NUCLEAIRE GENEESKUNDE

CENTRUM NUCLEAIRE GENEESKUNDE

ARTIKELS

ABSTRACT 1

PSMA-targeting positron emission agents for imaging solid tumors other than non-prostate carcinoma: a systematic review.

Van de Wiele C, Maes A, De Jonghe P, Beels L, et al. International Journal of Molecular Sciences, 2019, 20(19), pii: E4886

INTRODUCTION/BACKGROUND Despite its name, prostate-specific membrane antigen (PSMA) has been shown using immunohistochemistry (IHC) to also be over-expressed in the tumor neovasculature of a wide variety of solid tumors other than prostate carcinoma. Accordingly, positron-emitting radiolabeled small molecules targeting PSMA, initially developed for positron emission tomography in prostate carcinomas, are currently being explored for their staging and restaging potential as an alternative imaging modality in other solid tumor types where 18-F-fluorodeoxyglucose (FDG)-PET imaging has low diagnostic accuracy.

OBJECTIVE In this paper, the currently available literature in this field is reviewed.

RESULTS Preliminary, mainly retrospective studies are encouraging, with evidence of improved diagnostic sensitivity and specificity in clear cell renal carcinoma, glioma, and hepatocellular carcinoma, leading to a change in patient management in several patients. However, the results published thus far warrant confirmation by larger prospective studies additionally assessing the longitudinal impact on patient outcomes.

ABSTRACT 2

Predictors of overall and disease-free survival in metastatic castration-resistant prostate cancer patients receiving 225ac-psma-617 radioligand therapy.

Sathekge M, Van de Wiele C, Maes A, et al. Journal of Nuclear Medicine, 2020, 61(1), 62-69

INTRODUCTION/BACKGROUND Metastatic prostate carcinoma overexpresses prostate-specific membrane antigen (PSMA), making this antigen a suitable target for radioligand therapy of the disease. Here we report on our experience with a series of 73 castration-resistant prostate carcinoma patients treated with 225Ac-PSMA-617, identifying variables predictive for overall survival (OS) and progression-free survival (PFS) after 225Ac-PSMA-617 treatment.

MATERIALS/METHODS 225Ac-PSMA-617 was administered to patients who had metastatic castration-resistant prostate carcinoma and who had exhausted available therapy options for their disease. Full blood count, glomerular filtration rate, and liver function test were obtained at baseline and on follow-up for evaluation of toxicity. 68Ga-PSMA PET/CT was obtained at baseline, before every treatment cycle, and on follow-up for selection of patients for treatment, to determine the activity of the treatment agent to be administered, and for response assessment. Serial prostate-specific antigen (PSA) was obtained for PSA response assessment.

RESULTS Seventy-three men (mean age, 69 y; range, 45-85 y) with metastatic castration-resistant prostate carcinoma were treated with 210 cycles of 225Ac-PSMA-617. In 70% of patients, a PSA decline of greater than or equal to 50% was obtained; 82% of patients had any PSA decline. In 29% of patients, all lesions on 68Ga-PSMA PET resolved in response to treatment. During follow-up, 23 patients experienced disease progression, whereas 13 patients died from their disease. The estimated median PFS and OS were 15.2 mo (95% CI, 13.1-17.4) and 18 mo (95% CI, 16.2-19.9), respectively. In univariate analyses, factors such as baseline PSA, any PSA decline, PSA decline of greater than or equal to 50%, prior chemotherapy, prior radiation therapy, and baseline hemoglobin level were associated with longer PFS and OS (all Ps < 0.05). In multivariate analyses, there was a negative association between prior 177Lu-PSMA therapy and PFS, and a positive association between PSA decline of greater or equal to 50% and PFS. Only a PSA decline of greater than or equal to 50% remained significantly associated with OS on multivariate analyses. Xerostomia was seen in 85% of patients but was not severe enough to warrant discontinuing treatment. Anemia was seen in 27 patients; no patients had grade IV bone marrow toxicity. Renal failure of grade III or IV was seen in 5 patients with baseline renal impairment.

CONCLUSION In this study, a PSA decline of greater than or equal to 50% after treatment with 225Ac-PSMA-617 was proven by multivariate analyses to be significantly associated with OS and

PFS. Furthermore, previous 177Lu-PSMA treatment was negatively associated with PFS in both univariate and multivariate analyses.

ABSTRACT 3

18F-FDG-PET/CT imaging of uterine cervical cancer recurrence in women with and without HIV infection.

Lawal I, Maes A, Van de Wiele C, et al. The Quarterly Journal of Nuclear Medicine and Molecular Imaging, 2019, Epub ahead of print, DOI: 10.23736/S18244785

INTRODUCTION/BACKGROUND To compare the rate, time and, pattern of recurrence of cervical cancer between patients with and without HIV infection and to determine factors predicting cervical cancer recurrence in patients evaluated by 18F-FDG-PET/CT.

MATERIALS/METHODS We reviewed the 18F-FDG-PET/CT images of patients with histologically proven cervical carcinoma who were presenting with suspected recurrence. We extracted epidemiologic data, previous treatment, histologic subtype, HIV status, viral load and CD4 counts from the electronic laboratory database and the referral form for the 18F-FDG-PET/CT study.

RESULTS We studied 303 women including 112 HIV-infected patients. FIGO stage III disease was present in 131 patients. Of 198 patients with recurrence, 74 were HIV-infected while 124 were not (p=0.849). HIV infected patients were younger (41.99 ± 9.30 years) compared to HIV-uninfected (50.19 ± 11.09), p<0.001. Local recurrence was present in 125 patients while 100 patients had a distant recurrence. Recurrence occurred at a single site in 88 patients and two or more sites in 110 patients. No significant difference in the recurrent patterns between HIV-infected and uninfected patients. Median time to recurrence was 10.50 months (Range: 6.00-156.00) among HIV-infected versus 12.00 months (IQR:7.00-312.00) among the uninfected, p=0.065. FIGO stage III (p=0.042) and the presence of histological sub-types other than SCC (p=0.005) were significant predictors of recurrence. HIV infection by itself was not significant in predicting recurrence (p=0.843).

CONCLUSION HIV infection has no significant impact on the rate, time or pattern of recurrence in women with suspected cervical carcinoma recurrence. Advanced disease and histological variant other than SCC are predictive of recurrence.

ABSTRACT 4

Low septal to lateral wall 18F-FDG ratio is highly associated with mechanical dyssynchrony in nonischemic CRT candidates.

Degtiarova G, Claus P, Gheysens O, et al. European Journal of Nuclear Medicine and Molecular Imaging Research, 2019, 9(1), 105

INTRODUCTION/BACKGROUND In order to better understand the concept of mechanical dyssynchrony, a promising hallmark of cardiac resynchronization therapy (CRT) response, we investigated its effect on regional myocardial metabolism and myocardial blood flow (MBF) in non-ischemic CRT candidates.

RESULTS Thirty consecutive non-ischemic CRT eligible patients underwent static 18F-FDG and resting dynamic 13N-NH3 PET/ CT. 18F-FDG uptake and MBF for septal and lateral wall were analysed and septal-to-lateral wall ratios (SLR) were calculated. Based on the presence of mechanical dyssynchrony (septal flash and/or apical rocking) on echocardiography, patients were divided into 2 groups, with (n = 23) and without (n = 7) mechanical dyssynchrony. Patients with mechanical dyssynchrony had significantly lower 18F-FDG SUVmean in the septum compared with the lateral wall (5.58 ± 2.65 vs 11.19 ± 4.10, p < 0.0001), while patients without mechanical dyssynchrony had a more homogeneous 18F-FDG distribution (7.33 ± 2.88 vs 8.31 ± 2.50, respectively, p = 0.30). Similarly, MBF was significantly different between the septal and lateral wall in the dyssynchrony group (0.57 ± 0.11 ml/g/min vs 0.92 ± 0.23 ml/g/min, respectively, p < 0.0001), whereas no difference was observed in the non-dyssynchrony group (0.61 ± 0.23 ml/g/min vs 0.77 ± 0.21 ml/g/min, respectively, p = 0.16). 18F-FDG SLR, but not MBF SLR, was associated with the presence of mechanical dyssynchrony and showed a significant inverse correlation with volumetric reverse remodeling after CRT (r = - 0.62, p = 0.001).

CONCLUSION Non-ischemic heart failure patients with mechanical dyssynchrony demonstrate heterogeneous regional metabolism and MBF compared with patients without dyssynchrony. However, only 18F-FDG SLR appeared to be highly associated with the presence of mechanical dyssynchrony.

ABSTRACT 5

Granulomatosis with polyangiitis with breast involvement mimicking metastatic cancer: Case report and literature review.

Gadeyne L, Henckaerts L, Gheysens O, et al. European Journal of Rheumatology, 2019, 7(1), 41-43

INTRODUCTION/BACKGROUND Granulomatosis with polyangiitis (GPA) is a systemic inflammatory disease, characterized by the presence of necrotizing vasculitis of small and medium-sized vessels, granulomatous inflammation and anti-neutrophil cytoplasmic antibodies (ANCAs). The diagnosis can be challenging due to the variable clinical presentation and possible involvement of virtually all organ systems. A correct diagnosis is indispensable for a timely start of medical treatment and to avoid unnecessary surgery. Therefore, cooperation with and the input of the pathologist is crucial. We report a case of a woman presenting with suspected metastatic cancer. The diagnosis of GPA was made mainly based on breast biopsy, and the patient was treated accordingly, with full recovery. This report provides a case description and a brief review of the literature.

ABSTRACT 6

Anatomical mapping of lymph nodes in patients receiving salvage lymphadenectomy based on a positive 11C-choline positron emission tomography/computed tomography scan.

Deconinck S, Tosco L, Gheysens O, et al. Central European Journal of Urology, 2019, 72(3), 232-239

INTRODUCTION/BACKGROUND This paper aims to assess the diagnostic accuracy of an 11C-choline positron emission tomography/computed tomography (PET/CT) scan in the detection of lymph node (LN) metastases in patients with biochemical recurrence after radically treated prostate cancer (PCa), as compared to histology. The secondary goal is to depict spreading patterns of metastatic LNs in recurrent PCa.

MATERIALS/METHODS A single center retrospective study comprising of 30 patients who underwent retroperitoneal and/or pelvic salvage lymph node dissection (LND) due to 11C-choline PET/CT-positive nodal recurrences after radical treatment (median Prostate Specific Antigen (PSA) 1.5 ng/ml, range 0.2-11.4). Positive nodes on the preoperative PET/CT scans were mapped and compared to post-operative pathology results. LNs were marked as true positive, false positive, true negative and false negative and a patient- and a region-based analysis was performed. Sensitivity, specificity and positive/negative predictive value (PPV/NPV) were calculated.

RESULTS Sixty positive LNs were detected on PET/CT with a median number of two positive nodes per patient (range 1-6). In 29 patients, a super-extended pelvic LND (PLND) was performed combined with a retroperitoneal LND (RPLND) in 13 of those cases. One patient underwent an inguinal LND. One hundred thirty-seven of 644 resected LNs contained metastases. The 11C-choline PET/CT scan correctly predicted 31 positive nodes (55%) while 25 nodes were falsely positive (45%). One hundred and six histologically proven metastatic nodes were not detected on the 11C-choline PET/CT scan (77%). Sensitivity, specificity, PPV and NPV of the 11C-choline PET/CT were 23%, 95%, 55% and 82%, respectively.

CONCLUSION 11C-choline PET/CT has a relatively low detection rate and a moderate PPV for metastatic LNs in patients with biochemical recurrence after radically treated PCa.

ABSTRACT 7

Natural evolution of cardiac sarcoidosis in an asymptomatic patient: a case report.

Degtiarova G, Gheysens O, Van Cleemput J, et al. European Heart Journal - Case Reports, 2019, 3(3), ytz099

INTRODUCTION/BACKGROUND Sarcoidosis is a multi-organ granulomatous disease of unknown aetiology. Adverse outcome related with cardiac involvement, makes early diagnosis of cardiac sarcoidosis crucial.

RESULTS In a 55-year-old man presenting with recurrent pulmonary infections, computed tomography (CT) showed several enlarged mediastinal lymph nodes and no lung pathology. Subsequent mediastinoscopy revealed the diagnosis of sarcoidosis. Further screening for organ involvement showed multifocal cardiac involvement both on cardiac magnetic resonance (CMR) and 18-F-fluorodeoxyglucose-positron emission tomography-computed tomography (18F-FDG

PET-CT). Because of the lack of functional deterioration and clinical symptoms, no steroid treatment was initiated and regular follow-up of cardiac abnormalities was performed by CMR. Unremarkable progression of cardiac involvement during the first 2 years of follow-up turned into a dramatic involvement after 4 years, with the increase in the number and size of lesions at late gadolinium enhancement (LGE) CMR. Late gadolinium enhancement areas matched the regions of strongly increased 18F-FDG uptake. For the first time, the patient started complaining on shortness of breath, electrocardiography showed an atrioventricular block Grade 1. Cardiac biomarkers and cardiac function were still preserved. Steroid treatment was started. Although an electrophysiology study was negative, Holter monitoring showed ventricular arrhythmia. Cardioverter-defibrillator was implanted.

CONCLUSION This case shows the progression of cardiac sarcoidosis on CMR in an asymptomatic untreated patient over a 4-year period, and rises the awareness of possible severe cardiac damage even in the absence of clinical signs of cardiac involvement. Combination of PET and CMR is appealing to better understand the evolution of cardiac sarcoidosis and may help in the management of such patients.

ABSTRACT 8

Regional myocardial work by cardiac magnetic resonance and non-invasive left ventricular pressure: a feasibility study in left bundle branch block.

Larsen C, Aalen J, Gheysens O, et al. European Heart Journal - Cardiovascular Imaging, 2020, 21(2), 143-153

OBJECTIVE Regional myocardial work may be assessed by pressure-strain analysis using a non-invasive estimate of left ventricular pressure (LVP). Strain by speckle tracking echocardiography (STE) is not always accessible due to poor image quality. This study investigated the estimation of regional myocardial work from strain by feature tracking (FT) cardiac magnetic resonance (CMR) and non-invasive LVP.

MATERIALS/METHODS Thirty-seven heart failure patients with reduced ejection fraction, left bundle branch block (LBBB), and no myocardial scar were compared to nine controls without LBBB. Circumferential strain was measured by FT-CMR in a mid-ventricular short-axis cine view, and longitudinal strain by STE. Segmental work was calculated by pressure-strain analysis. Twenty-five patients underwent 18F-fluorodeoxyglucose (FDG) positron emission tomography. Segmental values were reported as percentages of the segment with maximum myocardial FDG uptake. In LBBB patients, net CMR-derived work was 51 ± 537 (mean ± standard deviation) in septum vs. 1978 ± 1084 mmHg·% in the left ventricular (LV) lateral wall (P < 0.001). In controls, however, there was homogeneous work distribution with similar values in septum and the LV lateral wall (non-significant). Reproducibility was good. Segmental CMR-derived work correlated with segmental STE-derived work and with segmental FDG uptake (average r = 0.71 and 0.80, respectively).

CONCLUSION FT-CMR in combination with non-invasive LVP demonstrated markedly reduced work in septum compared to the LV lateral wall in patients with LBBB. Work distribution correlated with STE-derived work and energy demand as reflected in FDG uptake. These results suggest that FT-CMR in combination with non-invasive LVP is a relevant clinical tool to measure regional myocardial work.

ABSTRACT 9

Impact of left bundle branch block on myocardial perfusion and metabolism: A positron emission tomography study.

Degtiarova G, Claus P, Gheysens O, et al. Journal of Nuclear Cardiology, 2019, Oct 2, doi: 10.1007/ s12350-019-01900-y

INTRODUCTION/BACKGROUND Better understanding of pathophysiological changes, induced by left bundle branch block (LBBB), may improve patient selection for cardiac resynchronization therapy (CRT). Therefore, we assessed the effect of LBBB on regional glucose metabolism, 13N-NH3-derived absolute and semiquantitative myocardial blood flow (MBF), and their relation in non-ischemic CRT candidates.

MATERIALS/METHODS Twenty-five consecutive non-ischemic patients with LBBB underwent 18F-FDG and resting dynamic 13N-NH3 PET/ CT prior to CRT implantation. Regional 18F-FDG uptake, absolute MBF, and late 13N-NH3 uptake were analyzed and corresponding septal-to-lateral wall ratios (SLR) were calculated. Segmental analysis was performed to evaluate "reverse mismatch," "mismatch," and "match" patterns, based on late 13N-NH3/18F-FDG uptake ratios.

RESULTS A significantly lower 18F-FDG uptake was observed in the septum compared to the lateral wall (SLR 0.53 ± 0.17). A similar pattern was observed for MBF (SLR 0.68 ± 0.18), whereas late 13N-NH3 uptake showed a homogeneous distribution (SLR 0.96 ± 0.13). 13N-NH3/18F-FDG "mismatch" and "reverse mismatch" segments were predominantly present in the lateral (52%) and septal wall (61%), respectively.

CONCLUSION Non-ischemic CRT candidates with LBBB demonstrate lower glucose uptake and absolute MBF in the septum compared to the lateral wall. However, late static 13N-NH3 uptake showed a homogenous distribution, reflecting a composite measure of altered regional MBF and metabolism, induced by LBBB.

ABSTRACT 10

PET or MRI to improve response evaluation in clinical trials?

Deroose C, Gheysens O, Perez-Lopez R, et al. The Lancet Oncology, 2019, 20(8), 1060-1062

Er is geen abstract beschikbaar.

ABSTRACT 11

Cholesterol lowering attenuates pressure overload-induced heart failure in mice with mild hypercholesterolemia.

Muthurama I, Mishra M, Gheysens O, et al. Aging (Albany New York), 2019, 11(17), 6872-6891

INTRODUCTION/BACKGROUND Epidemiological studies support a strong association between non-high-density lipoprotein cholesterol levels and heart failure incidence. The objective of the current study was to evaluate the effect of selective cholesterol lowering adeno-associated viral serotype 8 (AAV8)-mediated low-density lipoprotein receptor (LDLr) gene transfer on cardiac remodelling and myocardial oxidative stress following transverse aortic constriction (TAC) in female C57BL/6 LDLr-/- mice with mild hypercholesterolemia. Cholesterol lowering gene transfer resulted in a 65.9% (p<0.0001) reduction of plasma cholesterol levels (51.2 ± 2.2 mg/dl) compared to controls (150 ± 7 mg/dl). Left ventricular wall area was 11.2% (p<0.05) lower in AAV8-LDLr TAC mice than in control TAC mice. In agreement, pro-hypertrophic myocardial proteins were potently decreased in AAV8-LDLr TAC mice. The degree of interstitial fibrosis and perivascular fibrosis was 31.0% (p<0.001) and 29.8% (p<0.001) lower, respectively, in AAV8-LDLr TAC mice compared to control TAC mice. These structural differences were associated with improved systolic and diastolic function and decreased lung congestion in AAV8-LDLr TAC mice compared to control TAC mice. Cholesterol lowering gene therapy counteracted myocardial oxidative stress and preserved the potential for myocardial fatty acid oxidation in TAC mice. In conclusion, cholesterol lowering gene therapy attenuates pressure overload-induced heart failure in mice with mild hypercholesterolemia.

ABSTRACT 12

ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI expert consensus recommendations for multimodality imaging in cardiac amyloidosis: Part 1 of 2-evidence base and standardized methods of imaging.

Dorbala S, Ando Y, Gheysens O, et al. Journal of Cardiac Failure, 2019, 25(11), e1-e39

Er is geen abstract beschikbaar.

ABSTRACT 13

ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI expert consensus recommendations for multimodality imaging in cardiac amyloidosis: Part 2 of 2-diagnostic criteria and appropriate utilization.

Dorbala S, Ando Y, Gheysens O, et al. Journal of Cardiac Failure, 2019, 25(11), 854-865

INTRODUCTION/BACKGROUND Cardiac amyloidosis is emerging as an underdiagnosed cause of heart failure and mortality. Growing literature suggests that a noninvasive diagnosis of cardiac amyloidosis is now feasible. However, the diagnostic criteria and utilization of imaging in cardiac amyloidosis are not standardized. In this paper, Part 2 of a series, a panel of international experts from multiple societies define the diagnostic criteria for cardiac amyloidosis and appropriate utilization of echocardiography, cardiovascular magnetic resonance imaging, and radionuclide imaging in the evaluation of patients with known or suspected cardiac amyloidosis.

ABSTRACT 14

Role of 18F-FDG PET/CT in restrictive allograft syndrome after lung transplantation.

Verleden S, Gheysens O, Goffin K, et al. Transplantation, 2019, 103(4), 823-831

INTRODUCTION/BACKGROUND Differential diagnosis of phenotypes of chronic lung allograft dysfunction (CLAD) remains troublesome. We hypothesized that F-FDG PET/CT may help in differential diagnosis of CLAD phenotypes, as it showed promising results regarding diagnosis and prognosis in interstitial lung diseases.

MATERIALS/METHODS A monocentric, retrospective study was performed including all lung transplant recipients suffering from bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS) who underwent F-FDG PET/CT scan, in comparison with stable lung transplant recipients. Maximum standardized uptake value (SUVmax) was associated with pulmonary function and survival. Proof-of-concept microCT and glucose transporter-1 (GLUT1) staining served as morphologic validation for regions with different SUVmax.

RESULTS Maximum standardized uptake value was higher in RAS (median, 2.6; n = 29) compared with BOS (median, 1.0; n = 15) and stable patients (median, 0.59; n = 8) (P < 0.0001). In RAS, high SUVmax was associated with worse survival after F-FDG PET/CT (P = 0.0004; hazard ratio, 1.82). Forced vital capacity at F-FDG PET/CT inversely correlated with SUVmax (R = -0.40, P = 0.03). MicroCT analysis revealed extensive fibrosis in regions of high SUVmax, with an increased number of glucose transporter-1-positive cells.

CONCLUSION F-fluorodeoxyglucose positron emission tomography with CT may noninvasively differentiate RAS from BOS. RAS patients with areas of increased lung metabolism have worse outcome, demonstrating the potential use of F-FDG PET/ CT during follow-up after lung transplantation. ABSTRACT 15

Papillary muscles contribute significantly more to left ventricular work in dilated hearts.

Duchenne J, Turco A, Gheysens O, et al. European Heart Journal - Cardiovascular Imaging, 2019, 20(1), 84-91

OBJECTIVE Left ventricular (LV) dilatation results in increased sphericity and affects position and orientation of papillary muscles (PMs), which may influence their performed work. The aim of this study was to assess the contribution of PM to LV function and its changes with dilatation.

MATERIALS/METHODS Fifteen sheep were investigated. Ten animals were subjected to 8 weeks of rapid (180 bpm) pacing, inducing LV dilatation. Five animals served as controls. High-resolution gated computed tomography was performed to assess LV volumes, left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), sphericity index, and PM angle, width and fractional shortening. 18F-fluorodeoxyglucose positron emission tomography (PET) was used to measure glucose metabolism as surrogate of regional myocardial work. Spatial resolution of PET images was maximized by electrocardiogram- and respiratory-gating. 18F-fluorodeoxyglucose uptake was measured in PM and compared with remaining left ventricular myocardium (MYO) to obtain a PM/MYO ratio.

RESULTS Animals with dilated heart had a more spherical left ventricle, with reduced LVEF (P < 0.0001) and GLS (P < 0.0001). In dilated hearts, PET analysis revealed a higher contribution of both PM to LV myocardial work (P < 0.0001); and PM angle towards LV wall correlated with PM work, together with PM width and the LV sphericity index. Sphericity index and posterior PM angle were strongest determinants of posterior PM/MYO ratio (R2 = 0.754; P < 0.0001), while anterior PM/MYO was mostly determined by sphericity index and the PM width (R2 = 0.805; P < 0.0001).

CONCLUSION In dilated hearts, PM contribute relatively more to LV myocardial work. We hypothesize that this is caused by the more cross-sectional orientation of the subvalvular apparatus, which leads to a higher stress on the PM compared with the spherical LV walls. The reduced cross-sectional area of the PM may further explain their increased stress.

ABSTRACT 16

Diagnosis of peripheral bone and prosthetic joint infections: overview on the consensus documents by the EANM, EBJIS, and ESR (with ESCMID endorsement).

Scofienza LM, Signore A, Gheysens O, et al. European Radiology, 2019, 29(12), 6425-6438

OBJECTIVE Peripheral bone infection (PBI) and prosthetic joint infection (PJI) are two different infectious conditions of the musculoskeletal system. They have in common to be quite challenging to be diagnosed and no clear diagnostic flowchart has been established. Thus, a conjoined initiative on these two topics has been initiated by the European Society of Radiology (ESR), the European Association of Nuclear Medicine (EANM), the European Bone and Joint Infection Society (EBJIS), and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). The purpose of this work is to provide an overview on the two consensus documents on PBI and PJI that originated by the conjoined work of the ESR, EANM, and EBJIS (with ESCMID endorsement).

MATERIALS/METHODS After literature search, a list of 18 statements for PBI and 25 statements for PJI were drafted in consensus on the most debated diagnostic challenges on these two topics, with emphasis on imaging.

CONCLUSION Overall, white blood cell scintigraphy and magnetic resonance imaging have individually demonstrated the highest diagnostic performance over other imaging modalities for the diagnosis of PBI and PJI. However, the choice of which advanced diagnostic modality to use first depends on several factors, such as the benefit for the patient, local experience of imaging specialists, costs, and availability. Since robust, comparative studies among most tests do not exist, the proposed flowcharts are based not only on existing literature but also on the opinion of multiple experts involved on these topics. Key points:

1. For peripheral bone infection and prosthetic joint infection, white blood cell and magnetic resonance imaging have individually demonstrated the highest diagnostic performance over other imaging modalities. 2. Two evidence- and expert-based diagnostic flowcharts involving variable combination of laboratory tests, biopsy methods, and radiological and nuclear medicine imaging modalities are proposed by a multi-society expert panel. 3. Clinical application of these flowcharts depends on several factors, such as the benefit for the patient, local experience, costs, and availability.

ABSTRACT 17

Letter to the Editor regarding Falstie-Jensen et al: "Labeled white blood cell/bone marrow single-photon emission computed tomography with computed tomography fails in diagnosing chronic periprosthetic shoulder joint infection".

Wouthuyzen-Bakker M, Gheysens O, et al. Journal of Shoulder and Elbow Surgery, 2019, 28(7), e250-e251

Er is geen abstract beschikbaar.

ABSTRACT 18

Dose-dependent improvement of cardiac function in a swine model of acute myocardial infarction after intracoronary administration of allogeneic heartderived cells.

Crisomoto V, Baez C, Gheysens O, et al. Stem Cell Research & Therapy, 2019, 10(1), 152

INTRODUCTION/BACKGROUND Allogeneic cardiac-derived progenitor cells (CPC) without immunosuppression could provide an effective ancillary therapy to improve cardiac function in reperfused myocardial infarction. We set out to perform a comprehensive preclinical feasibility and safety evaluation of porcine CPC (pCPC) in the infarcted porcine model, analyzing biodistribution and mid-term efficacy, as well as safety in healthy non-infarcted swine.

MATERIALS/METHODS The expression profile of several pCPC isolates was compared with humans using both FACS and RT-qPCR. ELISA was used to compare the functional secretome. One week after infarction, female swine received an intracoronary (IC) infusion of vehicle (CON), 25 × 106 pCPC (25 M), or 50 × 106 pCPC (50 M). Animals were followed up for 10 weeks using serial cardiac magnetic resonance imaging to assess functional and structural remodeling (left ventricular ejection fraction (LVEF), systolic and diastolic volumes, and myocardial salvage index). Statistical comparisons were performed using Kruskal-Wallis and Mann-Whitney U tests. Biodistri-

bution analysis of 18F-FDG-labeled pCPC was also performed 4 h after infarction in a different subset of animals.

RESULTS Phenotypic and functional characterization of pCPC revealed a gene expression profile comparable to their human counterparts as well as preliminary functional equivalence. Left ventricular functional and structural remodeling showed significantly increased LVEF 10 weeks after IC administration of 50 M pCPC, associated to the recovery of left ventricular volumes that returned to pre-infarction values (LVEF at 10 weeks was 42.1 ± 10.0% in CON, 46.5 ± 7.4% in 25 M, and 50.2 ± 4.9% in 50 M, p < 0.05). Infarct remodeling was also improved following pCPC infusion with a significantly higher myocardial salvage index in both treated groups (0.35 ± 0.20 in CON; 0.61 ± 0.20, p = 0.04, in 25 M; and 0.63 ± 0.17, p = 0.01, in 50 M). Biodistribution studies demonstrated cardiac tropism 4 h after IC administration, with substantial myocardial retention of pCPC-associated tracer activity (18% of labeled cells in the heart), and no obstruction of coronary flow, indicating their suitability as a cell therapy product.

CONCLUSION IC administration of allogeneic pCPC at 1 week after acute myocardial infarction is feasible, safe, and associated with marked structural and functional benefit. The robust cardiac tropism of pCPC and the paracrine effects on left ventricle post-infarction remodeling established the preclinical bases for the CAREMI clinical trial (NCT02439398).

ABSTRACT 19

Non-invasive myocardial performance mapping using 3D echocardiographic stress-strain loops.

Pedrosa J, Duchenne J, Gheysens O, et al. Physics in Medicine and Biology, 2019, 64(11), 115026

INTRODUCTION/BACKGROUND Regional contribution to left ventricular (LV) ejection is of much clinical importance but its assessment is notably challenging. While deformation imaging is often used, this does not take into account loading conditions. Recently, a method for intraventricular pressure estimation was proposed, thus allowing for loading conditions to be taken into account in a non-invasive way. In this work, a method for 3D automatic myocardial performance mapping in echocardiography is proposed by performing 3D myocardial segmentation and tracking, thus giving access to local geometry and strain. This is then used to assess local LV stress-strain relationships which can be seen as a measure of local myocardial work. The proposed method was validated against 18F-fluorodeoxyglucose positron emission tomography, the reference method to clinically assess local metabolism. Averaged over all patients, the mean correlation between FDG-PET and the proposed method was. In conclusion, stress-strain loops were, for the first time, estimated from 3D echocardiography and correlated to the clinical gold standard for local metabolism, showing the future potential of real-time 3D echocardiography (RT3DE) for the assessment of local metabolic activity of the heart.

ABSTRACT 20

Role of interim and end of treatment positron emission tomography for response assessment and prediction of relapse in posttransplant lymphoproliferative disorder.

Van Keerberghen C, Goffin K, Gheysens O, et al. Acta Oncology, 2019, 58(7), 1041-1047

INTRODUCTION/BACKGROUND Fluorine-18-fluorodeoxyglucose positron emission tomography (PET) has an established and central role in diagnosis, staging and response evaluation of lymphoproliferative diseases. It has shown a high sensitivity and specificity at diagnosis in posttransplant lymphoproliferative disorders (PTLDs). However, little is known about the performance of interim and end of treatment (EOT) PET in PTLD patients with regards to response assessment, relapse prediction and outcome.

MATERIALS/METHODS We performed a single-center retrospective study in which we analyzed consecutive patients diagnosed with CD20-positive PTLD after solid organ transplantation between 2008 and 2017, who all received risk-stratified sequential treatment according to the PTLD-1 phase II trial. Interim and EOT PET studies were scored according to the Deauville criteria.

RESULTS Forty-one patients were included with median follow-up of 41.5 months (range 1-108). Positive and negative predictive values for disease recurrence were 13% and 85% for interim and 33% and 87% for EOT PET, respectively. There was no significant difference in overall survival, progression-free survival nor time to progression between negative versus positive patients on interim and EOT scans.

CONCLUSION Negative interim and/or negative end of treatment PET identify PTLD patients with low risk of disease recurrence.

ABSTRACT 21

Left ventricular remodeling results in homogenization of myocardial work distribution.

Duchenne J, Turco A, Gheysens O, et al. Circulation: Arrhytmia and Electrophysiology, 2019, 12(5), e007224

INTRODUCTION/BACKGROUND The interaction between regional left ventricular (LV) myocardial work and metabolism in remodeled hearts has not yet been well established. Our aim was to investigate the effect of inhomogeneous LV work distribution on regional metabolism and remodeling in our animal model with reversible dyssynchrony due to pacing.

MATERIALS/METHODS In 12 sheep, 8 weeks of right atrial and right ventricular free wall (DDD) pacing lead to LV dilatation, a thinned septum, and thickened lateral wall. Left bundle branch block-like dyssynchrony caused by DDD pacing could be acutely reverted by right atrial pacing (AAI) only. Invasive hemodynamics and echocardiography were used to assess regional work by stress-strain loop area and compared with regional glucose metabolism measured by 18F-fluorodeoxyglucose positron emission tomography with and without improved spatial resolution by motion and anatomy correction on gated reconstructions.

RESULTS Glucose metabolism by positron emission tomography with anatomic correction on gated positron emission tomography reconstruction showed a different regional distribution than with clinical reconstructions and correlated best and significantly with regional myocardial work. At baseline, work was homogeneously distributed with normal conduction (AAI pacing), whereas during dyssynchrony (DDD pacing), the lateral wall was more loaded, and the septum was unloaded. After 8 weeks of remodeling under DDD pacing, however, an almost homogeneous work distribution was found with DDD pacing, whereas with AAI pacing, the thin septum showed exaggerated loading and the lateral walls a low load. Our experimental observations were confirmed in 5 patient responders to cardiac resynchronization therapy. CONCLUSION Regional LV glucose metabolism closely correlates with regional work. Our data indicate that regionally different LV remodeling after exposure to inhomogeneous loading conditions, such as during LV dyssynchrony, is an adaptive process that helps to equilibrate work distribution. Correction of the inhomogeneous loading conditions, such as during cardiac resynchronization therapy, then triggers a reverse LV remodeling through the same mechanism.

ABSTRACT 22

Consensus document for the diagnosis of prosthetic joint infections: a joint paper by the EANM, EBJIS, and ESR (with ESCMID endorsement).

Signore A, Sconfienza LM, sGheysens O, et al. European Journal of Nuclear Medicine and Molecular Imaging, 2019, 46(4), 971-988

INTRODUCTION/BACKGROUND For the diagnosis of prosthetic joint infection, real evidence-based guidelines to aid clinicians in choosing the most accurate diagnostic strategy are lacking.

OBJECTIVE To address this need, we performed a multidisciplinary systematic review of relevant nuclear medicine, radiological, orthopaedic, infectious, and microbiological literature to define the diagnostic accuracy of each diagnostic technique and to address and provide evidence-based answers on uniform statements for each topic that was found to be important to develop a commonly agreed upon diagnostic flowchart.

RESULTS The approach used to prepare this set of multidisciplinary guidelines was to define statements of interest and follow the procedure indicated by the Oxford Centre for Evidence-based Medicine (OCEBM).

ABSTRACT 23

Local pulmonary drug delivery in the preterm rabbit: feasibility and efficacy of daily intratracheal injections.

Salaets T, Gie A, Gheysens O, et al. American Journal of Physiology - Lung Cellular and Molecular Physiology, 2019, 316(4), L589-L597

INTRODUCTION/BACKGROUND Recent clinical trials in newborns have successfully used surfactant as a drug carrier for an active compound, to minimize systemic exposure. To investigate the translational potential of surfactant-compound mixtures and other local therapeutics, a relevant animal model is required in which intratracheal administration for maximal local deposition is technically possible and well tolerated. Preterm rabbit pups (born at 28 days of gestation) were exposed to either hyperoxia or normoxia and randomized to receive daily intratracheal surfactant, daily intratracheal saline, or no injections for 7 days. At day 7, the overall lung function and morphology were assessed. Efficacy in terms of distribution was assessed by micro-PET-CT on both day 0 and day 7. Lung function as well as parenchymal and vascular structure were altered by hyperoxia, thereby reproducing a phenotype reminiscent of bronchopulmonary dysplasia (BPD). Neither intratracheal surfactant nor saline affected the survival or the hyperoxia-induced BPD phenotype of the pups. Using PET-CT, we demonstrate that 82.5% of the injected radioactive tracer goes and remains in the lungs, with a decrease of only 4% after 150 min. Surfactant and saline can safely and effectively be administered in spontaneously breathing preterm rabbits. The described model and method enable researchers to evaluate intratracheal pharmacological interventions for the treatment of BPD.

ABSTRACT 24

Consensus document for the diagnosis of peripheral bone infection in adults: a joint paper by the EANM, EBJIS, and ESR (with ESCMID endorsement).

Glaudemans AWJM, Jutte PC, Gheysens O, et al. European Journal of Nuclear Medicine and Molecular Imaging, 2019, 46(4), 957-970

INTRODUCTION/BACKGROUND In adults with a suspicion of peripheral bone infection, evidence-based guidelines in choosing the most accurate diagnostic strategy are lacking.

OBJECTIVE To provide an evidence-based, multidisciplinary consensus document on the diagnostic management of adult patients with PBIs, we performed a systematic review of relevant infectious, microbiological, orthopedic, radiological, and nuclear medicine literature. Delegates from four European societies (European Bone and Joint Infection Society, European Society of Microbiology and Infectious Diseases, European Society or Radiology, and European Association of Nuclear Medicine) defined clinical questions to be addressed, thoroughly reviewed the literature pertinent to each of the questions, and thereby evaluated the diagnostic accuracy of each diagnostic technique. Inclusion of the papers per statement was based on a PICO (Population/problem - Intervention/indicator - Comparator - Outcome) question following the strategy reported by the Oxford Centre for Evidence-based Medicine. For each statement, the level of evidence was graded according to the 2011 review of the Oxford Centre for Evidence-based Medicine. All approved statements were addressed taking into consideration the available diagnostic procedures, patient acceptance, tolerability, complications, and costs in Europe. Finally, a commonly agreed-upon diagnostic flowchart was developed.

ABSTRACT 25

Voriconazole-induced periostitis after allogeneic stem cell transplantation.

Haemels M, Pans S, Gheysens O, et al. Clinical Nuclear Medicine, 2019, 44(2), 159-160

INTRODUCTION/BACKGROUND A 34-year-old man with history of Hodgkin lymphoma presented 7 months after allogeneic stem cell transplantation with an unexplained severe musculoskeletal pain syndrome. A Tc-MDP bone SPECTCT showed multiple foci with moderate to intense bone uptake across the axial and appendicular skeleton consistent with periostitis. The patient had been on voriconazole daily for 4 months to treat an Aspergillus pneumonia, and in the absence of other causes, a drug-induced periostitis was suspected. Voriconazole was changed to posaconazole with complete resolution of the musculoskeletal symptoms within 3 weeks.