Publications by authors named "Andor W J M Glaudemans"

194 Publications

F-BMS986192 PET imaging of PD-L1 in metastatic melanoma patients with brain metastases treated with immune checkpoint inhibitors. A pilot study.

J Nucl Med 2021 Sep 9. Epub 2021 Sep 9.

University Medical Center Groningen, Netherlands.

Immune checkpoint inhibitors (ICI) targeting PD-1/PD-L1 frequently induces tumor response in metastatic melanoma patients. However, tumor response often takes months and may be heterogeneous. Consequently, additional local treatment for non-responsive metastases may be needed, especially in the case of brain metastases. Non-invasive imaging may allow the characterization of (brain) metastases to predict response. This pilot study uses F-BMS986192 PET for PD-L1 expression to explore the variability in metastatic tracer uptake and its relation to tumor response, with a special focus on brain metastases. Metastatic melanoma patients underwent whole-body F-BMS986192 PET/CT scanning before and 6 weeks after starting ICI therapy. F-BMS986192 uptake was measured in healthy tissues, organs, and tumor lesions. Tumor response was evaluated at 12 weeks using CT thorax/abdomen and MRI brain. RECIST v 1.1 was used to define therapy response per patient. Response per lesion was measured by the percentage change in lesion diameter. Toxicity was assessed according to Common Terminology Criteria for Adverse Events version 4.0. Baseline F-BMS986192 PET/CT was performed in 8 patients, with follow-up scans in 4 patients. The highest tracer uptake was observed in the spleen, bone marrow, kidneys, and liver. Tracer uptake in tumor lesions was heterogeneous. In total, 42 tumor lesions were identified at baseline with most lesions in the lungs ( = 21) and brain ( = 14). Tracer uptake was similar between tumor locations. F-BMS986192 uptake in lesions at baseline, corrected for blood pool activity, was negatively correlated with the change lesion diameter at response evaluation (r=-0.49, = 0.005), both in intra- and extracerebral lesions. Receiver operating characteristic (ROC) analysis demonstrated that F-BMS986192 uptake can discriminate between responding and nonresponding lesions with an area under the curve of 0.82. At the follow-up scan an increased F-BMS986192 uptake compared to baseline scan was correlated with an increased lesion diameter at response evaluation. In the follow-up F-BMS986192-PET scan of two patients, ICI-related toxicity (thyroiditis and colitis) was detected. In this pilot study, F-BMS986192 PET showed heterogeneous uptake in intra and extracerebral metastatic lesions in melanoma patients. Baseline F-BMS986192 uptake was able to predict an ICI treatment-induced reduction in lesion volume, whereas the follow-up PET scan allowed the detection of treatment-induced toxicity.
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http://dx.doi.org/10.2967/jnumed.121.262368DOI Listing
September 2021

The effects of molar activity on [F]FDOPA uptake in patients with neuroendocrine tumors.

EJNMMI Res 2021 Sep 8;11(1):88. Epub 2021 Sep 8.

Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Medical Imaging Center, University of Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands.

Background: 6-[F]fluoro-L-3,4-dihydroxyphenyl alanine ([F]FDOPA) is a commonly used PET tracer for the detection and staging of neuroendocrine tumors. In neuroendocrine tumors, [F]FDOPA is decarboxylated to [F]dopamine via the enzyme amino acid decarboxylase (AADC), leading to increased uptake when there is increased AADC activity. Recently, in our hospital, a new GMP compliant multi-dose production of [F]FDOPA has been developed, [F]FDOPA-H, resulting in a higher activity yield, improved molar activity and a lower administered mass than the conventional method ([F]FDOPA-L).

Aims: This study aimed to investigate whether the difference in molar activity affects the [F]FDOPA uptake at physiological sites and in tumor lesions, in patients with NET. It was anticipated that the specific uptake of [F]FDOPA-H would be equal to or higher than [F]FDOPA-L.

Methods: We retrospectively analyzed 49 patients with pathologically confirmed NETs and stable disease who underwent PET scanning using both [F]FDOPA-H and [F]FDOPA-L within a time span of 5 years. A total of 98 [F]FDOPA scans (49 [F]FDOPA-L and 49 [F]FDOPA-H with average molar activities of 8 and 107 GBq/mmol) were analyzed. The SUVmean was calculated for physiological organ uptake and SUVmax for tumor lesions in both groups for comparison, and separately in subjects with low tumor load (1-2 lesions) and higher tumor load (3-10 lesions).

Results: Comparable or slightly higher uptake was demonstrated in various physiological uptake sites in subjects scanned with [F]FDOPA-H compared to [F]FDOPA-L, with large overlap being present in the interquartile ranges. Tumor uptake was slightly higher in the [F]FDOPA-H group with 3-10 lesion (SUVmax 6.83 vs. 5.19, p < 0.001). In the other groups, no significant differences were seen between H and L.

Conclusion: [18F]FDOPA-H provides a higher activity yield, offering the possibility to scan more patients with one single production. Minor differences were observed in SUV's, with slight increases in uptake of [F]FDOPA-H in comparison to [F]FDOPA-L. This finding is not a concern for clinical practice, but could be of importance when quantifying follow-up scans while introducing new production methods with a higher molar activity of [F]FDOPA.
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http://dx.doi.org/10.1186/s13550-021-00829-zDOI Listing
September 2021

EANM recommendations based on systematic analysis of small animal radionuclide imaging in inflammatory musculoskeletal diseases.

EJNMMI Res 2021 Sep 6;11(1):85. Epub 2021 Sep 6.

Inflammation and Infection Committee EANM, Vienna, Austria.

Inflammatory musculoskeletal diseases represent a group of chronic and disabling conditions that evolve from a complex interplay between genetic and environmental factors that cause perturbations in innate and adaptive immune responses. Understanding the pathogenesis of inflammatory musculoskeletal diseases is, to a large extent, derived from preclinical and basic research experiments. In vivo molecular imaging enables us to study molecular targets and to measure biochemical processes non-invasively and longitudinally, providing information on disease processes and potential therapeutic strategies, e.g. efficacy of novel therapeutic interventions, which is of complementary value next to ex vivo (post mortem) histopathological analysis and molecular assays. Remarkably, the large body of preclinical imaging studies in inflammatory musculoskeletal disease is in contrast with the limited reports on molecular imaging in clinical practice and clinical guidelines. Therefore, in this EANM-endorsed position paper, we performed a systematic review of the preclinical studies in inflammatory musculoskeletal diseases that involve radionuclide imaging, with a detailed description of the animal models used. From these reflections, we provide recommendations on what future studies in this field should encompass to facilitate a greater impact of radionuclide imaging techniques on the translation to clinical settings.
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http://dx.doi.org/10.1186/s13550-021-00820-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421483PMC
September 2021

F-FDG-Uptake in Mediastinal Lymph Nodes in Suspected Prosthetic Valve Endocarditis: Predictor or Confounder?

Front Cardiovasc Med 2021 11;8:717774. Epub 2021 Aug 11.

Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.

Prosthetic valve endocarditis (PVE) is a serious disease affecting ~0.4% of prosthetic valve recipients per year. F-FDG-PET/CT has high sensitivity and specificity for PVE and is included as major criterion for the diagnosis in recent guidelines of the European Society of Cardiology. We addressed the question whether increased FDG-uptake in mediastinal lymph nodes could help to support the visual diagnostic assessment of PVE. In this sub-analysis of a previously published retrospective multicentre study, 160 unique patients were identified who underwent F-FDG-PET/CT for evaluation of suspected PVE. F-FDG-PET/CT was performed in adherence to the European Association of Nuclear Medicine guidelines of 2015 and scans were assessed for signs of mediastinal lymph node activity by 2 experienced nuclear medicine physicians who were blinded to clinical context. Clinical diagnosis of PVE had been established based on surgical findings or multidisciplinary consensus after a 1-year follow-up in 80 of 160 patients (50%). In total, 52 patients showed increased mediastinal lymph node activity. Mediastinal lymph node activity on F-FDG-PET/CT did not increase diagnostic accuracy when added to the visual analysis of scans for signs of PVE: : 0.118, = 0.731). After excluding patients with known confounders for F-FDG-PET/CT, namely use of Bioglue® during prosthetic valve implantation and C-reactive protein levels below 40 mg/L, mediastinal lymph node activity was still not of additional diagnostic value compared to visual analysis alone (X:0.129, = 0.723). Assessment of mediastinal lymph node activity did not improve F-FDG-PET/CT diagnostic accuracy for suspected PVE compared to visual assessment of the valve alone, as it seems to be a rather a specific finding, that might be caused by sternal wound or mediastinal infections or even by subclinical respiratory infections. Future studies might elucidate whether increased FDG active lymph nodes indicate a high-risk patient group and whether more detailed assessment of mediastinal lymph nodes could improve their additional diagnostic benefit.
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http://dx.doi.org/10.3389/fcvm.2021.717774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385671PMC
August 2021

Limitations and Pitfalls of FDG-PET/CT in Infection and Inflammation.

Semin Nucl Med 2021 Jul 7. Epub 2021 Jul 7.

Department of Nuclear Medicine & PET Center, Aarhus University Hospital, Aarhus N. Electronic address:

White blood cells activated by either a pathogen or as part of a systemic inflammatory disease are characterized by high energy consumption and are therefore taking up the glucose analogue PET tracer FDG avidly. It is therefore not surprising that a steadily growing body of research and clinical reports now supports the use of FDG PET/CT to diagnose a wide range of patients with non-oncological diseases. However, using FDG PET/CT in patients with infectious or inflammatory diseases has some limitations and potential pitfalls that are not necessarily as pronounced in oncology FDG PET/CT. Some of these limitations are of a general nature and related to the laborious acquisition of PET images in patients that are often acutely ill, whereas others are more disease-specific and related to the particular metabolism in some of the organs most commonly affected by infections or inflammatory disease. Both inflammatory and infectious diseases are characterized by a more diffuse and less pathognomonic pattern of FDG uptake than oncology FDG PET/CT and the affected organs also typically have some physiological FDG uptake. In addition, patients referred to PET/CT with suspected infection or inflammation are rarely treatment naïve and may have received varying doses of antibiotics, corticosteroids or other immune-modulating drugs at the time of their examination. Combined, this results in a higher rate of false positive FDG findings and also in some cases a lower sensitivity to detect active disease. In this review, we therefore discuss the limitations and pitfalls of FDG PET/CT to diagnose infections and inflammation taking these issues into consideration. Our review encompasses the most commonly encountered inflammatory and infectious diseases in head and neck, in the cardiovascular system, in the abdominal organs and in the musculoskeletal system. Finally, new developments in the field of PET/CT that may help overcome some of these limitations are briefly highlighted.
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http://dx.doi.org/10.1053/j.semnuclmed.2021.06.008DOI Listing
July 2021

Long axial field of view PET scanners: a road map to implementation and new possibilities.

Eur J Nucl Med Mol Imaging 2021 Jun 16. Epub 2021 Jun 16.

Medical Imaging Center, Department of Nuclear Medicine and Molecular, University of Groningen, University Medical Center Groningen, Hanzeplein 1, PO 9700 RB, Groningen, The Netherlands.

In this contribution, several opportunities and challenges for long axial field of view (LAFOV) PET are described. It is an anthology in which the main issues have been highlighted. A consolidated overview of the camera system implementation, business and financial plan, opportunities and challenges is provided. What the nuclear medicine and molecular imaging community can expect from these new PET/CT scanners is the delivery of more comprehensive information to the clinicians for advancing diagnosis, therapy evaluation and clinical research.
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http://dx.doi.org/10.1007/s00259-021-05461-6DOI Listing
June 2021

Comparison and validation of FDG-PET/CT scores for polymyalgia rheumatica.

Rheumatology (Oxford) 2021 Jun 12. Epub 2021 Jun 12.

Medical Imaging Center, Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Objectives: To compare and validate the diagnostic accuracy of FDG-PET/CT scores for polymyalgia rheumatica (PMR); and to explore their relationship with clinical factors.

Methods: This retrospective study included 39 consecutive patients diagnosed with PMR and 19 PMR comparators. The final clinical diagnosis was established after 6 months follow-up. Patients underwent FDG-PET/CT prior to glucocorticoid treatment. Visual grading of FDG uptake was performed at 30 anatomic sites. Three FDG-PET/CT scores (one by Henckaerts, two by Sondag) and two algorithms (by Flaus and Owen) were investigated. Receiver operating characteristic (ROC) analysis with area under the curve (AUC) was performed. Diagnostic accuracy was assessed at predefined cut-off points.

Results: All three FDG-PET/CT scores showed high diagnostic accuracy for a clinical diagnosis of PMR in the ROC analysis (AUC 0.889 to 0.914). The Henckaerts Score provided a sensitivity of 89.7% and specificity of 84.2% at its predefined cut-off point. A simplified Henckaerts Score showed similar diagnostic accuracy as the original score. The Sondag Scores showed limited specificity at their predefined cut-off points (i.e. 47.4% and 63.2%), while ROC analysis suggested that substantially higher cut-off points are needed for these scores. The Owen and Flaus Algorithms demonstrated high sensitivity, but lower specificity (i.e. 78.9% and 42.1%, respectively) for PMR. Female sex and presence of large vessel vasculitis were associated with lower FDG-PET/CT scores in patients with PMR.

Conclusion: The Henckaerts Score showed the highest diagnostic utility for PMR. A modified, concise version of the Henckaerts Score provided similar diagnostic accuracy as the original score.
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http://dx.doi.org/10.1093/rheumatology/keab483DOI Listing
June 2021

Interleukin-2 PET imaging in patients with metastatic melanoma before and during immune checkpoint inhibitor therapy.

Eur J Nucl Med Mol Imaging 2021 Jun 2. Epub 2021 Jun 2.

Department of Medical Oncology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands.

Purpose: Immune checkpoint inhibitors can induce a T cell-mediated anti-tumor immune response in patients with melanoma. Visualizing T cell activity using positron emission tomography (PET) might allow early insight into treatment efficacy. Activated tumor-infiltrating T cells express the high-affinity interleukin-2 receptor (IL-2R). Therefore, we performed a pilot study, using fluorine-18-labeled IL-2 ([F]FB-IL2 PET), to evaluate whether a treatment-induced immune response can be detected.

Methods: Patients with metastatic melanoma received ~ 200 MBq [F]FB-IL2 intravenously, followed by a PET/CT scan before and during immune checkpoint inhibitor therapy. [F]FB-IL2 uptake was measured as standardized uptake value in healthy tissues (SUV) and tumor lesions (SUV). Response to therapy was assessed using RECIST v1.1. Archival tumor tissues were used for immunohistochemical analyses of T cell infiltration.

Results: Baseline [F]FB-IL2 PET scans were performed in 13 patients. SUV at baseline was highest in the kidneys (14.2, IQR: 11.6-18.0) and liver (10.6, IQR: 8.6-13.4). In lymphoid tissues, uptake was highest in spleen (10.9, IQR: 8.8-12.4) and bone marrow (2.5, IQR: 2.1-3.0). SUV in tumor lesions (n = 41) at baseline was 1.9 (IQR: 1.7-2.3). In 11 patients, serial imaging was performed, three at week 6, seven at week 2, and one at week 4. Median [F]FB-IL2 tumor uptake decreased from 1.8 (IQR: 1.7-2.1) at baseline to 1.7 (IQR: 1.4-2.1) during treatment (p = 0.043). Changes in [F]FB-IL2 tumor uptake did not correlate with response. IL-2R expression in four archival tumor tissues was low and did not correlate with baseline [F]FB-IL2 uptake. No [F]FB-IL2-related side effects occurred.

Conclusion: PET imaging of the IL-2R, using [F]FB-IL2, is safe and feasible. In this small patient group, serial [F]FB-IL2-PET imaging did not detect a treatment-related immune response.

Trial Registration: Clinicaltrials.gov : NCT02922283; EudraCT: 2014-003387.20.
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http://dx.doi.org/10.1007/s00259-021-05407-yDOI Listing
June 2021

Radionuclide Imaging of Fungal Infections and Correlation with the Host Defense Response.

J Fungi (Basel) 2021 May 22;7(6). Epub 2021 May 22.

Medical Imaging Center, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.

The human response to invading fungi includes a series of events that detect, kill, or clear the fungi. If the metabolic host response is unable to eliminate the fungi, an infection ensues. Some of the host response's metabolic events to fungi can be imaged with molecules labelled with radionuclides. Several important clinical applications have been found with radiolabelled biomolecules of inflammation. F-fluorodeoxyglucose is the tracer that has been most widely investigated in the host defence of fungi. This tracer has added value in the early detection of infection, in staging and visualising dissemination of infection, and in monitoring antifungal treatment. Radiolabelled antimicrobial peptides showed promising results, but large prospective studies in fungal infection are lacking. Other tracers have also been used in imaging events of the host response, such as the migration of white blood cells at sites of infection, nutritional immunity in iron metabolism, and radiolabelled monoclonal antibodies. Many tracers are still at the preclinical stage. Some tracers require further studies before translation into clinical use. The application of therapeutic radionuclides offers a very promising clinical application of these tracers in managing drug-resistant fungi.
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http://dx.doi.org/10.3390/jof7060407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224611PMC
May 2021

Value of F-FES PET in Solving Clinical Dilemmas in Breast Cancer Patients: A Retrospective Study.

J Nucl Med 2021 Sep 14;62(9):1214-1220. Epub 2021 May 14.

Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; and

Breast cancer (BC) is a heterogeneous disease in which estrogen receptor (ER) expression plays an important role in most tumors. A clinical dilemma may arise when a metastasis biopsy to determine the ER status cannot be performed safely or when ER heterogeneity is suspected between tumor lesions. Whole-body ER imaging, such as 16α-F-fluoro-17β-estradiol (F-FES) PET, may have added value in these situations. However, the role of this imaging technique in routine clinical practice remains to be further determined. Therefore, we assessed whether the physician's remaining clinical dilemma after the standard workup was solved by the F-FES PET scan. This retrospective study included F-FES PET scans of patients who had (or were suspected to have) ER-positive metastatic BC and for whom a clinical dilemma remained after the standard workup. The scans were performed at the University Medical Center of Groningen between November 2009 and January 2019. We investigated whether the physician's clinical dilemma was solved, defined either as solving the clinical dilemma through the F-FES PET results or as basing a treatment decision directly on the F-FES PET results. In addition, the category of the clinical dilemma was reported, as well as the rate of F-FES-positive or -negative PET scans, and any correlation to the frequency of solved dilemmas was determined. One hundred F-FES PET scans were performed on 83 patients. The clinical dilemma categories were inability to determine the extent of metastatic disease or suspected metastatic disease with the standard workup ( = 52), unclear ER status of the tumor ( = 31), and inability to determine which primary tumor caused the metastases ( = 17). The dilemmas were solved by F-FES PET in 87 of 100 scans (87%). In 81 of 87 scans, a treatment decision was based directly on F-FES PET results (treatment change, 51 scans; continuance, 30 scans). The frequency of solved dilemmas was not related to the clinical dilemma category ( = 0.334). However, the frequency of solved dilemmas was related to whether scans were F-FES-positive ( = 63) or F-FES-negative ( = 37; < 0.001). For various indications, the F-FES PET scan can help to solve most clinical dilemmas that may remain after the standard workup. Therefore, the F-FES PET scan has added value in BC patients who present the physician with a clinical dilemma.
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http://dx.doi.org/10.2967/jnumed.120.256826DOI Listing
September 2021

Therapy response evaluation in large-vessel vasculitis: a new role for [18F]FDG-PET/CT?

Rheumatology (Oxford) 2021 08;60(8):3494-3495

Vasculitis Expertise Centre Groningen, University of Groningen, Groningen, the Netherlands.

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http://dx.doi.org/10.1093/rheumatology/keab375DOI Listing
August 2021

Position paper of the EACVI and EANM on artificial intelligence applications in multimodality cardiovascular imaging using SPECT/CT, PET/CT, and cardiac CT.

Eur J Nucl Med Mol Imaging 2021 05 17;48(5):1399-1413. Epub 2021 Apr 17.

Turku PET Centre, Turku University Hospital, University of Turku, Turku, Finland.

In daily clinical practice, clinicians integrate available data to ascertain the diagnostic and prognostic probability of a disease or clinical outcome for their patients. For patients with suspected or known cardiovascular disease, several anatomical and functional imaging techniques are commonly performed to aid this endeavor, including coronary computed tomography angiography (CCTA) and nuclear cardiology imaging. Continuous improvement in positron emission tomography (PET), single-photon emission computed tomography (SPECT), and CT hardware and software has resulted in improved diagnostic performance and wide implementation of these imaging techniques in daily clinical practice. However, the human ability to interpret, quantify, and integrate these data sets is limited. The identification of novel markers and application of machine learning (ML) algorithms, including deep learning (DL) to cardiovascular imaging techniques will further improve diagnosis and prognostication for patients with cardiovascular diseases. The goal of this position paper of the European Association of Nuclear Medicine (EANM) and the European Association of Cardiovascular Imaging (EACVI) is to provide an overview of the general concepts behind modern machine learning-based artificial intelligence, highlights currently prefered methods, practices, and computational models, and proposes new strategies to support the clinical application of ML in the field of cardiovascular imaging using nuclear cardiology (hybrid) and CT techniques.
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http://dx.doi.org/10.1007/s00259-021-05341-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113178PMC
May 2021

FDG-PET/CT in intensive care patients with bloodstream infection.

Crit Care 2021 04 7;25(1):133. Epub 2021 Apr 7.

Department of Critical Care, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Background: 2-Deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) is an advanced imaging technique that can be used to examine the whole body for an infection focus in a single examination in patients with bloodstream infection (BSI) of unknown origin. However, literature on the use of this technique in intensive care patients is scarce. The purpose of this study was to evaluate the diagnostic yield of FDG-PET/CT in intensive care patients with BSI.

Methods: In this retrospective cohort study, all intensive care patients from our Dutch university medical center who had culture-proven BSI between 2010 and 2020 and underwent FDG-PET/CT to find the focus of infection were included. Diagnostic performance was calculated and logistic regression analysis was performed to evaluate the association between FDG-PET/CT outcome and C-reactive protein level (CRP), leukocyte count, duration of antibiotic treatment, duration of ICU stay, quality of FDG-PET/CT, and dependency on mechanical ventilation. In addition, the impact of FDG-PET/CT on clinical treatment was evaluated.

Results: 30 intensive care patients with BSI were included. In 21 patients, an infection focus was found on FDG-PET/CT which led to changes in clinical management in 14 patients. FDG-PET/CT achieved a sensitivity of 90.9% and specificity of 87.5% for identifying the focus of infection. Poor quality of the FDG-PET images significantly decreased the likelihood of finding an infection focus as compared to reasonable or good image quality (OR 0.16, P = 0.034). No other variables were significantly associated with FDG-PET/CT outcome. No adverse events during the FDG-PET/CT procedure were reported.

Conclusion: FDG-PET/CT has a high diagnostic yield for detecting the infection focus in patients with BSI admitted to intensive care. Poor PET image quality was significantly associated with a decreased likelihood of finding the infection focus in patients with BSI. This could be improved by adequate dietary preparation and cessation of intravenous glucose and glucose-regulating drugs. Recent advances in PET/CT technology enable higher image quality with shorter imaging time and may contribute to routinely performing FDG-PET/CT in intensive care patients with BSI of unknown origin.
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http://dx.doi.org/10.1186/s13054-021-03557-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8028784PMC
April 2021

A Review on the Value of Imaging in Differentiating between Large Vessel Vasculitis and Atherosclerosis.

J Pers Med 2021 Mar 23;11(3). Epub 2021 Mar 23.

Department of Nuclear Medicine and Molecular Imaging, Medical Imaging Center, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands.

Imaging is becoming increasingly important for the diagnosis of large vessel vasculitis (LVV). Atherosclerosis may be difficult to distinguish from LVV on imaging as both are inflammatory conditions of the arterial wall. Differentiating atherosclerosis from LVV is important to enable optimal diagnosis, risk assessment, and tailored treatment at a patient level. This paper reviews the current evidence of ultrasound (US), 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (FDG-PET), computed tomography (CT), and magnetic resonance imaging (MRI) to distinguish LVV from atherosclerosis. In this review, we identified a total of eight studies comparing LVV patients to atherosclerosis patients using imaging-four US studies, two FDG-PET studies, and two CT studies. The included studies mostly applied different methodologies and outcome parameters to investigate vessel wall inflammation. This review reports the currently available evidence and provides recommendations on further methodological standardization methods and future directions for research.
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http://dx.doi.org/10.3390/jpm11030236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005013PMC
March 2021

Study on intracranial meningioma using PET ligand investigation during follow-up over years (SIMPLIFY).

Neuroradiology 2021 Mar 10. Epub 2021 Mar 10.

Department of Neurosurgery, University of Groningen, University Medical Center Groningen, Hanzeplein 1, P.O. Box 30.001, 9700RB, Groningen, the Netherlands.

Purpose: Radiologic follow-up of patients with a meningioma at the skull base or near the venous sinuses with magnetic resonance imaging (MRI) after stereotactic radiotherapy (SRT) and neurosurgical resection(s) can be difficult to interpret. This study evaluates the addition of C-methionine positron emission tomography (MET-PET) to the regular MRI follow-up.

Methods: This prospective pilot study included patients with predominantly WHO grade I meningiomas at the skull base or near large vascular structures. Previous SRT was part of their oncological treatment. A MET-PET in adjunct to their regular MRI follow-up was performed. The standardized uptake value (SUV) was determined for the tumor and the healthy brain, on the pre-SRT target delineation MET-PET and the follow-up MET-PET. Tumor-to-normal ratios were calculated, and C-methionine uptake over time was analyzed. Agreement between the combined MRI/MET-PET report and the MRI-only report was determined using Cohen's κ.

Results: Twenty patients with stable disease underwent an additional MET-PET, with a median follow-up of 84 months after SRT. Post-SRT SUV T/N ratios ranged between 2.16 and 3.17. When comparing the pre-SRT and the post-SRT MET-PET, five categories of SUV T/N ratios did not change significantly. Only the SUV T/N decreased significantly from 2.57 (SD 1.02) to 2.20 (SD 0.87) [p = 0.004]. A κ of 0.77 was found, when comparing the MRI/MET-PET report to the MRI-only report, indicating no major change in interpretation of follow-up data.

Conclusion: In this pilot study, C-methionine uptake remained remarkably high in meningiomas with long-term follow-up after SRT. Adding MET-PET to the regular MRI follow-up had no impact on the interpretation of follow-up imaging.
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http://dx.doi.org/10.1007/s00234-021-02683-1DOI Listing
March 2021

PET/CT Imaging for Personalized Management of Infectious Diseases.

J Pers Med 2021 Feb 16;11(2). Epub 2021 Feb 16.

Departments of Radiology, Nuclear Medicine and Molecular Imaging, University of Groningen, 9700 RB Groningen, The Netherlands.

Positron emission tomography combined with computed tomography (PET/CT) is a nuclear imaging technique which is increasingly being used in infectious diseases. Because infection foci often consume more glucose than surrounding tissue, most infections can be diagnosed with PET/CT using 2-deoxy-2-[18F]fluoro-D-glucose (FDG), an analogue of glucose labeled with Fluorine-18. In this review, we discuss common infectious diseases in which FDG-PET/CT is currently applied including bloodstream infection of unknown origin, infective endocarditis, vascular graft infection, spondylodiscitis, and cyst infections. Next, we highlight the latest developments within the field of PET/CT, including total body PET/CT, use of novel PET radiotracers, and potential future applications of PET/CT that will likely lead to increased capabilities for patient-tailored treatment of infectious diseases.
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http://dx.doi.org/10.3390/jpm11020133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920259PMC
February 2021

An international expert opinion statement on the utility of PET/MR for imaging of skeletal metastases.

Eur J Nucl Med Mol Imaging 2021 05 22;48(5):1522-1537. Epub 2021 Feb 22.

Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, USA.

Background: MR is an important imaging modality for evaluating musculoskeletal malignancies owing to its high soft tissue contrast and its ability to acquire multiparametric information. PET provides quantitative molecular and physiologic information and is a critical tool in the diagnosis and staging of several malignancies. PET/MR, which can take advantage of its constituent modalities, is uniquely suited for evaluating skeletal metastases. We reviewed the current evidence of PET/MR in assessing for skeletal metastases and provided recommendations for its use.

Methods: We searched for the peer reviewed literature related to the usage of PET/MR in the settings of osseous metastases. In addition, expert opinions, practices, and protocols of major research institutions performing research on PET/MR of skeletal metastases were considered.

Results: Peer-reviewed published literature was included. Nuclear medicine and radiology experts, including those from 13 major PET/MR centers, shared the gained expertise on PET/MR use for evaluating skeletal metastases and contributed to a consensus expert opinion statement. [18F]-FDG and non [18F]-FDG PET/MR may provide key advantages over PET/CT in the evaluation for osseous metastases in several primary malignancies.

Conclusion: PET/MR should be considered for staging of malignancies where there is a high likelihood of osseous metastatic disease based on the characteristics of the primary malignancy, hight clinical suspicious and in case, where the presence of osseous metastases will have an impact on patient management. Appropriate choice of tumor-specific radiopharmaceuticals, as well as stringent adherence to PET and MR protocols, should be employed.
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http://dx.doi.org/10.1007/s00259-021-05198-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240455PMC
May 2021

The Added Value of [F]FDG PET/CT in the Management of Invasive Fungal Infections.

Diagnostics (Basel) 2021 Jan 17;11(1). Epub 2021 Jan 17.

Medical Imaging Center, University of Groningen, University Medical Center Groningen, 9700 AC Groningen, The Netherlands.

Anatomy-based imaging methods are the usual imaging methods used in assessing invasive fungal infections (IFIs). [F]FDG PET/CT has also been used in the evaluation of IFIs. We assessed the added value of [F]FDG PET/CT when added to the most frequently used anatomy-based studies in the evaluation of IFIs. The study was conducted in two University Medical Centers in the Netherlands. Reports of [F]FDG PET/CT and anatomy-based imaging performed within two weeks of the [F]FDG PET/CT scan were retrieved, and the presence and sites of IFI lesions were documented for each procedure. We included 155 [F]FDG PET/CT scans performed in 73 patients. A total of 216 anatomy-based studies including 80 chest X-rays, 89 computed tomography studies, 14 magnetic resonance imaging studies, and 33 ultrasound imaging studies were studied. The anatomy-based studies were concordant with the [F]FDG PET/CT for 94.4% of the scans performed. [F]FDG PET/CT detected IFI lesions outside of the areas imaged by the anatomy-based studies in 48.6% of the scans. In 74% of the patients, [F]FDG PET/CT added value in the management of the IFIs.
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http://dx.doi.org/10.3390/diagnostics11010137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830875PMC
January 2021

Serial [F]-FDHT-PET to predict bicalutamide efficacy in patients with androgen receptor positive metastatic breast cancer.

Eur J Cancer 2021 02 18;144:151-161. Epub 2020 Dec 18.

Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. Electronic address:

Background: The androgen receptor (AR) is a potential target in metastatic breast cancer (MBC), and 16β-[F]-fluoro-5α-dihydrotestosterone positron emission tomography ([F]-FDHT-PET) can be used for noninvasive visualisation of AR. [F]-FDHT uptake reduction during AR-targeting therapy reflects AR occupancy and might be predictive for treatment response. We assessed the feasibility of [F]-FDHT-PET to detect changes in AR availability during bicalutamide treatment and correlated these changes with treatment response.

Patients And Methods: Patients with AR + MBC, regardless of oestrogen receptor status, received an [F]-FDHT-PET at baseline and after 4-6 weeks bicalutamide treatment. Baseline [F]-FDHT uptake was expressed as maximum standardised uptake value. Percentage change in tracer uptake, corrected for background activity (SUV), between baseline and follow-up PET scan (% reduction), was assessed per-patient and lesion. Clinical benefit was determined in accordance with Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 or clinical evaluation (absence of disease progression for ≥24 weeks).

Results: Baseline [F]-FDHT-PET in 21 patients detected 341 of 515 lesions found with standard imaging and 21 new lesions. Follow-up [F]-FDHT-PET was evaluable in 17 patients with 349 lesions, showing a decrease in median SUV from 1.3 to 0.7 per-patient and lesion (P < 0.001). Median % reduction per-patient was -45% and per-lesion -39%. In patients with progressive disease (n = 11), median % reduction was -30% versus -53% for patients who showed clinical benefit (in accordance with RECIST (n = 3) or clinical evaluation (n = 3); P = 0.338).

Conclusion: In this feasibility study, a bicalutamide-induced reduction in [F]-FDHT uptake could be detected by follow-up [F]-FDHT-PET in patients with AR + MBC. However, this change could not predict bicalutamide response.

Clinical Trial Information: NCT02697032.
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http://dx.doi.org/10.1016/j.ejca.2020.11.008DOI Listing
February 2021

Procedural recommendations of cardiac PET/CT imaging: standardization in inflammatory-, infective-, infiltrative-, and innervation- (4Is) related cardiovascular diseases: a joint collaboration of the EACVI and the EANM: summary.

Eur Heart J Cardiovasc Imaging 2020 12;21(12):1320-1330

Medical Imaging Centre, Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, The Netherlands.

With this summarized document we share the standard for positron emission tomography (PET)/(diagnostic)computed tomography (CT) imaging procedures in cardiovascular diseases that are inflammatory, infective, infiltrative, or associated with dysfunctional innervation (4Is) as recently published in the European Journal of Nuclear Medicine and Molecular Imaging. This standard should be applied in clinical practice and integrated in clinical (multicentre) trials for optimal standardization of the procedurals and interpretations. A major focus is put on procedures using [18F]-2-fluoro-2-deoxyglucose ([18F]FDG), but 4Is PET radiopharmaceuticals beyond [18F]FDG are also described in this summarized document. Whilst these novel tracers are currently mainly applied in early clinical trials, some multicentre trials are underway and we foresee in the near future their use in clinical care and inclusion in the clinical guidelines. Diagnosis and management of 4Is related cardiovascular diseases are generally complex and often require a multidisciplinary approach by a team of experts. The new standards described herein should be applied when using PET/CT and PET/magnetic resonance, within a multimodality imaging framework both in clinical practice and in clinical trials for 4Is cardiovascular indications.
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http://dx.doi.org/10.1093/ehjci/jeaa299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695243PMC
December 2020

Detection of Dural Metastases Before the Onset of Clinical Symptoms by 16α-[18F]Fluoro-17β-Estradiol PET in a Patient With Estrogen Receptor-Positive Breast Cancer.

Clin Nucl Med 2021 Mar;46(3):e165-e167

Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

Abstract: We offer an illustrative case about estrogen receptor (ER) imaging (also known as 16α-[18F]fluoro-17β-estradiol ([18F]-FES) PET) and the detection of metastatic lesions in the dural region. We present a case of a woman with ER-positive metastatic breast cancer and high [18F]-FES uptake in the dural region on PET imaging, without associated clinical symptoms. These lesions were missed on [18F]-FDG PET because of physiological [18F]-FDG uptake in the brain. This case highlighted some difficulties in the interpretation of imaging of brain metastases and demonstrated the added value of [18F]-FES PET imaging. [18F]-FES PET could be used to prove the presence of ER-positive metastases in the brain.
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http://dx.doi.org/10.1097/RLU.0000000000003382DOI Listing
March 2021

Procedural recommendations of cardiac PET/CT imaging: standardization in inflammatory-, infective-, infiltrative-, and innervation (4Is)-related cardiovascular diseases: a joint collaboration of the EACVI and the EANM.

Eur J Nucl Med Mol Imaging 2021 04 27;48(4):1016-1039. Epub 2020 Oct 27.

Medical Imaging Centre, Department of Nuclear Medicine & Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

With this document, we provide a standard for PET/(diagnostic) CT imaging procedures in cardiovascular diseases that are inflammatory, infective, infiltrative, or associated with dysfunctional innervation (4Is). This standard should be applied in clinical practice and integrated in clinical (multicenter) trials for optimal procedural standardization. A major focus is put on procedures using [F]FDG, but 4Is PET radiopharmaceuticals beyond [F]FDG are also described in this document. Whilst these novel tracers are currently mainly applied in early clinical trials, some multicenter trials are underway and we foresee in the near future their use in clinical care and inclusion in the clinical guidelines. Finally, PET/MR applications in 4Is cardiovascular diseases are also briefly described. Diagnosis and management of 4Is-related cardiovascular diseases are generally complex and often require a multidisciplinary approach by a team of experts. The new standards described herein should be applied when using PET/CT and PET/MR, within a multimodality imaging framework both in clinical practice and in clinical trials for 4Is cardiovascular indications.
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http://dx.doi.org/10.1007/s00259-020-05066-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041672PMC
April 2021
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