trial (VISION: NCT03511664). However, patients with diffuse bone involvement, diagnosed with a "superscan" by bone scintigraphy at baseline, were excluded due to a lack of efficacy and safety data. We therefore aimed to investigate the feasibility of LuPSMA in patients with diffuse bone marrow involvement on baseline PSMA-targeted positron emission tomography. The primary end points were prostate-specific antigen (PSA) response (Prostate Cancer Working Group 3 [PCWG3]), hematologic safety profile (Common Terminology Criteria for Common Adverse Events [CTCAE]), and overall survival. Secondary end points of quality of life (assessed with Brief Pain Inventory-Short Form questionnaires) and radiologic response (Response Evaluation Criteria in Solid Tumors [RECIST]) were assessed. Through retrospective screening of databases, we identified 43 eligible patients across four centers worldwide who received 154 cycles of LuPSMA under clinical trials or compassionate access programs. Median baseline PSA was 1000 (interquartile range 431-2151) ng/ml. PSA decline of at least 50% at 12 wk was achieved in 22 (58%) patients, while median time to pain progression was 8.3 (95% confidence interval [CI] 4.1-12.6) mo. Median overall survival was 11.6 (95% CI 8.8-14.3) mo. Objective response in nodal or visceral disease was reported in seven (39%) of 18 patients with RECIST measurable disease. Grade 3 anemia, thrombocytopenia, and neutropenia occurred in nine (22%), seven (17%), and three (8%) patients, respectively. Grade 4 thrombocytopenia was noticed in three (8%) patients. In conclusion, patients with diffuse bone marrow involvement demonstrated similar LuPSMA efficacy and safety to phase II evidence. Acceptable safety outcomes do not support exclusion of patients with a superscan from future LuPSMA treatment protocols. PATIENT SUMMARY: In this report, we investigated the feasibility of prostate-specific membrane antigen (PSMA)-directed radionuclide treatment in patients with metastatic castration-resistant prostate cancer and diffuse bone involvement. We found that, despite a high load of bone metastases, PSMA-targeted therapy remains efficacious and safe when compared with the current phase II trial results.
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http://dx.doi.org/10.1016/j.eururo.2020.05.004DOI Listing
August 2020

PSMA-Ligand PET for Early Castration-Resistant Prostate Cancer: A Retrospective Single-Center Study.

J Nucl Med 2021 01 22;62(1):88-91. Epub 2020 May 22.

Department of Nuclear Medicine, University of Duisburg-Essen, and German Cancer Consortium-University Hospital Essen, Essen, Germany

The low detection rate of conventional imaging and unspecific fluctuations in prostate-specific antigen can hamper early diagnosis of castration-resistant prostate cancer (CRPC). We thus assessed the value of prostate-specific membrane antigen (PSMA) PET/CT in the detection of early CRPC (prostate-specific antigen ≤ 3 ng/mL). We identified 55 patients with early CRPC from our institutional database. PSMA PET/CT and its CT component were interpreted independently by 3 masked readers. The primary endpoint was the per-patient detection rate; secondary endpoints were interobserver agreement and predictors of PET positivity. PSMA PET/CT was positive in 41 of 55 (75%) patients. Sixteen of 55 (29%) patients had local disease only, and 25 of 55 (45%) had M1 disease. Overall, PSMA PET/CT interobserver agreement was substantial by Landis and Koch criteria (Fleiss κ = 0.77). PSMA PET/CT localized prostate cancer lesions in 75% of patients and M1 disease in 45%. Detection of early CRPC facilitates disease-delaying therapies for local or oligometastatic disease. PSMA PET/CT is of value in early CRPC and should be included in the CRPC entry criteria of the European Association of Urology and Prostate Cancer Working Group 3.
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http://dx.doi.org/10.2967/jnumed.120.245456DOI Listing
January 2021

Impact of Ga-PSMA-11 PET on the Management of Recurrent Prostate Cancer in a Prospective Single-Arm Clinical Trial.

J Nucl Med 2020 12 1;61(12):1793-1799. Epub 2020 May 1.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California

Prostate-specific membrane antigen (PSMA) ligand PET induces management changes in patients with prostate cancer. We aim to better characterize the impact of Ga-PSMA-11 PET (Ga-PSMA PET) on management of recurrent prostate cancer in a large prospective cohort. We report management changes after Ga-PSMA PET, a secondary endpoint of a prospective multicenter trial in men with biochemical recurrence of prostate cancer. Pre-PET (Q1), post-PET (Q2), and posttreatment (Q3) questionnaires were sent to referring physicians recording site of recurrence and intended (Q1 to Q2 change) and implemented (Q3) therapeutic and diagnostic management. Q1 and Q2 response was collected for 382 of 635 patients (60%, intended cohort), and Q1, Q2, and Q3 response was collected for 206 patients (32%, implemented cohort). An intended management change occurred in 260 of 382 (68%) patients. The intended change was considered major in 176 of 382 (46%) patients. Major changes occurred most often for patients with prostate-specific antigen of 0.5 to less than 2.0 ng/mL (81/147, 55%). By analysis of stage groups, management change was consistent with PET disease location, that is, a majority of major changes toward active surveillance (47%) for unknown disease site (103/382, 27%), toward local or focal therapy (56%) for locoregional disease (126/382, 33%), and toward systemic therapy (69% M1a; 43% M1b/c) for metastatic disease (153/382, 40%). According to Q3 responses, the intended management was implemented in 160 of 206 (78%) patients. In total, 150 intended diagnostic tests, mostly CT ( = 43, 29%) and bone scans or F-NaF PET ( = 52, 35%), were prevented by Ga-PSMA PET; 73 tests, mostly biopsies ( = 44, 60%) as requested by the study protocol, were triggered. According to referring physicians, sites of recurrence were clarified by Ga-PSMA PET, and disease localization translated into management changes in more than half of patients with biochemical recurrence of prostate cancer.
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http://dx.doi.org/10.2967/jnumed.120.242180DOI Listing
December 2020

In vivo biodistribution of calcium phosphate nanoparticles after intravascular, intramuscular, intratumoral, and soft tissue administration in mice investigated by small animal PET/CT.

Acta Biomater 2020 06 4;109:244-253. Epub 2020 Apr 4.

Inorganic Chemistry and Centre for Nanointegration Duisburg-Essen (CeNIDE), University of Duisburg-Essen, Essen, Germany. Electronic address:

Calcium phosphate nanoparticles were covalently surface-functionalized with the ligand DOTA and loaded with the radioisotope Ga. The biodistribution of such Ga-labelled nanoparticles was followed in vivo in mice by positron emission tomography in combination with computer tomography (PET-CT). The biodistribution of Ga-labelled nanoparticles was compared for different application routes: intravenous, intramuscular, intratumoral, and into soft tissue. The particle distribution was measured in vivo by PET-CT after 5 min, 15 min, 30 min, 1 h, 2 h, and 4 h, and ex vivo after 5 h. After intravenous injection (tail vein), the nanoparticles rapidly entered the lungs with later redistribution into liver and spleen. The nanoparticles remained mostly at the injection site following intramuscular, intratumoral, or soft tissue application, with less than 10 percent being mobilized into the blood stream. STATEMENT OF SIGNIFICANCE: The in vivo biodistribution of DOTA-terminated calcium phosphate nanoparticles was followed by PET/CT. To our knowledge, this is the first study of this kind. Four different application routes of clinical relevance were pursued: Intravascular, intramuscular, intratumoral, and into soft tissue. Given the high importance of calcium phosphate as biomaterial and for nanoparticular drug delivery and immunization, this is most important to assess the biofate of calcium phosphate nanoparticles for therapeutic application and also judge biodistribution of nanoscopic calcium phosphate ceramics, including debris from endoprostheses and related implants.
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http://dx.doi.org/10.1016/j.actbio.2020.03.031DOI Listing
June 2020

Imaging inflammation after myocardial infarction: implications for prognosis and therapeutic guidance.

Q J Nucl Med Mol Imaging 2020 Mar 18;64(1):35-50. Epub 2020 Feb 18.

Department of Nuclear Medicine, University Hospital Essen, Essen, Germany -

Inflammation after myocardial infarction (MI) has been in the focus of cardiovascular research for several years as it influences the remodeling process of the ischemic heart and thereby critically determines the clinical outcome of the patient. Today, it is well appreciated that inflammation is a crucial necessity for the initiation of the natural wound healing process; however, excessive inflammation can have detrimental effects and might result in adverse ventricular remodeling which is associated with an increased risk of heart failure. Newly emerged imaging techniques facilitate the non-invasive assessment of immune cell infiltration into the ischemic myocardium and can provide greater insight into the underlying complex and dynamic repair mechanisms. Molecular imaging of inflammation in the context of MI may help with stratification of patients at high risk of adverse ventricular remodeling post-MI which may be of diagnostic, therapeutic, and prognostic value. Novel radiopharmaceuticals may additionally provide a way to combine patient monitoring and therapy. In spite of great advances in recent years in the field of imaging sciences, clinicians still need to overcome some obstacles to a wider implementation of inflammation imaging post-MI. This review focuses on inflammation as a molecular imaging target and its potential implication in prognosis and therapeutic guidance.
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http://dx.doi.org/10.23736/S1824-4785.20.03232-XDOI Listing
March 2020

Intraoperative Ga-PSMA Cerenkov Luminescence Imaging for Surgical Margins in Radical Prostatectomy: A Feasibility Study.

J Nucl Med 2020 10 14;61(10):1500-1506. Epub 2020 Feb 14.

Department of Urology, University Hospital Essen, Essen, Germany.

Our objective was to assess the feasibility and accuracy of Cerenkov luminescence imaging (CLI) for assessment of surgical margins intraoperatively during radical prostatectomy. A single-center feasibility study included 10 patients with high-risk primary prostate cancer (PC). Ga-prostate-specific membrane antigen (PSMA) PET/CT scans were performed followed by radical prostatectomy and intraoperative CLI of the excised prostate. In addition to imaging the intact prostate, in the first 2 patients the prostate gland was incised and imaged with CLI to visualize the primary tumor. We compared the tumor margin status on CLI to postoperative histopathology. Measured CLI intensities were determined as tumor-to-background ratio. Tumor cells were successfully detected on the incised prostate CLI images as confirmed by histopathology. Three of 10 men had histopathologically positive surgical margins (PSMs), and 2 of 3 PSMs were accurately detected on CLI. Overall, 25 (72%) of 35 regions of interest proved to visualize a tumor signal according to standard histopathology. The median tumor radiance in these areas was 11,301 photons/s/cm/sr (range, 3,328-25,428 photons/s/cm/sr), and median tumor-to-background ratio was 4.2 (range, 2.1-11.6). False-positive signals were seen mainly at the prostate base, with PC cells overlaid by benign tissue. PSMA immunohistochemistry revealed strong PSMA staining of benign gland tissue, which impacts measured activities. This feasibility showed that Ga-PSMA CLI is a new intraoperative imaging technique capable of imaging the entire specimen's surface to detect PC tissue at the resection margin. Further optimization of the CLI protocol, or the use of lower-energy imaging tracers such as F-PSMA, is required to reduce false-positives. A larger study will be performed to assess diagnostic performance.
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http://dx.doi.org/10.2967/jnumed.119.240424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539648PMC
October 2020

18F-FDG-PET/MRI in the diagnostic work-up of limbic encephalitis.

PLoS One 2020 17;15(1):e0227906. Epub 2020 Jan 17.

Institute for Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.

Introduction: Limbic encephalitis (LE) is an immune-related, sometimes paraneoplastic process of the central nervous system. Initial diagnosis and treatment are based on the clinical presentation as well as antibody profiles and MRI. This study investigated the diagnostic value of integrated 18F-FDG-PET/MRI in the diagnostic work-up of patients with LE for a cerebral and whole-body imaging concept.

Material And Methods: Twenty patients with suspected LE were enrolled in this prospective study. All patients underwent a dedicated PET/MRI protocol of the brain as well as the whole-body. Two neuroradiologists, one body radiologist and one nuclear medicine physician performed blinded consensus readings of each corresponding MRI and PET/MRI dataset of the brain and whole-body. Diagnostic confidence was evaluated on a Likert scale.

Results: Based on integrated PET/MRI 19 / 20 patients were found to show morphologic and / or metabolic changes indicative of LE, whereas sole MRI enabled correct identification in 16 / 20 patients. Three patients with negative MRI showed metabolic changes of the limbic system or extra-limbic regions, shifting the diagnosis from (negative) MRI to positive for LE in PET/MRI. Whole-body staging revealed suspected lesions in 2/20 patients, identified by MRI and PET, one confirmed as malignant and one false positive. Diagnostic confidence for cerebral and whole-body imaging reached higher scores for PET/MRI (cerebral: 2.7 and whole body: 4.8) compared to MRI alone (cerebral: 2.4 and whole body: 4.5).

Conclusion: LE diagnosis remains challenging for imaging as it shows only subtle imaging findings in most patients. Nevertheless, based on the simultaneous and combined analysis of morphologic and metabolic data, integrated PET/MRI may enable a dual platform for improved diagnostic confidence and overall detection of LE as well as whole-body imaging for exclusion of paraneoplastic LE.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0227906PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6968877PMC
April 2020

Impact of Ga-PSMA-11 PET/CT on Staging and Management of Prostate Cancer Patients in Various Clinical Settings: A Prospective Single-Center Study.

J Nucl Med 2020 08 10;61(8):1153-1160. Epub 2020 Jan 10.

Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, California.

The impact of prostate-specific membrane antigen (PSMA) PET/CT on management of prostate cancer (PCa) patients with biochemical recurrence (BCR) is well established. However, whether and how PSMA PET/CT affects the management of patients undergoing scans for other clinical indications remains unknown. The goal of this study was to determine the impact of Ga-PSMA-11 PET/CT on initial and subsequent management decisions in a cohort of PCa patients referred for various indications (i.e., a basket trial) excluding the 2 main classic indications: BCR and presurgical staging. This was a prospective study of 197 patients that aimed to determine the impact of Ga-PSMA-11 PET/CT on PCa stage and management. The indications for PSMA PET/CT were initial staging of nonsurgical candidates (30 patients) and restaging after definitive treatment (167 patients). The restaging cohort comprised patients restaged with known advanced metastatic disease ( = 103), after androgen deprivation therapy only ( = 16), after surgery and with serum prostate-specific antigen levels lower than 0.2 ng/mL ( = 13), after radiation therapy and not meeting the Phoenix criteria ( = 22), and after other primary local treatments (i.e., high-intensity focused ultrasound, focal laser ablation, cryoablation, hyperthermia, or irreversible electroporation) ( = 13). Patients with BCR and candidates for curative surgery were excluded. Impact on management was assessed using pre- and post-PET questionnaires completed by referring physicians, electronic chart review, or patient telephone calls. PSMA PET/CT changed the disease stage in 135 of 197 (69%) patients (upstaging in 38%, downstaging in 30%, and no change in stage in 32%). Management was affected in 104 of 182 (57%) patients. Specifically, PSMA PET/CT impacted the management of patients who were restaged after radiation therapy without meeting the Phoenix criteria for BCR, after other definitive local treatments, and with advanced metastatic disease in 13 of 18 (72%), 8 of 12 (67%), and 59 of 96 (61%), respectively. PSMA PET/CT has a profound impact on stage and management of PCa patients outside the 2 main classic indications (BCR and presurgical staging) across all examined clinical scenarios.
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http://dx.doi.org/10.2967/jnumed.119.237602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413232PMC
August 2020

What is the best PET target for early biochemical recurrence of prostate cancer?-Authors' reply.

Lancet Oncol 2019 11;20(11):e609-e610

Ahmanson Translational Theranostics Division, Department of Medical and Molecular Pharmacology, University of California Los Angeles, CA 900095-7370, USA; Institute of Urologic Oncology, University of California Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California Los Angeles, CA, USA.

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http://dx.doi.org/10.1016/S1470-2045(19)30654-0DOI Listing
November 2019

Prostate-Specific Membrane Antigen Ligand Positron Emission Tomography in Men with Nonmetastatic Castration-Resistant Prostate Cancer.

Clin Cancer Res 2019 12 11;25(24):7448-7454. Epub 2019 Sep 11.

University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany.

Purpose: Systemic androgen-signaling inhibition added to ongoing androgen-deprivation therapy (ADT) improved clinical outcomes in patients with nonmetastatic castration-resistant prostate cancer without detectable metastases by conventional imaging (nmCRPC). Prostate-specific membrane antigen ligand positron emission tomography (PSMA-PET) detects prostate cancer with superior sensitivity to conventional imaging, but its performance in nmCRPC remains largely unknown. We characterized cancer burden in high-risk patients with nmCRPC using PSMA-PET.

Experimental Design: We retrospectively included 200 patients with nmCRPC, prostate-specific antigen (PSA) >2 ng/mL, and high risk for metastatic disease [PSA doubling time (PSADT) of ≤10 months and/or Gleason score of ≥8] from six high-volume PET centers. We centrally reviewed PSMA-PET detection rate for pelvic disease and distant metastases (M1). We further evaluated SPARTAN patients stratified by risk factors for PSMA-PET-detected M1 disease.

Results: PSMA-PET was positive in 196 of 200 patients. Overall, 44% had pelvic diseases, including 24% with local prostate bed recurrence, and 55% had M1 disease despite negative conventional imaging. Interobserver agreement was very high (κ: 0.81-0.91). PSA ≥ 5.5 ng/mL, locoregional nodal involvement determined by pathology (pN1), prior primary radiation, and prior salvage radiotherapy independently predicted M1 disease (all < 0.05).

Conclusions: PSMA-PET detected any disease in nearly all patients and M1 disease in 55% of patients previously diagnosed with nmCRPC, including subgroups with PSADT of ≤10 months and Gleason score of ≥8. The value of PSMA-PET imaging for treatment guidance should be tested in future studies.
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http://dx.doi.org/10.1158/1078-0432.CCR-19-1050DOI Listing
December 2019

F-fluciclovine PET-CT and Ga-PSMA-11 PET-CT in patients with early biochemical recurrence after prostatectomy: a prospective, single-centre, single-arm, comparative imaging trial.

Lancet Oncol 2019 09 30;20(9):1286-1294. Epub 2019 Jul 30.

Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA; Institute of Urologic Oncology, University of California Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA.

Background: National Comprehensive Cancer Network guidelines consider F-fluciclovine PET-CT for prostate cancer biochemical recurrence localisation after radical prostatectomy, whereas European Association of Urology guidelines recommend prostate-specific membrane antigen (PSMA) PET-CT. To the best of our knowledge, no prospective head-to-head comparison between these tests has been done so far. The aim of this study was to compare prospectively paired F-fluciclovine and PSMA PET-CT scans for localising biochemical recurrence of prostate cancer after radical prostatectomy in patients with low prostate-specific antigen (PSA) concentrations (<2·0 ng/mL).

Methods: This was a prospective, single-centre, open-label, single-arm comparative study done at University of California Los Angeles (Los Angeles, CA, USA). Patients older than 18 years of age with prostate cancer biochemical recurrence after radical prostatectomy and PSA levels ranging from 0·2 to 2·0 ng/mL without any prior salvage therapy and with a Karnofsky performance status of at least 50 were eligible. Patients underwent F-fluciclovine (reference test) and PSMA (index test) PET-CT scans within 15 days. Detection rate of biochemical recurrence at the patient level and by anatomical region was the primary endpoint. A statistical power analysis demonstrated that a sample size of 50 patients was needed to show a 22% difference in detection rates in favour of PSMA (test for superiority). Each PET scan was interpreted by three independent masked readers and a consensus majority interpretation was generated (two vs one) to determine positive findings. This study is registered with ClinicalTrials.gov, number NCT02940262, and is complete.

Findings: Between Feb 26, 2018, and Sept 20, 2018, 143 patients were screened for eligibility, of whom 50 patients were enrolled into the study. Median follow-up was 8 months (IQR 7-9). The primary endpoint was met; detection rates were significantly lower with F-fluciclovine PET-CT (13 [26%; 95% CI 15-40] of 50) than with PSMA PET-CT (28 [56%; 41-70] of 50), with an odds ratio (OR) of 4·8 (95% CI 1·6-19·2; p=0·0026) at the patient level; in the subanalysis of the pelvic nodes region (four [8%; 2-19] with F-fluciclovine vs 15 [30%; 18-45] with PSMA PET-CT; OR 12·0 [1·8-513·0], p=0·0034); and in the subanalysis of any extrapelvic lesions (none [0%; 0-6] vs eight [16%; 7-29]; OR non-estimable [95% CI non-estimable], p=0·0078).

Interpretation: With higher detection rates, PSMA should be the PET tracer of choice when PET-CT imaging is considered for subsequent treatment management decisions in patients with prostate cancer and biochemical recurrence after radical prostatectomy and low PSA concentrations (≤2·0 ng/mL). Further research is needed to investigate whether higher detection rates translate into improved oncological outcomes.

Funding: None.
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http://dx.doi.org/10.1016/S1470-2045(19)30415-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469487PMC
September 2019

Can the Injected Dose Be Reduced in Ga-PSMA-11 PET/CT While Maintaining High Image Quality for Lesion Detection?

J Nucl Med 2020 02 19;61(2):189-193. Epub 2019 Jul 19.

Department of Nuclear Medicine, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.

Our purpose was to define a clinically useful lower limit of injected dose for Ga-prostate-specific membrane antigen (PSMA)-11 PET/CT imaging of prostate cancer. Ga-PSMA-11 PET/CT was performed on 11 patients. PET was acquired in list mode and reconstructed using a 3-min full acquisition, a 2-min acquisition, and a 1-min acquisition to generate images obtained with three thirds (standard dose), two thirds (low dose), and one third (very low dose) of the injected dose, respectively. Overall image quality (5-point scale) was assessed, and the detectability of PSMA-positive lesions was determined by 3 readers and compared with the reference standard. Image quality declined with decreasing dose (mean score of 4.1 ± 0.4 for the standard dose, 3.4 ± 0.7 for the low dose, and 1.9 ± 0.4 for the very low dose; all < 0.05). Readers 1, 2, and 3 correctly identified the lesions ( = 21) at a rate of 100%, 100%, and 95% with the standard dose; 95%, 81%, and 90% with the low dose; and 71%, 76%, and 59% with the very low dose, respectively. Ga-PSMA-11 dose reduction is not feasible without a negative impact on image quality and lesion detectability.
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http://dx.doi.org/10.2967/jnumed.119.227207DOI Listing
February 2020

Molecular Imaging for Primary Staging of Prostate Cancer.

Semin Nucl Med 2019 07 20;49(4):271-279. Epub 2019 Mar 20.

Department of Nuclear Medicine, University Hospital Essen, University of Duisburg-Essen, Germany.

According to SEER Cancer Statistics Review there are around 165,000 new prostate cancer cases estimated in 2018 accounting for 9.5% of all newly diagnosed cancers. Accurate staging of primary prostate cancer is important for therapy selection (local vs systemic). Recent developments in molecular imaging may significantly impact staging procedures and management. Accordingly, this article addresses the current clinical standard, discusses the areas of unmet clinical need for imaging and then summarizes the most commonlyused molecular imaging probes. Finally, the authors dare an outlook to the short-term future role of molecular imaging in primary staging of prostate cancer.
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http://dx.doi.org/10.1053/j.semnuclmed.2019.02.004DOI Listing
July 2019

Improving Ga-PSMA PET/MRI of the Prostate with Unrenormalized Absolute Scatter Correction.

J Nucl Med 2019 11 12;60(11):1642-1648. Epub 2019 Apr 12.

High-Field and Hybrid MR Imaging, University Hospital Essen, University Duisburg-Essen, Essen, Germany.

A limitation of using Ga-labeled prostate-specific membrane antigen (Ga-PSMA) for detection and staging of prostate cancer is a frequently observed halo artifact around the urinary bladder caused by inaccurate scatter correction (SC) of PET data. The aim of this study was to investigate the impact of unrenormalized absolute SC on Ga-PSMA PET quantification in PET/MRI of the prostate in 100 patients. The PET data of 100 patients were reconstructed twice using standard SC and improved unrenormalized SC. The visual presence of the halo artifact was rated in each PET data reconstruction using 5 grades (0, no halo artifact; 4, severe halo artifact). The number of visible lesions in the pelvis was recorded. SUV and SUV were measured in the lesions, in the bladder, in the gluteus maximus, and within the halo margin. Furthermore, the signal-to-noise-ratio and image noise were measured in all PET data. Relative differences between standard and unrenormalized SC were calculated. With standard SC, the average grade in the presence of the halo artifact was 2 (moderate halo artifact), whereas for unrenormalized SC, the average grade was 0.9 (slight halo artifact). The same number of congruent lesions ( = 74) was detected for both PET data reconstructions. Relative changes in PET signal-to-noise-ratio and image noise were not statistically significant ( > 0.05). The mean (±SD) increase in SUV using unrenormalized SC was 23.0% ± 9.2% in the gluteus maximus, 7.1% ± 4.5% in the bladder, 325.4% ± 748.5% in the halo margin, and 12.4% ± 16.8% in all 74 detected lesions. The mean increase using unrenormalized SC in SUV was 17.5% for lesions inside the halo margin (38 lesions) and 6.9% for lesions outside the halo margin (36 lesions). For PET/MRI of prostate cancer using Ga-PSMA, a proper SC is important to ensure the best possible diagnostic quality and PET quantification. Unrenormalized absolute SC significantly reduces the halo artifact around the bladder and improves PET/MRI of the prostate.
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http://dx.doi.org/10.2967/jnumed.118.224139DOI Listing
November 2019

Assessment of 68Ga-PSMA-11 PET Accuracy in Localizing Recurrent Prostate Cancer: A Prospective Single-Arm Clinical Trial.

JAMA Oncol 2019 Jun;5(6):856-863

Departments of Radiology and Biomedical Imaging and Pharmaceutical Chemistry, University of California San Francisco, San Francisco.

Importance: In retrospective studies, 68Ga-PSMA-11 positron emission tomographic (PET) imaging improves detection of biochemically recurrent prostate cancer compared with conventional imaging.

Objective: To assess 68Ga-PSMA-11 PET accuracy in a prospective multicenter trial.

Design, Setting, And Participants: In this single-arm prospective trial conducted at University of California, San Francisco and University of California, Los Angeles, 635 patients with biochemically recurrent prostate cancer after prostatectomy (n = 262, 41%), radiation therapy (n = 169, 27%), or both (n = 204, 32%) underwent 68Ga-PSMA-11 PET. Presence of prostate cancer was recorded by 3 blinded readers on a per-patient and per-region base. Lesions were validated by histopathologic analysis and a composite reference standard.

Main Outcomes And Measures: Endpoints were positive predictive value (PPV), detection rate, interreader reproducibility, and safety.

Results: A total of 635 men were enrolled with a median age of 69 years (range, 44-95 years). On a per-patient basis, PPV was 0.84 (95% CI, 0.75-0.90) by histopathologic validation (primary endpoint, n = 87) and 0.92 (95% CI, 0.88-0.95) by the composite reference standard (n = 217). 68Ga-PSMA-11 PET localized recurrent prostate cancer in 475 of 635 (75%) patients; detection rates significantly increased with prostate-specific antigen (PSA): 38% for <0.5 ng/mL (n = 136), 57% for 0.5 to <1.0 ng/mL (n = 79), 84% for 1.0 to <2.0 ng/mL (n = 89), 86% for 2.0 to <5.0 ng/mL (n = 158), and 97% for ≥5.0 ng/mL (n = 173, P < .001). Interreader reproducibility was substantial (Fleiss κ, 0.65-0.78). There were no serious adverse events associated with 68Ga-PSMA-11 administration. PET-directed focal therapy alone led to a PSA drop of 50% or more in 31 of 39 (80%) patients.

Conclusions And Relevance: Using blinded reads and independent lesion validation, we establish high PPV for 68Ga-PSMA-11 PET, detection rate and interreader agreement for localization of recurrent prostate cancer.

Trial Registration: ClinicalTrials.gov identifiers: NCT02940262 and NCT03353740.
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http://dx.doi.org/10.1001/jamaoncol.2019.0096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6567829PMC
June 2019

Correction to: Randomized prospective phase III trial of 68Ga-PSMA-11 PET/CT molecular imaging for prostate cancer salvage radiotherapy planning [PSMA-SRT].

BMC Cancer 2019 01 21;19(1):97. Epub 2019 Jan 21.

Department of Radiation Oncology, University of California, Los Angeles, USA.

Following publication of the original article [1], we have been notified that one of the author names was listed incorrectly.
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http://dx.doi.org/10.1186/s12885-019-5297-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341574PMC
January 2019

Randomized prospective phase III trial of Ga-PSMA-11 PET/CT molecular imaging for prostate cancer salvage radiotherapy planning [PSMA-SRT].

BMC Cancer 2019 Jan 7;19(1):18. Epub 2019 Jan 7.

Department of Radiation Oncology, University of California, Los Angeles, USA.

Background: Salvage radiotherapy (SRT) for prostate cancer (PCa) recurrence after prostatectomy offers long-term biochemical control in about 50-60% of patients. SRT is commonly initiated in patients with serum PSA levels < 1 ng/mL, a threshold at which standard-of-care imaging is insensitive for detecting recurrence. As such, SRT target volumes are usually drawn in the absence of radiographically visible disease. Ga-PSMA-11 (PSMA) PET/CT molecular imaging is highly sensitive and may offer anatomic localization of PCa biochemical recurrence. However, it is unclear if incorporation of PSMA PET/CT imaging into the planning of SRT could improve its likelihood of success. The purpose of this trial is to evaluate the success rate of SRT for recurrence of PCa after prostatectomy with and without planning based on PSMA PET/CT.

Methods: We will randomize 193 patients to proceed with standard SRT (control arm 1, n = 90) or undergo a PSMA PET/CT scan (free of charge for patients) prior to SRT planning (investigational arm 2, n = 103). The primary endpoint is the success rate of SRT measured as biochemical progression-free survival (BPFS) after initiation of SRT. Biochemical progression is defined by PSA ≥ 0.2 ng/mL and rising. The randomization ratio of 1:1.13 is based on the assumption that approximately 13% of subjects randomized to Arm 2 will not be treated with SRT because of PSMA-positive extra-pelvic metastases. These patients will not be included in the primary endpoint analysis but will still be followed. The choice of treating the prostate bed alone vs prostate bed and pelvic lymph nodes, with or without androgen deprivation therapy (ADT), is selected by the treating radiation oncologist. The radiation oncologist may change the radiation plan depending on the findings of the PSMA PET/CT scan. Any other imaging is allowed for SRT planning in both arms if done per routine care. Patients will be followed until either one of the following conditions occur: 5 years after the date of initiation of randomization, biochemical progression, diagnosis of metastatic disease, initiation of any additional salvage therapy, death.

Discussion: This is the first randomized phase 3 prospective trial designed to determine whether PSMA PET/CT molecular imaging can improve outcomes in patients with PCa early BCR following radical prostatectomy.

Acronym: PSMA-SRT Phase 3 trial.

Clinical Trial Registration: ■ IND#130649 ◦ Submission: 04.26.2016 ◦ Safe-to-proceed letter issued by FDA: 05.25.2016 ■ UCLA IRB #18-000484, ■ First submission: 3.27.2018 ■ Date of approval: 5.31.2018 ■ UCLA JCCC Short Title NUC MED 18-000484 ■ NCI Trial Identifier NCI-2018-01518 ■ ClinicalTrials.gov Identifier NCT03582774 ■ First Submitted: 06.19.2018 ■ First Submitted that Met QC Criteria: 06.27.2018 ■ First Posted: 07.11.2018 ■ Last Update Submitted that Met QC Criteria: 07.17.2018 ■ Last Update Posted: 07.19.2018 TRIAL STATUS: Current Trial Status Active as of 08/13/2018 Trial Start Date 09/01/2018-Actual Primary Completion Date 09/01/2023-Anticipated Trial Completion Date 09/01/2024-Anticipated.
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http://dx.doi.org/10.1186/s12885-018-5200-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322287PMC
January 2019