Publications by authors named "Erik H Aarntzen"

58 Publications

In Vivo PET Imaging of Monocytes Labeled with [Zr]Zr-PLGA-NH Nanoparticles in Tumor and Infection Models.

Cancers (Basel) 2021 Oct 10;13(20). Epub 2021 Oct 10.

Department of Medical Imaging, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands.

The exponential growth of research on cell-based therapy is in major need of reliable and sensitive tracking of a small number of therapeutic cells to improve our understanding of the in vivo cell-targeting properties. In-labeled poly(lactic--glycolic acid) with a primary amine endcap nanoparticles ([In]In-PLGA-NH NPs) were previously used for cell labeling and in vivo tracking, using SPECT/CT imaging. However, to detect a low number of cells, a higher sensitivity of PET is preferred. Therefore, we developed Zr-labeled NPs for ex vivo cell labeling and in vivo cell tracking, using PET/MRI. We intrinsically and efficiently labeled PLGA-NH NPs with [Zr]ZrCl. In vitro, [Zr]Zr-PLGA-NH NPs retained the radionuclide over a period of 2 weeks in PBS and human serum. THP-1 (human monocyte cell line) cells could be labeled with the NPs and retained the radionuclide over a period of 2 days, with no negative effect on cell viability (specific activity 279 ± 10 kBq/10 cells). PET/MRI imaging could detect low numbers of [Zr]Zr-THP-1 cells (10,000 and 100,000 cells) injected subcutaneously in Matrigel. Last, in vivo tracking of the [Zr]Zr-THP-1 cells upon intravenous injection showed specific accumulation in local intramuscular infection and infiltration into MDA-MB-231 tumors. In conclusion, we showed that [Zr]Zr-PLGA-NH NPs can be used for immune-cell labeling and subsequent in vivo tracking of a small number of cells in different disease models.
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http://dx.doi.org/10.3390/cancers13205069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533969PMC
October 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

An Explorative Study on Monocyte Reprogramming in the Context of Periodontitis and .

Front Immunol 2021 13;12:695227. Epub 2021 Aug 13.

Department of Internal Medicine and Radboud Institute for Molecular Life Science (RIMLS), Radboud University Medical Center, Nijmegen, Netherlands.

Aims: Periodontitis is an independent risk factor for cardiovascular disease, but the mechanistic link is not fully understood. In atherosclerotic cardiovascular disease, monocytes can adopt a persistent hyperresponsive phenotype, termed trained immunity. We hypothesized that periodontitis-associated bacteria can induce trained immunity in monocytes, which subsequently accelerate atherosclerosis development.

Materials And Methods: We combined experiments on human primary monocytes and techniques in patients with periodontitis to test this hypothesis. Adherent peripheral blood mononuclear cells (PBMCs) were transiently exposed to for 24 hours, and restimulated with lipopolysaccharide (LPS) or Pam3CysK4 (P3C) six days later, to measure interleukin-6 (IL-6) and tumor necrosis factor α (TNFα) production. In an exploratory observational study, patients with severe periodontitis (63 ± 6 years, n=14) and control subjects with no-to-mild periodontitis (54 ± 10 years, n=14) underwent venipuncture and 2'-deoxy-2'-[F]fluoro-D-glucose positron-emission-tomography ([F]FDG PET/CT) scanning.

Results: When adherent peripheral blood mononuclear cells (PBMCs) were transiently exposed to for 24 hours, and restimulated with LPS or P3C six days later, IL-6 and TNFα production was significantly increased (TNFα/P3C, p<0.01). Circulating leukocytes, IL-6 and interleukin-1 receptor antagonist (IL-1Ra) concentrations were generally higher in patients compared to controls (leukocytes: p<0.01; IL-6: p=0.08; IL-1Ra: p=0.10). Cytokine production capacity in PBMCs after 24h stimulation revealed no differences between groups. [F]FDG PET/CT imaging showed a trend for increased [F]FDG-uptake in the periodontium [mean standard uptake value (SUV), p=0.11] and in femur bone marrow (SUV, p=0.06), but no differences were observed for vascular inflammation. Positive correlations between severity of periodontitis, measured by The Dutch Periodontal Screening Index and pocket depth, with circulating inflammatory markers and tissue inflammation were found.

Conclusions: induces long-term activation of human monocytes (trained immunity). Patients with severe periodontitis did have signs of increased systemic inflammation and hematopoietic tissue activation. However, their circulating monocytes did not show a hyperresponsive phenotype. Together we suggest that trained immunity might contribute to local periodontal inflammation which warrants further investigation.
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http://dx.doi.org/10.3389/fimmu.2021.695227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414567PMC
August 2021

The Influence of the Exclusion of Central Necrosis on [F]FDG PET Radiomic Analysis.

Diagnostics (Basel) 2021 Jul 19;11(7). Epub 2021 Jul 19.

Section of Nuclear Medicine, Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.

Background: Central necrosis can be detected on [F]FDG PET/CT as a region with little to no tracer uptake. Currently, there is no consensus regarding the inclusion of regions of central necrosis during volume of interest (VOI) delineation for radiomic analysis. The aim of this study was to assess how central necrosis affects radiomic analysis in PET.

Methods: Forty-three patients, either with non-small cell lung carcinomas (NSCLC, = 12) or with pheochromocytomas or paragangliomas (PPGL, = 31), were included retrospectively. VOIs were delineated with and without central necrosis. From all VOIs, 105 radiomic features were extracted. Differences in radiomic features between delineation methods were assessed using a paired -test with Benjamini-Hochberg multiple testing correction. In the PPGL cohort, performances of the radiomic models to predict the noradrenergic biochemical profile were assessed by comparing the areas under the receiver operating characteristic curve (AUC) for both delineation methods.

Results: At least 65% of the features showed significant differences between VOI and VOI (65%, 79% and 82% for the NSCLC, PPGL and combined cohort, respectively). The AUCs of the radiomic models were not significantly different between delineation methods.

Conclusion: In both tumour types, almost two-third of the features were affected, demonstrating that the impact of whether or not to include central necrosis in the VOI on the radiomic feature values is significant. Nevertheless, predictive performances of both delineation methods were comparable. We recommend that radiomic studies should report whether or not central necrosis was included during delineation.
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http://dx.doi.org/10.3390/diagnostics11071296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8304274PMC
July 2021

Characterization of Intrinsically Radiolabeled Poly(lactic--glycolic acid) Nanoparticles for ex Vivo Autologous Cell Labeling and in Vivo Tracking.

Bioconjug Chem 2021 08 23;32(8):1802-1811. Epub 2021 Jun 23.

Department of Medical Imaging, Radboud Institute for Molecular Life Sciences, Radboud university Medical Center, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands.

With the advent of novel immunotherapies, interest in ex vivo autologous cell labeling for in vivo cell tracking has revived. However, current clinically available labeling strategies have several drawbacks, such as release of radiolabel over time and cytotoxicity. Poly(lactic--glycolic acid) nanoparticles (PLGA NPs) are clinically used biodegradable carriers of contrast agents, with high loading capacity for multimodal imaging agents. Here we show the development of PLGA-based NPs for ex vivo cell labeling and in vivo cell tracking with SPECT. We used primary amine-modified PLGA polymers (PLGA-NH) to construct NPs similar to unmodified PLGA NPs. PLGA-NH NPs were efficiently radiolabeled without chelator and retained the radionuclide for 2 weeks. Monocyte-derived dendritic cells labeled with [In]In-PLGA-NH showed higher specific activity than those labeled with [In]In-oxine, with no negative effect on cell viability. SPECT/CT imaging showed that radiolabeled THP-1 cells accumulated at the infection site in mice. In conclusion, PLGA-NH NPs are able to retain In, independent of chelator presence. Furthermore, [In]In-PLGA-NH allows cell labeling with high specific activity and no loss of activity over prolonged time intervals. Finally, in vivo tracking of ex vivo labeled THP-1 cells was demonstrated in an infection model using SPECT/CT imaging.
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http://dx.doi.org/10.1021/acs.bioconjchem.1c00271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377710PMC
August 2021

Intravenous to Oral Switch in Complicated Staphylococcus aureus Bacteremia Without Endovascular Infection: A Retrospective Single-Center Cohort Study.

Clin Infect Dis 2021 09;73(5):895-898

Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.

In this retrospective cohort study, selected patients with disseminated Staphylococcus aureus bacteremia, but without endovascular infection on echocardiography and 18F-FDG-PET/CT, were free of relapse after IV-oral switch. Mortality was low and similar to patients who received prolonged intravenous treatment. IV-oral switch was associated with a shorter length of hospital stay.
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http://dx.doi.org/10.1093/cid/ciab156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423458PMC
September 2021

Autologous monocyte-derived DC vaccination combined with cisplatin in stage III and IV melanoma patients: a prospective, randomized phase 2 trial.

Cancer Immunol Immunother 2020 Mar 24;69(3):477-488. Epub 2020 Jan 24.

Department of Medical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands.

Background: Autologous dendritic cell (DC) vaccines can induce tumor-specific T cells, but their effect can be counteracted by immunosuppressive mechanisms. Cisplatin has shown immunomodulatory effects in vivo which may enhance efficacy of DC vaccination.

Methods: This is a prospective, randomized, open-label phase 2 study (NCT02285413) including stage III and IV melanoma patients receiving 3 biweekly vaccinations of gp100 and tyrosinase mRNA-loaded monocyte-derived DCs with or without cisplatin. Primary objectives were to study immunogenicity and feasibility, and secondary objectives were to assess toxicity and survival.

Results: Twenty-two stage III and 32 stage IV melanoma patients were analyzed. Antigen-specific CD8 T cells were found in 44% versus 67% and functional T cell responses in 28% versus 19% of skin-test infiltrating lymphocytes in patients receiving DC vaccination with and without cisplatin, respectively. Four patients stopped cisplatin because of toxicity and continued DC monotherapy. No therapy-related grade 3 or 4 adverse events occurred due to DC monotherapy. During combination therapy, one therapy-related grade 3 adverse event, decompensated heart failure due to fluid overload, occurred. The clinical outcome parameters did not clearly suggest significant differences.

Conclusions: Combination of DC vaccination and cisplatin in melanoma patients is feasible and safe, but does not seem to result in more tumor-specific T cell responses or improved clinical outcome, when compared to DC vaccination monotherapy.
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http://dx.doi.org/10.1007/s00262-019-02466-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044256PMC
March 2020

Arterial Wall Inflammation and Increased Hematopoietic Activity in Patients With Primary Aldosteronism.

J Clin Endocrinol Metab 2020 05;105(5)

Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.

Context: Primary aldosteronism (PA) confers an increased risk of cardiovascular disease (CVD), independent of blood pressure. Animal models have shown that aldosterone accelerates atherosclerosis through proinflammatory changes in innate immune cells; human data are scarce.

Objective: The objective of this article is to explore whether patients with PA have increased arterial wall inflammation, systemic inflammation, and reprogramming of monocytes.

Design: A cross-sectional cohort study compared vascular inflammation on 2'-deoxy-2'-(18F)fluoro-D-glucose; (18F-FDG) positron emission tomography-computed tomography, systemic inflammation, and monocyte phenotypes and transcriptome between PA patients and controls.

Setting: This study took place at Radboudumc and Rijnstate Hospital, the Netherlands.

Patients: Fifteen patients with PA and 15 age-, sex-, and blood pressure-matched controls with essential hypertension (EHT) participated.

Main Outcome Measures And Results: PA patients displayed a higher arterial 18F-FDG uptake in the descending and abdominal aorta (P < .01, P < .05) and carotid and iliac arteries (both P < .01). In addition, bone marrow uptake was higher in PA patients (P < .05). Although PA patients had a higher monocyte-to-lymphocyte ratio (P < .05), systemic inflammatory markers, cytokine production capacity, and transcriptome of circulating monocytes did not differ. Monocyte-derived macrophages from PA patients expressed more TNFA; monocyte-derived macrophages of healthy donors cultured in PA serum displayed increased interleukin-6 and tumor necrosis factor-α production.

Conclusions: Because increased arterial wall inflammation is associated with accelerated atherogenesis and unstable plaques, this might importantly contribute to the increased CVD risk in PA patients. We did not observe inflammatory reprogramming of circulating monocytes. However, subtle inflammatory changes are present in the peripheral blood cell composition and monocyte transcriptome of PA patients, and in their monocyte-derived macrophages. Most likely, arterial inflammation in PA requires interaction between various cell types.
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http://dx.doi.org/10.1210/clinem/dgz306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105350PMC
May 2020

Programmed Cell Death-1/Ligand-1 PET Imaging: A Novel Tool to Optimize Immunotherapy?

PET Clin 2020 Jan 29;15(1):35-43. Epub 2019 Oct 29.

Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Postbus 9101, Nijmegen 6500 HB, the Netherlands. Electronic address:

Clinical indications for immune checkpoint inhibitor (ICI) therapy are rapidly expanding for various stages of several solid tumors. The success of ICIs results from a complex interplay between cancer cells and their immune microenvironment. PD-1/PD-L1 PET imaging enables to study of these interactions in the tumor microenvironment in a clinical setting. These noninvasive, sensitive and quantitative tools may play an important role in optimizing ICI efficacy.
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http://dx.doi.org/10.1016/j.cpet.2019.08.008DOI Listing
January 2020

Blood-derived dendritic cell vaccinations induce immune responses that correlate with clinical outcome in patients with chemo-naive castration-resistant prostate cancer.

J Immunother Cancer 2019 11 14;7(1):302. Epub 2019 Nov 14.

Department of Tumor Immunology and Medical Oncology, Radboud Institute for Molecular Life Sciences, Radboudumc, Geert Grooteplein 26, 6525 GA, Nijmegen, The Netherlands.

Background: Clinical benefit of cellular immunotherapy has been shown in patients with castration-resistant prostate cancer (CRPC). We investigated the immunological response and clinical outcome of vaccination with blood-derived CD1c myeloid dendritic cells (mDCs; cDC2) and plasmacytoid DCs (pDCs).

Methods: In this randomized phase IIa trial, 21 chemo-naive CRPC patients received maximally 9 vaccinations with mature mDCs, pDCs or a combination of mDCs plus pDCs. DCs were stimulated with protamine/mRNA and loaded with tumor-associated antigens NY-ESO-1, MAGE-C2 and MUC1. Primary endpoint was the immunological response after DC vaccination, which was monitored in peripheral blood and in T cell cultures of biopsies of post-treatment delayed-type hypersensitivity-skin tests. Main secondary endpoints were safety, feasibility, radiological PFS (rPFS) and overall survival. Radiological responses were assessed by MRIs and contrast-enhanced Ga-prostate-specific membrane antigen PET/CT, according to RECIST 1.1, PCWG2 criteria and immune-related response criteria.

Results: Both tetramer/dextramer-positive (dm) and IFN-γ-producing (IFN-γ) antigen specific T cells were detected more frequently in skin biopsies of patients with radiological non-progressive disease (5/13 patients; 38%) compared to patients with progressive disease (0/8 patients; 0%). In these patients with vaccination enhanced dm and IFN-γ antigen-specific T cells median rPFS was 18.8 months (n = 5) vs. 5.1 months (n = 16) in patients without IFN-γ-producing antigen-specific T cells (p = 0.02). The overall median rPFS was 9.5 months. All DC vaccines were well tolerated with grade 1-2 toxicity.

Conclusions: Immunotherapy with blood-derived DC subsets was feasible and safe and induced functional antigen-specific T cells. The presence of functional antigen-specific T cells correlated with an improved clinical outcome.

Trial Registration: ClinicalTrials.gov identifier NCT02692976, registered 26 February 2016, retrospectively registered.
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http://dx.doi.org/10.1186/s40425-019-0787-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854814PMC
November 2019

Imaging of T-cells and their responses during anti-cancer immunotherapy.

Theranostics 2019 10;9(25):7924-7947

Department of Radiology and Nuclear Medicine, Radboud university medical center, Nijmegen, The Netherlands.

Immunotherapy has proven to be an effective approach in a growing number of cancers. Despite durable clinical responses achieved with antibodies targeting immune checkpoint molecules, many patients do not respond. The common denominator for immunotherapies that have successfully been introduced in the clinic is their potential to induce or enhance infiltration of cytotoxic T-cells into the tumour. However, in clinical research the molecules, cells and processes involved in effective responses during immunotherapy remain largely obscure. Therefore, imaging technologies that interrogate T-cell responses in patients represent a powerful tool to boost further development of immunotherapy. This review comprises a comprehensive analysis of the imaging technologies that allow the characterisation of T-cell responses induced by anti-cancer immunotherapy, with emphasis on technologies that are clinically available or have high translational potential. Throughout we discuss their respective strengths and weaknesses, providing arguments for selecting the optimal imaging options for future research and patient management.
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http://dx.doi.org/10.7150/thno.37924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814447PMC
October 2019

18F-FDG PET/CT of Multiorgan Sarcoid-Like Reaction During Anti-PD-1 Treatment for Melanoma.

Clin Nucl Med 2019 Nov;44(11):905-906

Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.

We report a case of a 50-year-old woman treated with anti-PD-1 inhibition for metastatic melanoma. During treatment, extensive and transient histopathologically confirmed sarcoid-like reaction was detected in multiple organ systems and at different time points using F-FDG PET/CT imaging. Immune-related adverse events during anti-PD-1/PD-L1 antibody treatment are increasingly being reported. This case report emphasizes the broad spectrum of possible presentations of sarcoid-like reaction detected by F-FDG PET/CT and its evolution in time. For the clinician, awareness of these immune-related adverse events helps to accurately interpret findings on imaging.
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http://dx.doi.org/10.1097/RLU.0000000000002779DOI Listing
November 2019

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

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

Optimal respiratory-gated [F]FDG PET/CT significantly impacts the quantification of metabolic parameters and their correlation with overall survival in patients with pancreatic ductal adenocarcinoma.

EJNMMI Res 2019 Mar 13;9(1):24. Epub 2019 Mar 13.

Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Geert Grooteplein-Zuid 10, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.

Purpose: Metabolic parameters are increasingly being used to characterize tumors. Motion artifacts due to patient respiration introduce uncertainties in quantification of metabolic parameters during positron emission tomography (PET) image acquisition. The present study investigates the impact of amplitude-based optimal respiratory gating (ORG) on quantification of PET-derived image features in patients with pancreatic ductal adenocarcinoma (PDAC), in correlation with overall survival (OS).

Methods: Sixty-nine patients with histologically proven primary PDAC underwent 2'-deoxy-2'-[F]fluoroglucose ([F]FDG) PET/CT imaging during diagnostic work-up. Standard image acquisition and reconstruction was performed in accordance with the EANM guidelines and ORG images were reconstructed with a duty cycle of 35%. PET-derived image features, including standard parameters, first- and second-order texture features, were calculated from the standard and corresponding ORG images, and correlation with OS was assessed.

Results: ORG significantly impacts the quantification of nearly all features; values of single-voxel parameters (e.g., SUV) showed a wider range, volume-based parameters (e.g., SUV) were reduced, and texture features were significantly changed. After correction for motion artifacts using ORG, some features that describe intra-tumoral heterogeneity were more strongly correlated to OS.

Conclusions: Correction for respiratory motion artifacts using ORG impacts the quantification of metabolic parameters in PDAC lesions. The correlation of metabolic parameters with OS was significantly affected, in particular parameters that describe intra-tumor heterogeneity. Therefore, interpretation of single-voxel or average metabolic parameters in relation to clinical outcome should be done cautiously. Furthermore, ORG is a valuable tool to improve quantification of intra-tumoral heterogeneity in PDAC.
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http://dx.doi.org/10.1186/s13550-019-0492-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6419652PMC
March 2019

Early Recurrence in Completely Resected IIIB and IIIC Melanoma Warrants Restaging Prior to Adjuvant Therapy.

Ann Surg Oncol 2019 Nov 4;26(12):3945-3952. Epub 2019 Mar 4.

Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands.

Purpose: To evaluate the results of restaging completely resected stage IIIB/C melanoma prior to start of adjuvant therapy.

Patients And Methods: One hundred twenty patients with stage IIIB or IIIC (AJCC 2009) melanoma who underwent complete surgical resection were screened for inclusion in our trial investigating adjuvant dendritic cell therapy (NCT02993315). All patients underwent imaging to exclude local relapse or metastasis before entering the trial. The frequency of recurrent disease within 12 weeks after resection and the method of detection were investigated.

Results: Sixty-nine (58%) stage IIIB and 51 (43%) stage IIIC melanoma patients were screened. Median age was 54 (range 27-79) years. Twenty-two (18%) of 120 patients with completely resected stage IIIB/C melanoma had evidence of early recurrent disease, despite exclusion thereof by prior imaging. Median interval between resection and detection of relapse was 7.4 (range 4.3-10.7) weeks. Recurrence was asymptomatic in 17 (77%) patients, but metastasis was noticed by the patient or physician in 5 (23%). Eight patients with local relapse received local treatment with curative intent, and one was treated with systemic therapy. The remaining patients had distant metastasis, 1 of whom underwent resection of a solitary liver metastasis while 12 patients received systemic treatment.

Conclusions: Patients with completely resected stage IIIB/C melanoma have high risk of early recurrence before start of adjuvant therapy. Restaging should be considered for high-risk melanoma patients before start of adjuvant therapy.
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http://dx.doi.org/10.1245/s10434-019-07274-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787294PMC
November 2019

[Ring-shaped lesions on a lung scan].

Ned Tijdschr Geneeskd 2019 01 30;163. Epub 2019 Jan 30.

Radboudumc, afd. Hematologie, Nijmegen.

A 25-year-old man was treated with pembrolizumab for a relapsed-refractory primary mediastinal large B-cell lymphoma. On an evaluation PET-CT scan multiple 'reversed halo signs' were noticed. No infectious cause was established and we diagnosed the lesions as pembrolizumab-induced pneumonitis, an immune-related adverse event.
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January 2019

F-FDG PET/CT-Guided Treatment Duration in Patients with High-Risk Bacteremia: A Proof of Principle.

J Nucl Med 2019 Jul 14;60(7):998-1002. Epub 2018 Dec 14.

Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.

Current guidelines recommend intravenous antibiotic therapy for at least 4 wk in patients with high-risk bacteremia (SAB), because of the risk for metastatic infection. We evaluated the safety of a shorter duration of treatment in patients with high-risk SAB without signs of metastatic infection at presentation, using standard F-FDG PET/CT and echocardiography. Retrospective analyses were performed of patients with SAB admitted between 2013 and 2017 in 2 medical centers. Patients with risk factors for complicated bacteremia (community acquisition, persistently positive blood cultures, >72 h of fever, or foreign body materials present), a normal echocardiography result, and F-FDG PET/CT without signs of metastatic infection were included (cases) and compared with patients with uncomplicated bacteremia (absence of any of the risk factors and no known metastatic disease, controls). Primary outcomes were 3-mo SAB-specific mortality rate and recurrent infection. The secondary outcome was overall mortality. We included 36 cases and 40 controls. Both groups had a similar treatment duration (15.9 vs. 15.4 d). No deaths occurred as a consequence of SAB in the cases, compared with 1 in the control group. One relapse occurred in the case group and 2 in the control group. Overall mortality did not differ between the groups (19.4% vs. 15.0%, = 0.64). This study suggests that intravenous treatment for 2 wk in high-risk patients with SAB without endocarditis and absence of metastatic infection on F-FDG PET/CT is safe. A diagnostic-driven approach using F-FDG PET/CT to determine treatment duration in high-risk SAB seems feasible and allows tailoring treatment to individual patients.
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http://dx.doi.org/10.2967/jnumed.118.221929DOI Listing
July 2019

PD-L1 microSPECT/CT Imaging for Longitudinal Monitoring of PD-L1 Expression in Syngeneic and Humanized Mouse Models for Cancer.

Cancer Immunol Res 2019 01 20;7(1):150-161. Epub 2018 Nov 20.

Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center, Nijmegen, the Netherlands.

Antibodies that block the interaction between programmed death ligand 1 (PD-L1) and PD-1 have shown impressive responses in subgroups of patients with cancer. PD-L1 expression in tumors seems to be a prerequisite for treatment response. However, PD-L1 is heterogeneously expressed within tumor lesions and may change upon disease progression and treatment. Imaging of PD-L1 could aid in patient selection. Previously, we showed the feasibility to image PD-L1 tumors in immunodeficient mice. However, PD-L1 is also expressed on immune cell subsets. Therefore, the aim of this study was to assess the potential of PD-L1 micro single-photon emission tomography/computed tomography (microSPECT/CT) using radiolabeled PD-L1 antibodies to (i) measure PD-L1 expression in two immunocompetent tumor models (syngeneic mice and humanized mice harboring PD-L1 expressing immune cells) and (ii) monitor therapy-induced changes in tumor PD-L1 expression. We showed that radiolabeled PD-L1 antibodies accumulated preferentially in PD-L1 tumors, despite considerable uptake in certain normal lymphoid tissues (spleen and lymph nodes) and nonlymphoid tissues (duodenum and brown fat). PD-L1 microSPECT/CT imaging could also distinguish between high and low PD-L1-expressing tumors. The presence of PD-L1 immune cells did not compromise tumor uptake of the human PD-L1 antibodies in humanized mice, and we demonstrated that radiotherapy-induced upregulation of PD-L1 expression in murine tumors could be monitored with microSPECT/CT imaging. Together, these data demonstrate that PD-L1 microSPECT/CT is a sensitive technique to detect variations in tumor PD-L1 expression, and in the future, this technique may enable patient selection for PD-1/PD-L1-targeted therapy.
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http://dx.doi.org/10.1158/2326-6066.CIR-18-0280DOI Listing
January 2019

Everolimus Exposure and Early Metabolic Response as Predictors of Treatment Outcomes in Breast Cancer Patients Treated with Everolimus and Exemestane.

Target Oncol 2018 10;13(5):641-648

Department of Pharmacy, Radboud Institute for Health Sciences, Radboud university medical center, P.O. Box 9101, 6500 HB, Nijmegen, the Netherlands.

Background: Treating breast cancer patients with everolimus and exemestane can be challenging due to toxicity and suboptimal treatment responses.

Objective: We investigated whether everolimus exposure and early metabolic response are predictors for toxicity and effectiveness in these patients.

Patients And Methods: We performed pharmacokinetic assessments 14 and 35 days after starting treatment. [F]fluorodeoxyglucose-positron emission tomography (F-FDG-PET) was performed at baseline, and 14 and 35 days after the start of the therapy. We recorded toxicity, defined as dose interventions within 3 months, and progression-free survival (PFS).

Results: Among 44 evaluable patients, the geometric mean (GM) C was higher in patients with toxicity compared to patients without (17.4 versus 12.3 μg/L (p = 0.02)). The optimal cut-off value to predict toxicity was C > 19.2 μg/L. GM C of patients with and without progressive disease (PD) within 3 months was not significantly different (12.0 versus 15.2 μg/L (p = 0.118)). In 28 evaluable patients, PD within 3 months could best be predicted using the percentage decrease in peak standardized uptake value normalized by lean body mass of the lesion with highest FDG uptake (SUL) at day 14. Patients with <11% versus >11% decrease in SUL at day 14 had a median PFS of 90 days versus 411 days, respectively (p = 0.0013) and more frequently had PD within 3 months: 70 vs 11%, respectively.

Conclusions: Our results show that everolimus toxicity is related to everolimus C. No relation was observed between everolimus exposure and treatment effectiveness. An early FDG-PET can identify patients at high risk of nonresponse. These results warrant further validation. Clinicaltrials.gov identifier: NCT01948960.
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http://dx.doi.org/10.1007/s11523-018-0596-8DOI Listing
October 2018

The Potential of In Vivo Imaging for Optimization of Molecular and Cellular Anti-cancer Immunotherapies.

Mol Imaging Biol 2018 10;20(5):696-704

Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Geert Grooteplein 10, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.

This review aims to emphasize the potential of in vivo imaging to optimize current and upcoming anti-cancer immunotherapies: spanning from preclinical to clinical applications. Immunotherapies are an emerging class of treatments for a variety of diseases. The agents include molecular and cellular therapeutics, which aim to treat the disease through re-education of the host immune system, often via complex mechanisms of action. In vivo imaging has the potential to contribute in several different ways: (1) as a drug development tool to improve our understanding of their complex mechanisms of action, (2) as a tool to predict efficacy, for example, to stratify patients into probable responders and likely non-responders, and (3) as a non-invasive treatment response biomarker to guide efficient immunotherapy use and to recognize early signs of potential loss of efficacy or resistance in patients. Areas where in vivo imaging is already successfully implemented in onco-immunology research will be discussed and domains where its use offers great potential will be highlighted. The focus of this article is on anti-cancer immunotherapy as it currently is the most advanced immunotherapy area. However, the described concepts can also be paralleled in other immune-mediated disorders and for conditions requiring immunotherapeutic intervention. Importantly, we introduce a new study group within the European Society of Molecular Imaging with the goal to facilitate and enhance immunotherapy development through the use of in vivo imaging.
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http://dx.doi.org/10.1007/s11307-018-1254-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6153672PMC
October 2018

Improving the Diagnostic Performance of F-Fluorodeoxyglucose Positron-Emission Tomography/Computed Tomography in Prosthetic Heart Valve Endocarditis.

Circulation 2018 10;138(14):1412-1427

Department of Radiology and Nuclear Medicine (L.E.S., G.P.K., R.P.J.B.), Erasmus Medical Center, Rotterdam, The Netherlands.

Background: F-Fluorodeoxyglucose (FDG) positron-emission tomography/computed tomography (PET/CT) was recently introduced as a new tool for the diagnosis of prosthetic heart valve endocarditis (PVE). Previous studies reporting a modest diagnostic accuracy may have been hampered by unstandardized image acquisition and assessment, and several confounders, as well. The aim of this study was to improve the diagnostic performance of FDG PET/CT in patients in whom PVE was suspected by identifying and excluding possible confounders, using both visual and standardized quantitative assessments.

Methods: In this multicenter study, 160 patients with a prosthetic heart valve (median age, 62 years [43-73]; 68% male; 82 mechanical valves; 62 biological; 9 transcatheter aortic valve replacements; 7 other) who underwent FDG PET/CT for suspicion of PVE, and 77 patients with a PV (median age, 73 years [65-77]; 71% male; 26 mechanical valves; 45 biological; 6 transcatheter aortic valve replacements) who underwent FDG PET/CT for other indications (negative control group), were retrospectively included. Their scans were reassessed by 2 independent observers blinded to all clinical data, both visually and quantitatively on available European Association of Nuclear Medicine Research Ltd-standardized reconstructions. Confounders were identified by use of a logistic regression model and subsequently excluded.

Results: Visual assessment of FDG PET/CT had a sensitivity/specificity/positive predictive value/negative predictive value for PVE of 74%/91%/89%/78%, respectively. Low inflammatory activity (C-reactive protein <40 mg/L) at the time of imaging and use of surgical adhesives during prosthetic heart valve implantation were significant confounders, whereas recent valve implantation was not. After the exclusion of patients with significant confounders, diagnostic performance values of the visual assessment increased to 91%/95%/95%/91%. As a semiquantitative measure of FDG uptake, a European Association of Nuclear Medicine Research Ltd-standardized uptake value ratio of ≥2.0 was a 100% sensitive and 91% specific predictor of PVE.

Conclusions: Both visual and quantitative assessments of FDG PET/CT have a high diagnostic accuracy in patients in whom PVE is suspected. FDG PET/CT should be implemented early in the diagnostic workup to prevent the negative confounding effects of low inflammatory activity (eg, attributable to prolonged antibiotic therapy). Recent valve implantation was not a significant predictor of false-positive interpretations, but surgical adhesives used during implantation were.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.118.035032DOI Listing
October 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

F-FDG PET/CT in Local Ablative Therapies: A Systematic Review.

J Nucl Med 2018 04 18;59(4):551-556. Epub 2018 Jan 18.

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

Driven by the continuous improvement in the accuracy of cross-sectional imaging, image-guided minimally invasive local ablative therapies have received incremental interest over the past few years. In this article, we systematically review the currently available literature on F-FDG PET/CT to monitor the efficacy of these local ablative therapies. By including all local ablative treatment modalities, tumor types, and organ sites, we provide a comprehensive overview of the current status, identify general patterns across studies, and provide recommendations for future studies and clinical practice. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) criteria were used to assess the quality of the reported diagnostic accuracy of the retrieved studies. Data in the literature suggest that F-FDG PET/CT is a highly accurate tool to assess the technical success of local treatment, to identify residual or recurrent tumor early after intervention, and to provide prognostic and predictive information. However, prospective interventional studies based on F-FDG PET/CT findings of disease activity are mandatory to develop uniform and quantitative criteria for PET evaluation. Moreover, the optimal timing of F-FDG PET/CT after treatment may vary according to the location of the disease, with very early imaging being possible in solid organs such as the liver but posttreatment imaging being challenging for 3 mo in a location such as the lung parenchyma.
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http://dx.doi.org/10.2967/jnumed.117.198184DOI Listing
April 2018

In-vivo imaging of tumor-infiltrating immune cells: implications for cancer immunotherapy.

Q J Nucl Med Mol Imaging 2018 Mar 30;62(1):56-77. Epub 2017 Nov 30.

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

Dynamic interactions between tumor cells and immune cells promote the initiation, progression, metastasis and therapy-resistance of cancer. With respect to immunotherapy, immune cell populations such as cytotoxic CD8+ T-cells, CD56+ NK cells and myeloid phagocytic cells play decisive roles. From an imaging perspective, the immune system displays unique challenges, which have implications for the design and performance of studies. The immune system comprises highly mobile cells that undergo distinct phases of development and activation. These cells circulate through several compartments during their active life span and accumulate in rather limited numbers in cancer lesion, where their effector phenotype further diversifies. Given these features, accurate evaluation of the tumor microenvironment and its cellular components during anti-cancer immunotherapy is challenging. In-vivo imaging currently offers quantitative and sensitive modalities that exploit long-lived tracers to interrogate, e.g. distinct immune cell populations, metabolic phenotypes, specific targets relevant for therapy or critical for their effector function. This review provides a comprehensive overview of current status for in-vivo imaging tumor-infiltrating immune cell populations, focusing on lymphocytes, NK cells and myeloid phagocytic cells, with emphasis on clinical translation.
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http://dx.doi.org/10.23736/S1824-4785.17.03052-7DOI Listing
March 2018

F-FDG PET/CT Optimizes Treatment in Bacteremia and Is Associated with Reduced Mortality.

J Nucl Med 2017 09 23;58(9):1504-1510. Epub 2017 Mar 23.

Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.

Metastatic infection is an important complication of bacteremia (SAB). Early diagnosis of metastatic infection is crucial, because specific treatment is required. However, metastatic infection can be asymptomatic and difficult to detect. In this study, we investigated the role of F-FDG PET/CT in patients with SAB for detection of metastatic infection and its consequences for treatment and outcome. All patients with SAB at Radboud University Medical Center were included between January 2013 and April 2016. Clinical data and results of F-FDG PET/CT and other imaging techniques, including echocardiography, were collected. Primary outcomes were newly diagnosed metastatic infection by F-FDG PET/CT, subsequent treatment modifications, and patient outcome. A total of 184 patients were included, and F-FDG PET/CT was performed in 105 patients, of whom 99 had a high-risk bacteremia. F-FDG PET/CT detected metastatic infectious foci in 73.7% of these high-risk patients. In 71.2% of patients with metastatic infection, no signs and symptoms suggesting metastatic complications were present before F-FDG PET/CT was performed. F-FDG PET/CT led to a total of 104 treatment modifications in 74 patients. Three-month mortality was higher in high-risk bacteremia patients without F-FDG PET/CT performed than in those in whom F-FDG PET/CT was performed (32.7% vs. 12.4%, = 0.003). In multivariate analysis, F-FDG PET/CT was the only factor independently associated with reduced mortality ( = 0.005; odds ratio, 0.204; 95% confidence interval, 0.066-0.624). A higher comorbidity score was independently associated with increased mortality ( = 0.003; odds ratio, 1.254; 95% confidence interval, 1.078-1.457). F-FDG PET/CT is a valuable technique for early detection of metastatic infectious foci, often leading to treatment modification. Performing F-FDG PET/CT is associated with significantly reduced 3-mo mortality.
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http://dx.doi.org/10.2967/jnumed.117.191981DOI Listing
September 2017

Adjuvant dendritic cell vaccination induces tumor-specific immune responses in the majority of stage III melanoma patients.

Oncoimmunology 2016 Jul 31;5(7):e1191732. Epub 2016 May 31.

Department of Medical Oncology, Radboud University Medical Center Nijmegen, Nijmegen, the Netherlands; Department of Tumor Immunology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands.

Purpose: To determine the effectiveness of adjuvant dendritic cell (DC) vaccination to induce tumor-specific immunological responses in stage III melanoma patients.

Experimental Design: Retrospective analysis of stage III melanoma patients, vaccinated with autologous monocyte-derived DC loaded with tumor-associated antigens (TAA) gp100 and tyrosinase after radical lymph node dissection. Skin-test infiltrating lymphocytes (SKILs) obtained from delayed-type hypersensitivity skin-test biopsies were analyzed for the presence of TAA-specific CD8(+) T cells by tetrameric MHC-peptide complexes and by functional TAA-specific T cell assays, defined by peptide-recognition (T2 cells) and/or tumor-recognition (BLM and/or MEL624) with specific production of Th1 cytokines and no Th2 cytokines.

Results: Ninety-seven patients were analyzed: 21 with stage IIIA, 34 with stage IIIB, and 42 had stage IIIC disease. Tetramer-positive CD8(+) T cells were present in 68 patients (70%), and 24 of them showed a response against all 3 epitopes tested (gp100:154-162, gp100:280-288, and tyrosinase:369-377) at any point during vaccinations. A functional T cell response was found in 62 patients (64%). Rates of peptide-recognition of gp100:154-162, gp100:280-288, and tyrosinase:369-377 were 40%, 29%, and 45%, respectively. Median recurrence-free survival and distant metastasis-free survival of the whole study population were 23.0 mo and 36.8 mo, respectively.

Conclusions: DC vaccination induces a functional TAA-specific T cell response in the majority of stage III melanoma patients, indicating it is more effective in stage III than in stage IV melanoma patients. Furthermore, performing multiple cycles of vaccinations enhances the chance of a broader immune response.
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http://dx.doi.org/10.1080/2162402X.2016.1191732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5006921PMC
July 2016

A comparison of the diagnostic value of MRI and F-FDG-PET/CT in suspected spondylodiscitis.

Infection 2017 Feb 17;45(1):41-49. Epub 2016 Jun 17.

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

Purpose: The purpose of this study was to evaluate the diagnostic value of F-fluorodeoxyglucose (FDG) positron emission tomography and computed tomography (PET/CT scan) and magnetic resonance imaging (MRI) in diagnosing spondylodiscitis and its complications, such as epidural and paraspinal abscesses.

Methods: From January 2006 to August 2013 patients with a clinical suspicion of spondylodiscitis, with an infection, or with fever of unknown origin were retrospectively included if F-FDG-PET/CT and MRI of the spine were performed within a 2-week time span. Imaging results were compared to the final clinical diagnosis and follow-up data were collected.

Results: Sixty-eight patients were included of whom 49 patients were diagnosed with spondylodiscitis. MRI showed an overall sensitivity of 67 % and specificity of 84 %. Diagnostic accuracy was 58 %, when MRI was performed within 2 weeks after the start of symptoms and improved to 82 %, when performed more than 2 weeks after onset of symptoms. F-FDG-PET/CT showed a sensitivity of 96 % and a specificity of 95 %, with no relation to the interval between the scan and the start of symptoms.

Conclusions: As compared to MRI, F-FDG-PET/CT has superior diagnostic value for detecting early spondylodiscitis. After 2 weeks both techniques perform similarly.
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http://dx.doi.org/10.1007/s15010-016-0914-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5306365PMC
February 2017
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