Publications by authors named "Wim J G Oyen"

390 Publications

[F]FDG-PET/CT to prevent futile surgery in indeterminate thyroid nodules: a blinded, randomised controlled multicentre trial.

Eur J Nucl Med Mol Imaging 2022 Jan 4. Epub 2022 Jan 4.

Department of Radiology, Section of Nuclear Medicine, Leiden University Medical Center, Leiden, the Netherlands.

Purpose: To assess the impact of an [F]FDG-PET/CT-driven diagnostic workup to rule out malignancy, avoid futile diagnostic surgeries, and improve patient outcomes in thyroid nodules with indeterminate cytology.

Methods: In this double-blinded, randomised controlled multicentre trial, 132 adult euthyroid patients with scheduled diagnostic surgery for a Bethesda III or IV thyroid nodule underwent [F]FDG-PET/CT and were randomised to an [F]FDG-PET/CT-driven or diagnostic surgery group. In the [F]FDG-PET/CT-driven group, management was based on the [F]FDG-PET/CT result: when the index nodule was visually [F]FDG-positive, diagnostic surgery was advised; when [F]FDG-negative, active surveillance was recommended. The nodule was presumed benign when it remained unchanged on ultrasound surveillance. In the diagnostic surgery group, all patients were advised to proceed to the scheduled surgery, according to current guidelines. The primary outcome was the fraction of unbeneficial patient management in one year, i.e., diagnostic surgery for benign nodules and active surveillance for malignant/borderline nodules. Intention-to-treat analysis was performed. Subgroup analyses were performed for non-Hürthle cell and Hürthle cell nodules.

Results: Patient management was unbeneficial in 42% (38/91 [95% confidence interval [CI], 32-53%]) of patients in the [F]FDG-PET/CT-driven group, as compared to 83% (34/41 [95% CI, 68-93%]) in the diagnostic surgery group (p < 0.001). [F]FDG-PET/CT-driven management avoided 40% (25/63 [95% CI, 28-53%]) diagnostic surgeries for benign nodules: 48% (23/48 [95% CI, 33-63%]) in non-Hürthle cell and 13% (2/15 [95% CI, 2-40%]) in Hürthle cell nodules (p = 0.02). No malignant or borderline tumours were observed in patients under surveillance. Sensitivity, specificity, negative and positive predictive value, and benign call rate (95% CI) of [F]FDG-PET/CT were 94.1% (80.3-99.3%), 39.8% (30.0-50.2%), 95.1% (83.5-99.4%), 35.2% (25.4-45.9%), and 31.1% (23.3-39.7%), respectively.

Conclusion: An [F]FDG-PET/CT-driven diagnostic workup of indeterminate thyroid nodules leads to practice changing management, accurately and oncologically safely reducing futile surgeries by 40%. For optimal therapeutic yield, application should be limited to non-Hürthle cell nodules.

Trial Registration Number: This trial is registered with ClinicalTrials.gov: NCT02208544 (5 August 2014), https://clinicaltrials.gov/ct2/show/NCT02208544 .
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http://dx.doi.org/10.1007/s00259-021-05627-2DOI Listing
January 2022

18F-FDG PET-CT scanning in rheumatoid arthritis patients tapering TNFi: reliability, validity and predictive value.

Rheumatology (Oxford) 2021 Nov 13. Epub 2021 Nov 13.

Department of Rheumatology, Sint Maartenskliniek, Nijmegen, The Netherlands.

Objectives: To investigate the reliability and validity of 18F-FDG PET-CT scanning (FDG-PET) in rheumatoid arthritis (RA) patients with low disease activity tapering tumor necrosis factor inhibitors (TNFi) and its' predictive value for successful tapering or discontinuation.

Methods: Patients in the tapering arm of the DRESS study, a randomized controlled trial on TNFi tapering in RA, underwent FDG-PET before tapering (baseline) and after maximal tapering. 48 joints per scan were scored: 1) visually (FDG-avid joint (FAJ) y/n), 2) quantitatively (maximal and mean standardized uptake values (SUVmax and SUVmean)). Interobserver agreement was calculated in 10 patients at baseline. Quantitative and visual FDG-PET scores were investigated for: 1) (multilevel) association with clinical parameters both on joint and patient level and 2) predictive value at baseline and change between baseline and maximal tapering (delta) for successful tapering and discontinuation at 18 months.

Results: 79 patients underwent FDG-PET. For performance of identification of FAJs on PET, Cohen's kappa was 0.49 (0.35-0.63). For SUVmax and SUVmean, ICCs were 0.80 (0.77-0.83) and 0.96 (0.9-1.0), respectively. On joint level, swelling was significantly associated with SUVmax and SUVmean (B coefficients with 95%CI 1.0 (0.73-1.35) and 0.2 (0.08-0.32) respectively). On patient level only correlation with acute phase reactants was found. FDG-PET scores were not predictive for successful tapering or discontinuation.

Conclusions: Quantitative FDG-PET arthritis scoring in RA patients with low disease activity is reliable and has some construct validity. However, no predictive values were found for FDG-PET parameters for successful tapering and/or discontinuation of TNFi.
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http://dx.doi.org/10.1093/rheumatology/keab842DOI Listing
November 2021

Nuclear medicine theranostics comes of age.

Lancet Oncol 2021 11;22(11):1497-1498

Department of Biomedical Sciences, Humanitas University, Milan, Italy; Humanitas Clinical and Research Center, IRCCS, Milan, Italy; Radboud University Medical Center, Nijmegen, Netherlands; Department of Radiology and Nuclear Medicine, Rijnstate Hospital, Arnhem, Netherlands. Electronic address:

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http://dx.doi.org/10.1016/S1470-2045(21)00540-4DOI Listing
November 2021

Prospective Evaluation of Whole-Body MRI versus FDG PET/CT for Lesion Detection in Participants with Myeloma.

Radiol Imaging Cancer 2021 09;3(5):e210048

From the Royal Marsden Hospital Foundation NHS Trust, Fulham Rd, London SW3 6JJ, England (C.M., B.S., D.L., D.M.K., K.B., C.P., A.R., K.D., J.C., V.M., S.S., J.W., W.J.G.O., M.F.K.); The Institute of Cancer Research, London, England (C.M., N.P., D.M.K., C.P., J.W., M.B., W.J.G.O., M.F.K.); Epsom and St Helier University Hospitals NHS Trust, Epsom, England (S.S.); Croydon University Hospital, Croydon, England (B.C.); University College London Hospital NHS Foundation Trust, London, England (C.K.); and Surrey and Sussex Healthcare NHS Trust, Redhill, England (P.K.).

Purpose To compare disease detection of myeloma using contemporary whole-body (WB) MRI and fluorine 18 (F) fluorodeoxyglucose (FDG) PET/CT protocols and to correlate imaging with laboratory estimates of disease burden, including molecular characteristics. Materials and Methods In this observational, prospective study, participants were recruited from November 2015 to March 2018 who had a diagnosis of myeloma, who were planned to undergo chemotherapy and autologous stem cell transplantation, and who underwent baseline WB-MRI and FDG PET/CT (ClinicalTrials.gov identifier NCT02403102). Baseline clinical data, including genetics, were collected. Paired methods were used to compare burden and patterns of disease. Results Sixty participants (mean age, 60 years ± 9 [standard deviation]; 35 men) underwent baseline WB-MRI and FDG PET/CT. WB-MRI showed significantly higher detection for focal lesions at all anatomic sites (except ribs, scapulae, and clavicles) and for diffuse disease at all sites. Two participants presented with two or more focal lesions smaller than 5 mm only at WB-MRI but not FDG PET/CT. Participants with diffuse disease at MRI had higher plasma cell infiltration (percentage of nucleated cells: median, 60% [interquartile range {IQR}, 50%-61%] vs 15% [IQR, 4%-50%]; = .03) and paraprotein levels (median, 32.0 g/L [IQR, 24.0-48.0 g/L] vs 20.0 g/L [IQR, 12.0-22.6 g/L]; = .02) compared with those without diffuse disease. All genetically high-risk tumors showed diffuse infiltration at WB-MRI. Conclusion WB-MRI helped detect a higher number of myeloma lesions than FDG PET/CT, and diffuse disease detected at WB-MRI correlated with laboratory measures of disease burden and molecular markers of risk. MR-Imaging, Skeletal-Appendicular, Skeletal-Axial, Bone Marrow, Hematologic Diseases, Oncology Clinical trial registration no. NCT02403102. © RSNA, 2021.
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http://dx.doi.org/10.1148/rycan.2021210048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8489453PMC
September 2021

Radium-223 Treatment of Patients with Metastatic Castration Resistant Prostate Cancer: Biomarkers for Stratification and Response Evaluation.

Cancers (Basel) 2021 Aug 27;13(17). Epub 2021 Aug 27.

Department of Medical Oncology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.

Radium-223 dichloride ([Ra]RaCl; Ra-223) is a targeted alpha-emitting radiopharmaceutical which results in an overall survival and health related quality of life (HRQoL) benefit in symptomatic patients with metastatic castration resistant prostate cancer (mCRPC) and predominantly bone metastasis. Although effective, options to select patients who will derive treatment benefit and to monitor and predict treatment outcomes are limited. PSA response and radiographic evaluation are commonly used in mCRPC treatment assessment but are not informative in Ra-223 treated patients. Consequently, there is a clear need for predictive and prognostic tools. In this review, we discuss the physiology of bone metastases and the mechanism of action and efficacy of Ra-223 treatment, as well as offering an outline of current innovative prognostic and predictive biomarkers.
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http://dx.doi.org/10.3390/cancers13174346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431634PMC
August 2021

A Joint Statement from the American Thyroid Association, the European Association of Nuclear Medicine, the European Thyroid Association, the Society of Nuclear Medicine and Molecular Imaging on Current Diagnostic and Theranostic Approaches in the Management of Thyroid Cancer.

Thyroid 2021 07 23;31(7):1009-1019. Epub 2021 Jun 23.

American Thyroid Association, Falls Church, Virginia, USA.

The American Thyroid Association (ATA), the European Association of Nuclear Medicine, the European Thyroid Association, and the Society of Nuclear Medicine and Molecular Imaging have established an intersocietal working group to address the current controversies and evolving concepts in thyroid cancer management and therapy. The working group annually identifies topics that may significantly impact clinical practice and publishes expert opinion articles reflecting intersocietal collaboration, consensus, and suggestions for further research to address these important management issues. In 2019, the intersocietal working group identified the following topics for review and interdisciplinary discussion: (i) perioperative risk stratification, (ii) the role of diagnostic radioactive iodine (RAI) imaging in initial staging, and (iii) indicators of response to RAI therapy. The intersocietal working group agreed that (i) initial patient management decisions should be guided by perioperative risk stratification that should include the eighth edition American Joint Committee on Cancer staging system to predict disease specific mortality, the modified 2009 ATA risk stratification system to estimate structural disease recurrence, with judicious incorporation of molecular theranostics to further refine management recommendations; (ii) diagnostic RAI scanning in ATA intermediate risk patients should be utilized selectively rather than being considered mandatory or not necessary for all patients in this category; and (iii) a consistent semiquantitative reporting system should be used for response evaluations after RAI therapy until a reproducible and clinically practical quantitative system is validated.
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http://dx.doi.org/10.1089/thy.2020.0826DOI Listing
July 2021

Medical imaging and nuclear medicine: a Lancet Oncology Commission.

Lancet Oncol 2021 04 4;22(4):e136-e172. Epub 2021 Mar 4.

Tumour Targeting Laboratory, Olivia Newton-John Cancer Research Institute, Melbourne, VIC, Australia; Department of Molecular Imaging and Therapy, Austin Health, Melbourne, VIC, Australia; School of Cancer Medicine, La Trobe University, Melbourne, VIC, Australia; Department of Medicine, University of Melbourne, Melbourne, VIC, Australia.

The diagnosis and treatment of patients with cancer requires access to imaging to ensure accurate management decisions and optimal outcomes. Our global assessment of imaging and nuclear medicine resources identified substantial shortages in equipment and workforce, particularly in low-income and middle-income countries (LMICs). A microsimulation model of 11 cancers showed that the scale-up of imaging would avert 3·2% (2·46 million) of all 76·0 million deaths caused by the modelled cancers worldwide between 2020 and 2030, saving 54·92 million life-years. A comprehensive scale-up of imaging, treatment, and care quality would avert 9·55 million (12·5%) of all cancer deaths caused by the modelled cancers worldwide, saving 232·30 million life-years. Scale-up of imaging would cost US$6·84 billion in 2020-30 but yield lifetime productivity gains of $1·23 trillion worldwide, a net return of $179·19 per $1 invested. Combining the scale-up of imaging, treatment, and quality of care would provide a net benefit of $2·66 trillion and a net return of $12·43 per $1 invested. With the use of a conservative approach regarding human capital, the scale-up of imaging alone would provide a net benefit of $209·46 billion and net return of $31·61 per $1 invested. With comprehensive scale-up, the worldwide net benefit using the human capital approach is $340·42 billion and the return per dollar invested is $2·46. These improved health and economic outcomes hold true across all geographical regions. We propose actions and investments that would enhance access to imaging equipment, workforce capacity, digital technology, radiopharmaceuticals, and research and training programmes in LMICs, to produce massive health and economic benefits and reduce the burden of cancer globally.
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http://dx.doi.org/10.1016/S1470-2045(20)30751-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444235PMC
April 2021

Consensus on molecular imaging and theranostics in neuroendocrine neoplasms.

Eur J Cancer 2021 03 12;146:56-73. Epub 2021 Feb 12.

Department of Nuclear Medicine, Universitätsklinikum, Essen, Germany. Electronic address:

Nuclear medicine plays an increasingly important role in the management neuroendocrine neoplasms (NEN). Somatostatin analogue (SSA)-based positron emission tomography/computed tomography (PET/CT) and peptide receptor radionuclide therapy (PRRT) have been used in clinical trials and approved by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). European Association of Nuclear Medicine (EANM) Focus 3 performed a multidisciplinary Delphi process to deliver a balanced perspective on molecular imaging and radionuclide therapy in well-differentiated neuroendocrine tumours (NETs). NETs form in cells that interact with the nervous system or in glands that produce hormones. These cells, called neuroendocrine cells, can be found throughout the body, but NETs are most often found in the abdomen, especially in the gastrointestinal tract. These tumours may also be found in the lungs, pancreas and adrenal glands. In addition to being rare, NETs are also complex and may be difficult to diagnose. Most NETs are non-functioning; however, a minority present with symptoms related to hypersecretion of bioactive compounds. NETs often do not cause symptoms early in the disease process. When diagnosed, substantial number of patients are already found to have metastatic disease. Several societies' guidelines address Neuroendocrine neoplasms (NENs) management; however, many issues are still debated, due to both the difficulty in acquiring strong clinical evidence in a rare and heterogeneous disease and the different availability of diagnostic and therapeutic options across countries. EANM Focus 3 reached consensus on employing gallium-labelled somatostatin analogue ([Ga]Ga-DOTA-SSA)-based PET/CT with diagnostic CT or magnetic resonance imaging (MRI) for unknown primary NET detection, metastatic NET, NET staging/restaging, suspected extra-adrenal pheochromocytoma/paraganglioma and suspected paraganglioma. Consensus was reached on employing fluorine-fluoro-2-deoxyglucose ([F]FDG) PET/CT in neuroendocrine carcinoma, G3 NET and in G1-2 NET with mismatched lesions (CT-positive/[Ga]Ga-DOTA-SSA-negative). Peptide receptor radionuclide therapy (PRRT) was recommended for second line treatment for gastrointestinal NET with [Ga]Ga-DOTA-SSA uptake in all lesions, in G1/G2 NET at disease progression, and in a subset of G3 NET provided all lesions are positive at [F]FDG and [Ga]Ga-DOTA-SSA. PRRT rechallenge may be used for in patients with stable disease for at least 1 year after therapy completion. An international consensus is not only a prelude to a more standardised management across countries but also serves as a guide for the direction to follow when designing new research studies.
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http://dx.doi.org/10.1016/j.ejca.2021.01.008DOI Listing
March 2021

Amyloid-PET and F-FDG-PET in the diagnostic investigation of Alzheimer's disease and other dementias.

Lancet Neurol 2020 11;19(11):951-962

Department of Neurodegenerative Disease, Institute of Neurology, University College London, London, UK; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; UK Dementia Research Institute at University College London, London, UK.

Various biomarkers are available to support the diagnosis of neurodegenerative diseases in clinical and research settings. Among the molecular imaging biomarkers, amyloid-PET, which assesses brain amyloid deposition, and F-fluorodeoxyglucose (F-FDG) PET, which assesses glucose metabolism, provide valuable and complementary information. However, uncertainty remains regarding the optimal timepoint, combination, and an order in which these PET biomarkers should be used in diagnostic evaluations because conclusive evidence is missing. Following an expert panel discussion, we reached an agreement on the specific use of the individual biomarkers, based on available evidence and clinical expertise. We propose a diagnostic algorithm with optimal timepoints for these PET biomarkers, also taking into account evidence from other biomarkers, for early and differential diagnosis of neurodegenerative diseases that can lead to dementia. We propose three main diagnostic pathways with distinct biomarker sequences, in which amyloid-PET and F-FDG-PET are placed at different positions in the order of diagnostic evaluations, depending on clinical presentation. We hope that this algorithm can support diagnostic decision making in specialist clinical settings with access to these biomarkers and might stimulate further research towards optimal diagnostic strategies.
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http://dx.doi.org/10.1016/S1474-4422(20)30314-8DOI Listing
November 2020

Radiation exposure awareness from patients undergoing nuclear medicine diagnostic 99mTc-MDP bone scans and 2-deoxy-2-(18F) fluoro-D-glucose PET/computed tomography scans.

Nucl Med Commun 2020 Jun;41(6):582-588

The Royal Marsden Hospital NHS Foundation Trust.

Introduction: Medical imaging is on average the largest source of artificial radiation exposure worldwide. This study seeks to understand patient's awareness of radiation exposure derived from nuclear medicine diagnostic scans and assess if current information provided by leaflets is adequate.

Methods: Single-centre cross-sectional questionnaire study applied to bone scan and FDG PET/computed tomography patients, at a nuclear medicine and PET/computed tomography department over a 15-week period in 2018. Questionnaires on dose comparators were designed in collaboration with patients, public, and experts in radiation exposure. Qualitative data were analysed using thematic analysis and quantitative data using SPSS (V. 24).

Results: A total of 102 questionnaires were completed (bone scan = 50; FDG PET/computed tomography = 52). Across both groups, 33/102 (32.4%) patients reported having a reasonable understanding of nuclear medicine and 21/102 (20.6%) reported a reasonable knowledge of ionising radiations. When asked to compare the exposure dose of respective scans with common comparators 8/50 (16%) of bone scan patients and 11/52 (21.2%) FDG PET/computed tomography answered correctly. On leaflet information, 15/85 (17.6%) patients reported the leaflets do not provide enough information on radiation exposure and of these 10/15 (66.7%) commented the leaflets should incorporate more information on radiation exposure dose.

Conclusion: More observational and qualitative studies in collaboration with patients are warranted to evaluate patients' understanding and preferences in communication of radiation exposure from nuclear medicine imaging. This will ensure communication tools and guidelines developed to comply with ionising radiation (medical exposure) regulation 2017 are according to patients needs and preferences.
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http://dx.doi.org/10.1097/MNM.0000000000001177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242175PMC
June 2020

Follow-up imaging after cryoablation of clear cell renal cell carcinoma is feasible using single photon emission computed tomography with In-girentuximab.

Eur J Nucl Med Mol Imaging 2020 07 25;47(8):1864-1870. Epub 2019 Nov 25.

Department of Urology, Radboud University Medical Center, 6500, HB, Nijmegen, the Netherlands.

Purpose: Detection of residual or recurrent vital renal tumor on follow-up (FU) cross-sectional imaging after ablative therapy is challenging. The specific and high expression levels of carbonic anhydrase IX (CAIX) in clear cell renal cell carcinoma (ccRCC) makes it a suitable target for imaging using radiolabeled anti-CAIX antibody girentuximab. The objective of this study was to evaluate the feasibility of targeted FU imaging 1 month after cryoablation of ccRCC using single photon emission computed tomography (SPECT) after In-labeled girentuximab administration.

Methods: In this prospective study 16 patients underwent In-girentuximab-SPECT before MR-guided renal cryoablation between February 2015 and September 2018. In case of tumor targeting In-girentuximab-SPECT was repeated 1 month following MR-guided cryoablation. Presence of residual or recurrent vital tumor was assessed on contrast-enhanced cross-sectional imaging during further FU. The standard FU imaging protocol consisted of MRI/CT scans at 1, 3, 6, 12, and 18 months and annually thereafter.

Results: A total of 10 (63%) patients showed positive tumor targeting on In-girentuximab-SPECT before cryoablation and 9 ( 56%) were eligible to undergo FU SPECT. Of the 9 In-girentuximab-SPECT FU scans, 8 (89%) were considered negative. One (11%) scan showed uptake suggestive for residual vital tumor. Six months after treatment, FU CT showed contrast enhancement suggestive for residual/recurrent disease in the ablated zone at the site of the In-girentuximab uptake after treatment. During a mean FU of 21 months (range 1-33) no other cases with residual/recurrent disease were detected.

Conclusion: FU imaging with In-girentuximab-SPECT is feasible after ccRCC cryoablation and may contribute to early detection of residual or recurrent disease.
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http://dx.doi.org/10.1007/s00259-019-04613-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299921PMC
July 2020

EAU-ESMO Consensus Statements on the Management of Advanced and Variant Bladder Cancer-An International Collaborative Multistakeholder Effort: Under the Auspices of the EAU-ESMO Guidelines Committees.

Eur Urol 2020 02 19;77(2):223-250. Epub 2019 Nov 19.

Department of Biomedical Sciences, Humanitas University, Milan, Italy; Humanitas Research Hospital, Milan, Italy.

Background: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial.

Objective: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management.

Design: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts prior to voting during a consensus conference.

Setting: Online Delphi survey and consensus conference.

Participants: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management.

Outcome Measurements And Statistical Analysis: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), and 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus).

Results And Limitations: Overall, 116 statements were included in the Delphi survey. Of these statements, 33 (28%) achieved level 1 consensus and 49 (42%) achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease, and the evolving role of checkpoint inhibitor therapy in metastatic disease.

Conclusions: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time when further evidence is available to guide our approach.

Patient Summary: This report summarises findings from an international, multistakeholder project organised by the EAU and ESMO. In this project, a steering committee identified areas of bladder cancer management where there is currently no good-quality evidence to guide treatment decisions. From this, they developed a series of proposed statements, 71 of which achieved consensus by a large group of experts in the field of bladder cancer. It is anticipated that these statements will provide further guidance to health care professionals and could help improve patient outcomes until a time when good-quality evidence is available.
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http://dx.doi.org/10.1016/j.eururo.2019.09.035DOI Listing
February 2020

A Clinical Feasibility Study to Image Angiogenesis in Patients with Arteriovenous Malformations Using Ga-RGD PET/CT.

J Nucl Med 2020 02 13;61(2):270-275. Epub 2019 Sep 13.

Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.

Arteriovenous malformations (AVMs) have an inherent capacity to form new blood vessels, resulting in excessive lesion growth, and this process is further triggered by the release of angiogenic factors. Ga-labeled arginine-glycine-aspartate tripeptide sequence (RGD) PET/CT imaging may provide insight into the angiogenic status and treatment response of AVMs. This clinical feasibility study was performed to demonstrate that Ga-RGD PET/CT imaging can be used to quantitatively assess angiogenesis in peripheral AVMs. Ten patients with a peripheral AVM (mean age, 40 y; 4 men and 6 women) and scheduled for endovascular embolization treatment were prospectively included. All patients underwent Ga-RGD PET/CT imaging 60 min after injection (mean dose, 207 ± 5 MBq). Uptake in the AVM, blood pool, and muscle was quantified as SUV and SUV, and a descriptive analysis of the PET/CT images was performed. Furthermore, immunohistochemical analysis was performed on surgical biopsy sections of peripheral AVMs to investigate the expression pattern of integrin αβ Ga-RGD PET/CT imaging showed enhanced uptake in all AVM lesions (mean SUV, 3.0 ± 1.1; mean SUV, 2.2 ± 0.9). Lesion-to-blood and lesion-to-muscle ratios were 3.5 ± 2.2 and 4.6 ± 2.8, respectively. Uptake in blood and muscle was significantly higher in AVMs than in background tissue ( = 0.0006 and = 0.0014, respectively). Initial observations included uptake in multifocal AVM lesions and enhanced uptake in intraosseous components in those AVM cases affecting bone integrity. Immunohistochemical analysis revealed cytoplasmatic and membranous integrin αβ expression in the endothelial cells of AVMs. This feasibility study showed increased uptake in AVMs with angiogenic activity, compared with surrounding tissue without angiogenic activity, suggesting that Ga-RGD PET/CT imaging can be used as a tool to quantitatively determine angiogenesis in AVMs. Further studies will be conducted to explore the potential of Ga-RGD PET/CT imaging for guiding current treatment decisions and for assessing response to antiangiogenic treatment.
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http://dx.doi.org/10.2967/jnumed.119.231167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7100027PMC
February 2020

Emerging Vistas in Alpha Therapy-PSMA and Soft-Tissue Metastases.

Authors:
Wim J G Oyen

J Med Imaging Radiat Sci 2019 Dec 22;50(4S1):S47-S48. Epub 2019 Aug 22.

Department of Biomedical Sciences, Humanitas University, Milan, Italy; Department of Radiology and Nuclear Medicine, Rijnstate Hospital, Arnhem, The Netherlands; Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address:

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http://dx.doi.org/10.1016/j.jmir.2019.07.001DOI Listing
December 2019

EANM commitment towards involvement and engagement of patients and the public: learning from the UK experience.

Eur J Nucl Med Mol Imaging 2019 Oct 2;46(11):2218-2219. Epub 2019 Aug 2.

The European Association of Nuclear Medicine, Vienna, Austria.

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http://dx.doi.org/10.1007/s00259-019-04457-7DOI Listing
October 2019

Imaging Diagnosis and Follow-up of Advanced Prostate Cancer: Clinical Perspectives and State of the Art.

Radiology 2019 08 25;292(2):273-286. Epub 2019 Jun 25.

From the Radiomics Group, Vall D'Hebron Institute of Oncology, Barcelona, Spain (R.P.L.); Departments of Radiology (N.T., D.M.K.) and Nuclear Medicine (W.J.G.O.), Royal Marsden NHS Foundation Trust, Downs Road, Sutton SM2 5PT, England; Paul Strickland Scanner Centre, Mount Vernon Hospital, Northwood, England (A.R.P.); Divisions of Radiotherapy and Imaging (W.J.G.O., D.M.K.) and Clinical Studies & Prostate Cancer Targeted Therapy Group (J.d.B.), Institute of Cancer Research, Sutton, England; Departments of Radiology (S.F.) and Genitourinary Oncology Service and Medicine (M.J.M.), Memorial Sloan-Kettering Cancer Center, New York, NY; Department of Oncology and Haematology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland (H.A.V., A.O.); Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Switzerland (H.A.V., A.O.); and Department of Medicine, Weill Cornell Medicine, New York, NY (M.J.M.).

The management of advanced prostate cancer has changed substantially with the availability of multiple effective novel treatments, which has led to improved disease survival. In the era of personalized cancer treatments, more precise imaging may help physicians deliver better care. More accurate local staging and earlier detection of metastatic disease, accurate identification of oligometastatic disease, and optimal assessment of treatment response are areas where modern imaging is rapidly evolving and expanding. Next-generation imaging modalities, including whole-body MRI and molecular imaging with combined PET and CT and combined PET and MRI using novel radiopharmaceuticals, create new opportunities for imaging to support and refine management pathways in patients with advanced prostate cancer. This article demonstrates the potential and challenges of applying next-generation imaging to deliver the clinical promise of treatment breakthroughs.
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http://dx.doi.org/10.1148/radiol.2019181931DOI Listing
August 2019

Lesion detection by [Zr]Zr-DFO-girentuximab and [F]FDG-PET/CT in patients with newly diagnosed metastatic renal cell carcinoma.

Eur J Nucl Med Mol Imaging 2019 Aug 6;46(9):1931-1939. Epub 2019 Jun 6.

Department of Medical Oncology, Radboud University Medical Center Nijmegen, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.

Purpose: The main objective of this preliminary analysis of the IMaging PAtients for Cancer drug selecTion (IMPACT)-renal cell cancer (RCC) study is to evaluate the lesion detection of baseline contrast-enhanced CT, [Zr]Zr-DFO-girentuximab-PET/CT and [F]FDG-PET/CT in detecting ccRCC lesions in patients with a good or intermediate prognosis metastatic clear cell renal cell carcinoma (mccRCC) according to the International Metastatic Database Consortium (IMDC) risk model.

Methods: Between February 2015 and March 2018, 42 newly diagnosed mccRCC patients with good or intermediate prognosis, eligible for watchful waiting, were included. Patients underwent CT, [Zr]Zr-DFO-girentuximab-PET/CT and [F]FDG-PET/CT at baseline. Scans were independently reviewed and lesions of ≥10 mm and lymph nodes of ≥15 mm at CT were analyzed. For lesions with [Zr]Zr-DFO-girentuximab or [F]FDG-uptake visually exceeding background uptake, maximum standardized uptake values (SUV) were measured.

Results: A total of 449 lesions were detected by ≥1 modality (median per patient: 7; ICR 4.25-12.75) of which 42% were in lung, 22% in lymph nodes and 10% in bone. Combined [Zr]Zr-DFO-girentuximab-PET/CT and CT detected more lesions than CT alone: 91% (95%CI: 87-94) versus 56% (95%CI: 50-62, p = 0.001), respectively, and more than CT and [F]FDG-PET/CT combined (84% (95%CI:79-88, p < 0.005). Both PET/CTs detected more bone and soft tissue lesions compared to CT alone.

Conclusions: The addition of [Zr]Zr-DFO-girentuximab-PET/CT and [F]FDG-PET/CT to CT increases lesion detection compared to CT alone in newly diagnosed good and intermediate prognosis mccRCC patients eligible for watchful waiting.
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http://dx.doi.org/10.1007/s00259-019-04358-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6647180PMC
August 2019

EANM Focus 1: one small step for two men, one giant leap for a specialty.

Eur J Nucl Med Mol Imaging 2019 Jul 24;46(7):1400-1401. Epub 2019 Apr 24.

Department of Biomedical Sciences, Humanitas University, Milan, Italy.

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http://dx.doi.org/10.1007/s00259-019-04326-3DOI Listing
July 2019

Impact of Ga-68-PSMA PET/CT on management in prostate cancer patients with very early biochemical recurrence after radical prostatectomy.

Eur J Nucl Med Mol Imaging 2019 Apr 8;46(4):901-907. Epub 2019 Jan 8.

Division of Radiotherapy and Imaging, Centre for Cancer Imaging/SRD, The Institute of Cancer Research, 15 Cotswold Road, London, Sutton, SM2 5NG, UK.

Purpose: With the availability of ultra-sensitive PSA assays, early biochemical relapse (eBCR) of prostate cancer is increasingly being detected at values much lower than the conventional threshold of 0.2 ng/ml. Accurate localisation of disease in this setting may allow treatment modification and improved outcomes, especially in patients with pelvis-confined or extra-pelvic oligometastasis (defined as up to three pelvic nodal or distant sites). We aimed to measure the detection rate of [68]Ga-PSMA-HBNED-CC (PSMA)-PET/CT and its influence on patient management in eBCR of prostate cancer following radical prostatectomy (RP).

Methods: We retrospectively identified 28 patients who underwent PSMA-PET/CT for post-RP eBCR (PSA < 0.5 ng/ml) at our tertiary care cancer centre. Two nuclear medicine physicians independently recorded the sites of PSMA-PET/CT positivity. Multidisciplinary meeting records were accessed to determine changes in management decisions following PSMA-PET/CT scans.

Results: The mean age of patients was 65.6 years (range: 50-76.2 years); median PSA was 0.22 ng/ml (interquartile range: 0.15 ng/ml to 0.34 ng/ml). Thirteen patients (46.4%) had received radiotherapy in the past. PSMA-PET/CT was positive in 17 patients (60.7%). Only one patient had polymetastasis (> 3 sites); the remainder either had prostatectomy bed recurrence (n = 2), pelvic oligometastasis (n = 10), or extra-pelvic oligometastasis (n = 4). PSMA-PET/CT resulted in management change in 12 patients (42.8%), involving stereotactic body radiotherapy (n = 6), salvage radiotherapy (n = 4), and systemic treatment (n = 2).

Conclusions: Our findings show that PSMA-PET/CT has a high detection rate in the eBCR setting following RP, with a large proportion of patients found to have fewer than three lesions. PSMA-PET/CT may be of value in patients with early PSA failure, and impact on the choice of potentially curative salvage treatments.
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http://dx.doi.org/10.1007/s00259-018-4249-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6450837PMC
April 2019

The EANM practical guidelines for sentinel lymph node localisation in oral cavity squamous cell carcinoma.

Eur J Nucl Med Mol Imaging 2019 03 18;46(3):623-637. Epub 2018 Dec 18.

University Hospital San Pedro and Centre for Biomedical Research of La Rioja (CIBIR), Logroño, La Rioja, Spain.

Purpose: Sentinel lymph node biopsy is an essential staging tool in patients with clinically localized oral cavity squamous cell carcinoma. The harvesting of a sentinel lymph node entails a sequence of procedures with participation of specialists in nuclear medicine, radiology, surgery, and pathology. The aim of this document is to provide guidelines for nuclear medicine physicians performing lymphoscintigraphy for sentinel lymph node detection in patients with early N0 oral cavity squamous cell carcinoma.

Methods: These practice guidelines were written and have been approved by the European Association of Nuclear Medicine (EANM) and the International Atomic Energy Agency (IAEA) to promote high-quality lymphoscintigraphy. The final result has been discussed by distinguished experts from the EANM Oncology Committee, and national nuclear medicine societies. The document has been endorsed by the Society of Nuclear Medicine and Molecular Imaging (SNMMI). These guidelines, together with another two focused on Surgery and Pathology (and published in specialised journals), are part of the synergistic efforts developed in preparation for the "2018 Sentinel Node Biopsy in Head and Neck Consensus Conference".

Conclusion: The present practice guidelines will help nuclear medicine practitioners play their essential role in providing high-quality lymphatic mapping for the care of early N0 oral cavity squamous cell carcinoma patients.
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http://dx.doi.org/10.1007/s00259-018-4235-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351508PMC
March 2019

Consensus on molecular imaging and theranostics in prostate cancer.

Lancet Oncol 2018 12;19(12):e696-e708

Lehrstuhl für Pharmazeutische Radiochemie, Technische Universität München, Garching, Germany.

Rapid developments in imaging and treatment with radiopharmaceuticals targeting prostate cancer pose issues for the development of guidelines for their appropriate use. To tackle this problem, international experts representing medical oncologists, urologists, radiation oncologists, radiologists, and nuclear medicine specialists convened at the European Association of Nuclear Medicine Focus 1 meeting to deliver a balanced perspective on available data and clinical experience of imaging in prostate cancer, which had been supported by a systematic review of the literature and a modified Delphi process. Relevant conclusions included the following: diphosphonate bone scanning and contrast-enhanced CT are mentioned but rarely recommended for most patients in clinical guidelines; MRI (whole-body or multiparametric) and prostate cancer-targeted PET are frequently suggested, but the specific contexts in which these methods affect practice are not established; sodium fluoride-18 for PET-CT bone scanning is not widely advocated, whereas gallium-68 or fluorine-18 prostate-specific membrane antigen gain acceptance; and, palliative treatment with bone targeting radiopharmaceuticals (rhenium-186, samarium-153, or strontium-89) have largely been replaced by radium-223 on the basis of the survival benefit that was reported in prospective trials, and by other systemic therapies with proven survival benefits. Although the advances in MRI and PET-CT have improved the accuracy of imaging, the effects of these new methods on clinical outcomes remains to be established. Improved communication between imagers and clinicians and more multidisciplinary input in clinical trial design are essential to encourage imaging insights into clinical decision making.
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http://dx.doi.org/10.1016/S1470-2045(18)30604-1DOI Listing
December 2018

Affibody-Based PET Imaging to Guide EGFR-Targeted Cancer Therapy in Head and Neck Squamous Cell Cancer Models.

J Nucl Med 2019 03 13;60(3):353-361. Epub 2018 Sep 13.

Division of Radiotherapy and Imaging, Institute of Cancer Research, London, United Kingdom; and

In head and neck squamous cell cancer, the human epidermal growth factor receptor 1 (EGFR) is the dominant signaling molecule among all members of the family. So far, cetuximab is the only approved anti-EGFR monoclonal antibody used for the treatment of head and neck squamous cell cancer, but despite the benefits of adding it to standard treatment regimens, attempts to define a predictive biomarker to stratify patients for cetuximab treatment have been unsuccessful. We hypothesized that imaging with EGFR-specific radioligands may facilitate noninvasive measurement of EGFR expression across the entire tumor burden and allow for dynamic monitoring of cetuximab-mediated changes in receptor expression. EGFR-specific Affibody molecule (Z) was radiolabeled with Zr and F. The radioligands were characterized in vitro and in mice bearing subcutaneous tumors with varying levels of EGFR expression. The protein dose for imaging studies was assessed by injecting Zr-deferoxamine-Z (2.4-3.6 MBq, 2 μg) either together with or 30 min after increasing amounts of unlabeled Z (1, 5, 10, 15, and 20 μg). PET images were acquired at 3, 24, and 48 h after injection, and the image quantification data were correlated with the biodistribution results. The EGFR expression and biodistribution of the tracer were assessed ex vivo by immunohistochemistry, Western blot, and autoradiography. To downregulate the EGFR level, treatment with cetuximab was performed, and F-aluminium fluoride-NOTA-Z (12 μg, 1.5-2 MBq/mouse) was used to monitor receptor changes. In vivo studies demonstrated that coinjecting 10 μg of nonlabeled molecules with Zr-deferoxamine-Z allows for clear tumor visualization 3 h after injection. The radioconjugate tumor accumulation was EGFR-specific, and PET imaging data showed a clear differentiation between xenografts with varying EGFR expression levels. A strong correlation was observed between PET analysis, ex vivo estimates of tracer concentration, and receptor expression in tumor tissues. Additionally, F-aluminium fluoride-NOTA-Z could measure receptor downregulation in response to EGFR inhibition. Z-based radioconjugates can assess different levels of EGFR level in vivo and measure receptor expression changes in response to cetuximab, indicating a potential for assessment of adequate treatment dosing with anti-EGFR antibodies.
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http://dx.doi.org/10.2967/jnumed.118.216069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6424230PMC
March 2019

Managing Nonmetastatic Castration-resistant Prostate Cancer.

Eur Urol 2019 02 14;75(2):285-293. Epub 2018 Aug 14.

The Royal Marsden Hospital and The Institute of Cancer Research, London, UK. Electronic address:

Context: Patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) have rising prostate-specific antigen (PSA) and castrate testosterone levels, with no radiological findings of metastatic disease on computed tomography and bone scan. Given recent drug approvals for nmCRPC, with many other therapeutics and imaging modalities being developed, management of nmCRPC is a rapidly evolving field that merits detailed investigation.

Objective: To review current nmCRPC management practices and identify opportunities for improving care of nmCRPC patients.

Evidence Acquisition: A literature search up to July 2018 was conducted, including clinical trials and clinical practice guidelines (National Comprehensive Cancer Network, European Society for Medical Oncology, European Association of Urology, Prostate Cancer Clinical Trials Working Group, Prostate Cancer Radiographic Assessments for Detection of Advanced Recurrence). Keywords included prostate cancer, nonmetastatic, castration resistance, rising PSA, and biochemical relapse.

Evidence Synthesis: Recommendations regarding indications for, and frequency of, imaging and PSA testing, as well as for initiating systemic therapy in nmCRPC are based on PSA rise kinetics and symptoms. Both enzalutamide and apalutamide have been shown to significantly increase metastasis-free survival in phase III placebo-controlled randomised trials in nmCRPC patients with PSA doubling time (DT) ≤10 mo. The expected impact of new imaging techniques in the assessment of nmCRPC is also reviewed.

Conclusions: nmCRPC is a heterogeneous disease; while observation may be an option for some patients, enzalutamide and apalutamide may be appropriate to treat nmCRPC patients with PSA-DT ≤10 mo. The emergence of more accurate imaging modalities as well as circulating tumour biomarker assays will likely redefine the assessment of nmCRPC in the near future.

Patient Summary: Herein, we review key literature and clinical practice guidelines to summarise the optimal management of patients with prostate cancer and rising prostate-specific antigen despite castrate testosterone levels, but with no evidence of distant metastasis on traditional imaging. New drugs are being developed for this disease setting; novel imaging and tumour biomarker blood tests are likely to define this disease state more accurately.
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http://dx.doi.org/10.1016/j.eururo.2018.07.035DOI Listing
February 2019

Tumor to cervical spinal cord standardized uptake ratio (SUR) improves the reproducibility of F-FDG-PET based tumor segmentation in head and neck squamous cell carcinoma in a multicenter setting.

Radiother Oncol 2019 01 10;130:39-45. Epub 2018 Jul 10.

Department of Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands; The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, United Kingdom.

Background: In quantitative FDG-PET data analysis, normalization of the standardized uptake value (SUV) with an internal image-derived standard improves its reproducibility. In this study, the cervical spinal cord is proposed as an internal standard that is within the field of view of the radiotherapy planning PET/CT-scan in head and neck cancer. The aim is to evaluate if the tumor to cervical spinal cord standardized uptake ratio (SUR) can improve the reproducibility of a model to determine the metabolic tumor volume (MTV) on FDG-PET/CT in a multicenter setting.

Materials And Methods: Ninety-five radiotherapy planning FDG-PET/CT-scans of patients with head and neck cancer were analyzed using the Bland-Altman method to evaluate differences in FDG-uptake in the cervical spinal cord and the mediastinal blood pool. Non-linear regression analysis was used to determine the optimal MTV using the gross tumor volume (GTV) as ground truth and a spatial overlap-index as statistical validation metric. Reproducibility was evaluated using the Bland-Altman method and external validation was performed in an independent dataset consisting of 62 patients.

Results: Bland-Altman's analyses demonstrated equivalence of FDG-uptake in the mediastinal blood pool and the cervical spinal cord. Reproducibility of the models improved when using SUR instead of SUV. These results were confirmed in the validation cohort.

Conclusion: The use of the tumor to cervical spinal cord SUR instead of SUV improves the reproducibility of a model to determine the MTV on FDG-PET/CT in a multicenter setting. This study indicates that SUR may be preferred over SUV based approaches.
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http://dx.doi.org/10.1016/j.radonc.2018.06.037DOI Listing
January 2019

Vascular infection with outside-in vertebral destruction in chronic Q fever.

Lancet Infect Dis 2018 06;18(6):603

Department of Internal Medicine, Division of Infectious Diseases and Radboud Expert Centre for Q Fever, Radboud University Medical Center, Nijmegen 6500 HB, Netherlands.

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http://dx.doi.org/10.1016/S1473-3099(18)30272-XDOI Listing
June 2018

18F-fluorodeoxyglucose positron-emission tomography combined with computed tomography as a diagnostic tool in native valve endocarditis.

Nucl Med Commun 2018 Aug;39(8):747-752

Departments of Internal Medicine and Infectious Diseases.

Objective: The aim of the study was to investigate the value of F-fluorodeoxyglucose positron-emission tomography combined with computed tomography (F-FDG-PET/CT) in diagnosing native valve endocarditis (NVE).

Patients And Methods: All patients with bacteremia and suspicion of NVE between January 2013 and June 2016 were identified from the hospitals' register and retrospectively included if echocardiography and F-FDG-PET/CT were performed within 14 days. F-FDG-PET/CT scans were scored independently by two nuclear medicine physicians. F-FDG-PET/CT was compared with the modified-Duke criteria and a multidisciplinary consensus.

Results: A total of 88 patients were included. In 10 patients with definite NVE according to the modified-Duke criteria, three (30.0%) patients had increased F-FDG uptake in or around the heart valves and seven (70.0%) patients had no increased F-FDG uptake. In patients without definite NVE according to the modified-Duke criteria, 89.7% (70/78) of the patients had no increased F-FDG uptake in or around the heart valves. Of all 20 patients with NVE according to multidisciplinary consensus, nine (45.0%) patients had increased F-FDG uptake in or around the heart valves and 11 (55.0%) patients had a normal F-FDG-PET/CT result.

Conclusion: A negative F-FDG-PET/CT result should not be interpreted as an exclusion of NVE. In patients with possible or rejected NVE according to the modified-Duke criteria, F-FDG-PET/CT could be used in case of sustained suspicion of NVE owing to its high specificity in case of abnormal FDG uptake at the valve region. F-FDG-PET/CT is important for detecting metastatic infection which already warrants the need to perform F-FDG-PET/CT in all patients with suspected NVE.
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http://dx.doi.org/10.1097/MNM.0000000000000864DOI Listing
August 2018

Positron Emission Tomography/Computed Tomography with Zr-girentuximab Can Aid in Diagnostic Dilemmas of Clear Cell Renal Cell Carcinoma Suspicion.

Eur Urol 2018 09 3;74(3):257-260. Epub 2018 May 3.

Department of Urology, Radboudumc, Nijmegen, The Netherlands.

Based on the high expression of carbonic anhydrase IX (CAIX) in 95% of clear cell renal cell carcinoma (ccRCC), the anti-CAIX monoclonal antibody girentuximab can be used for the detection of ccRCC. This clinical study explores the value of Zr-labeled girentuximab positron emission tomography/computed tomography (PET/CT) imaging in diagnostic challenges regarding ccRCC. PET/CT imaging was performed 4 or 5 d after injection of Zr-girentuximab in patients with a primary renal mass (n=16) or a history of ccRCC (n=14). Scans were used for decision making (surgery/active surveillance) in case of indistinct renal masses. All resected PET-positive primary lesions proved to be ccRCC, while no lesion progression was seen in PET-negative masses. In patients suspected of recurrent/metastatic ccRCC, PET/CT with Zr-girentuximab was useful to confirm or exclude ccRCC, evaluate the extent of the disease, and differentiate from other cancers. In this group, Zr-girentuximab PET/CT resulted in a major change in clinical management in five patients (36%), while in three patients (21%) repeat biopsies could be avoided. We conclude that Zr-girentuximab PET/CT is a valuable diagnostic tool that can guide clinical decision making in case of diagnostic dilemmas concerning ccRCC suspicion.

Patient Summary: Positron emission tomography/computed tomography imaging with Zr-girentuximab can be a valuable diagnostic tool to identify clear cell renal cell carcinoma.
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http://dx.doi.org/10.1016/j.eururo.2018.04.026DOI Listing
September 2018

In Vivo Characterization of 4 Ga-Labeled Multimeric RGD Peptides to Image αβ Integrin Expression in 2 Human Tumor Xenograft Mouse Models.

J Nucl Med 2018 08 6;59(8):1296-1301. Epub 2018 Apr 6.

Department of Radiology and Nuclear Medicine, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands.

αβ integrins play an important role in angiogenesis and cell migration in cancer and are highly expressed on the activated endothelial cells of newly formed blood vessels. Here, we compare the targeting characteristics of 4 Ga-labeled multimeric cyclic arginine-glycine-aspartate (RGD)-based tracers in an αβ integrin-expressing tumor model and a tumor model in which αβ integrin is expressed solely on the neovasculature. Female BALB/c nude mice were subcutaneously injected with SK-RC-52 (αβ integrin-positive) or FaDu (αβ integrin-negative) tumor cells. Ga-labeled DOTA-(RGD), TRAP-(RGD), FSC-(RGD), or THP-(RGD) was intravenously administered to the mice (0.5 nmol per mouse, 10-20 MBq), followed by small-animal PET/CT imaging and ex vivo biodistribution studies 1 h after injection. Nonspecific uptake of the tracers in both models was determined by coinjecting an excess of unlabeled DOTA-(RGD) (50 nmol) along with the radiolabeled tracers. Imaging and biodistribution data showed specific uptake in the tumors for each tracer in both models. Tumor uptake of Ga-FSC-(RGD) was significantly higher than that of Ga-DOTA-(RGD), Ga-TRAP-(RGD), or Ga-THP-(RGD) in the SK-RC-52 model but not in the FaDu model, in which Ga-FSC-(RGD) showed significantly higher tumor uptake than Ga-TRAP-(RGD) Most importantly, differences were also observed in normal tissues and in tumor-to-blood ratios. All tracers showed sufficient targeting of αβ integrin expression to allow for tumor detection. Although the highest tumor uptake was found for Ga-FSC-(RGD) and Ga-THP-(RGD) in the SK-RC-52 and FaDu models, respectively, selection of the optimal tracer for specific diagnostic applications also depends on tumor-to-blood ratio and uptake in normal tissues; these factors should therefore also be considered.
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http://dx.doi.org/10.2967/jnumed.117.206979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6175042PMC
August 2018

Fever of Unknown Origin: the Value of FDG-PET/CT.

Semin Nucl Med 2018 03 8;48(2):100-107. Epub 2017 Dec 8.

Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Nuclear Medicine, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London, United Kingdom. Electronic address:

Fever of unknown origin (FUO) is commonly defined as fever higher than 38.3°C on several occasions during at least 3 weeks with uncertain diagnosis after a number of obligatory investigations. The differential diagnosis of FUO can be subdivided in four categories: infections, malignancies, noninfectious inflammatory diseases, and miscellaneous causes. In most cases of FUO, there is an uncommon presentation of a common disease. FDG-PET/CT is a sensitive diagnostic technique for the evaluation of FUO by facilitating anatomical localization of focally increased FDG uptake, thereby guiding further diagnostic tests to achieve a final diagnosis. FDG-PET/CT should become a routine procedure in the workup of FUO when diagnostic clues are absent. FDG-PET/CT appears to be a cost-effective routine imaging technique in FUO by avoiding unnecessary investigations and reducing the duration of hospitalization.
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http://dx.doi.org/10.1053/j.semnuclmed.2017.11.004DOI Listing
March 2018
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