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See detail18F-FDG PET/CT imaging in rectal cancer: relationship with the RAS mutational status.
LOVINFOSSE, Pierre ULg; KOOPMANSCH, Benjamin ULg; LAMBERT, Frédéric ULg et al

in British Journal of Radiology (2016)

OBJECTIVE: Treating metastatic colorectal cancer with anti-EGFR monoclonal antibodies is recommended only for patients whose tumour does not harbour mutations of KRAS or NRAS. The aim of this study was to ... [more ▼]

OBJECTIVE: Treating metastatic colorectal cancer with anti-EGFR monoclonal antibodies is recommended only for patients whose tumour does not harbour mutations of KRAS or NRAS. The aim of this study was to investigate the biology of rectal cancers and specifically to evaluate the relationship between fluorine-18 fludeoxyglucose (18F-FDG) positron emission tomography (PET) intensity and heterogeneity parameters and their mutational status. METHODS: 151 patients with newly diagnosed rectal cancer were included in this retrospective study. All patients underwent a baseline 18F-FDG PET/CT within a median time interval of 27 days of tumour tissue sampling, which was performed before any treatment. Standardized uptake values (SUVs), volume-based parameters and texture analysis were studied. We retrospectively performed KRAS genotyping on codons 12, 13, 61, 117 and 146, NRAS genotyping on codons 12, 13 and 61 and BRAF on codon 600. Associations between PET/CT parameters and the mutational status were assessed using univariate and multivariate analysis. RESULTS: 83 (55%) patients had an RAS mutation: 74 KRAS and 9 NRAS, while 68 patients had no mutation (wild-type tumours). No patient had BRAF mutation. First-order features based on intensity histogram analysis were significantly associated with RAS mutations: maximum SUV (SUVmax) (p-value = 0.002), mean SUV (p-value = 0.006), skewness (p-value = 0.049), SUV standard deviation (p-value = 0.001) and SUV coefficient of variation (SUVcov) (p-value = 0.001). Both SUVcov and SUVmax showed an area under the curve of 0.65 with sensitivity of 56% and 69%, respectively, and specificity of 64% and 52%, respectively. None of the volume-based (metabolic tumour volume and total lesion glycolysis), nor local or regional textural features were associated with the presence of RAS mutations. CONCLUSION: Although rectal cancers with KRAS or NRAS mutations display a significantly higher glucose metabolism than wild-type cancers, the accuracy of the currently proposed quantitative metrics extracted from 18F-FDG PET/CT is not sufficiently high for playing a meaningful clinical role. ADVANCES IN KNOWLEDGE: RAS-mutated rectal cancers have a significantly higher glucose metabolism. However, the accuracy of 18F-FDG PET/CT quantitative metrics is not as such as the technique could play a clinical role. [less ▲]

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See detailHow to scan who: the delicate balance between selecting the patient and selecting the imaging protocol.
Hustinx, Roland ULg

in European Journal of Nuclear Medicine and Molecular Imaging (2016)

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See detail[18F]FPRGD2 PET/CT imaging of integrin αvβ3 levels in patients with locally advanced rectal carcinoma
WITHOFS, Nadia ULg; Martinive, Philippe ULg; VANDERICK, Jean ULg et al

in European journal of nuclear medicine and molecular imaging (2016)

PURPOSE: Our primary objective was to determine if [18F]FPRGD2 PET/CT performed at baseline and/or after chemoradiotherapy (CRT) could predict tumour regression grade (TRG) in locally advanced rectal ... [more ▼]

PURPOSE: Our primary objective was to determine if [18F]FPRGD2 PET/CT performed at baseline and/or after chemoradiotherapy (CRT) could predict tumour regression grade (TRG) in locally advanced rectal cancer (LARC). Secondary objectives were to compare baseline [18F]FPRGD2 and [18F]FDG uptake, to evaluate the correlation between posttreatment [18F]FPRGD2 uptake and tumour microvessel density (MVD) and to determine if [18F]FPRGD2 and FDG PET/CT could predict disease-free survival. METHODS: Baseline [18F]FPRGD2 and FDG PET/CT were performed in 32 consecutive patients (23 men, 9 women; mean age 63 +/- 8 years) with LARC before starting any therapy. A posttreatment [18F]FPRGD2 PET/CT scan was performed in 24 patients after the end of CRT (median interval 7 weeks, range 3 - 15 weeks) and before surgery (median interval 4 days, range 1 - 15 days). RESULTS: All LARC showed uptake of both [18F]FPRGD2 (SUVmax 5.4 +/- 1.5, range 2.7 - 9) and FDG (SUVmax 16.5 +/- 8, range 7.1 - 36.5). There was a moderate positive correlation between [18F]FPRGD2 and FDG SUVmax (Pearson's r = 0.49, p = 0.0026). There was a moderate negative correlation between baseline [18F]FPRGD2 SUVmax and the TRG (Spearman's r = -0.37, p = 0.037), and a [18F]FPRGD2 SUVmax of >5.6 identified all patients with a complete response (TRG 0; AUC 0.84, 95 % CI 0.68 - 1, p = 0.029). In the 24 patients who underwent a posttreatment [18F]FPRGD2 PET/CT scan the response index, calculated as [(SUVmax1 - SUVmax2)/SUVmax1] x 100 %, was not associated with TRG. Post-treatment [18F]FPRGD2 uptake was not correlated with tumour MVD. Neither [18F]FPRGD2 nor FDG uptake predicted disease-free survival. CONCLUSION: Baseline [18F]FPRGD2 uptake was correlated with the pathological response in patients with LARC treated with CRT. However, the specificity was too low to consider its clinical routine use. [less ▲]

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See detailFDG PET/CT texture analysis for predicting the outcome of lung cancer treated by stereotactic body radiation therapy.
LOVINFOSSE, Pierre ULg; Janvary, Zsolt Levente; COUCKE, Philippe ULg et al

in European journal of nuclear medicine and molecular imaging (2016)

INTRODUCTION: With 18F-FDG PET/CT, tumor uptake intensity and heterogeneity have been associated with outcome in several cancers. This study aimed at investigating whether 18F-FDG uptake intensity, volume ... [more ▼]

INTRODUCTION: With 18F-FDG PET/CT, tumor uptake intensity and heterogeneity have been associated with outcome in several cancers. This study aimed at investigating whether 18F-FDG uptake intensity, volume or heterogeneity could predict the outcome in patients with non-small cell lung cancers (NSCLC) treated by stereotactic body radiation therapy (SBRT). METHODS: Sixty-three patients with NSCLC treated by SBRT underwent a 18F-FDG PET/CT before treatment. Maximum and mean standard uptake value (SUVmax and SUVmean), metabolic tumoral volume (MTV), total lesion glycolysis (TLG), as well as 13 global, local and regional textural features were analysed. The predictive value of these parameters, along with clinical features, was assessed using univariate and multivariate analysis for overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS). Cutoff values were obtained using logistic regression analysis, and survivals were compared using Kaplan-Meier analysis. RESULTS: The median follow-up period was 27.1 months for the entire cohort and 32.1 months for the surviving patients. At the end of the study, 25 patients had local and/or distant recurrence including 12 who died because of the cancer progression. None of the clinical variables was predictive of the outcome, except age, which was associated with DFS (HR 1.1, P = 0.002). None of the 18F-FDG PET/CT or clinical parameters, except gender, were associated with OS. The univariate analysis showed that only dissimilarity (D) was associated with DSS (HR = 0.822, P = 0.037), and that several metabolic measurements were associated with DFS. In multivariate analysis, only dissimilarity was significantly associated with DSS (HR = 0.822, P = 0.037) and with DFS (HR = 0.834, P < 0.01). CONCLUSION: The textural feature dissimilarity measured on the baseline 18F-FDG PET/CT appears to be a strong independent predictor of the outcome in patients with NSCLC treated by SBRT. This may help selecting patients who may benefit from closer monitoring and therapeutic optimization. [less ▲]

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See detail18FDG-PET/CT IMAGING IN SUSPECTED ACUTE RENAL ALLOGRAFT REJECTION
LOVINFOSSE, Pierre ULg; WEEKERS, Laurent ULg; BOVY, Christophe ULg et al

Conference (2015, September 13)

The diagnosis procedure for kidney transplant recipients (KTR) with suspected acute rejection (AR) relies on needle biopsy. Noninvasive tests to predict nonrejection would be preferable. AR is associated ... [more ▼]

The diagnosis procedure for kidney transplant recipients (KTR) with suspected acute rejection (AR) relies on needle biopsy. Noninvasive tests to predict nonrejection would be preferable. AR is associated with a recruitment of activated leukocytes into the transplant, which are characterized by a high metabolic activity and an increased uptake of glucose analog, Fluoro-deoxyglucose ( FDG). Thus, FDG-Positron emission tomography coupled with computed tomography (PET/CT) may help noninvasively distinguish nonrejection from AR. From January 2013 to February 2015, we prospectively performed 32 FDGPET/ CT in 31 adult KTR with suspected renal AR who underwent a biopsy. Biopsies were categorized as “normal”, “borderline”, “AR” or “others” according to Banff classification. PET/CT imaging was performed within 201 ± 18 minutes after i.v. administration of 3.2 ± 0.2 MBq/kg of FDG, before any modification of immunosuppression. The mean standard uptake values (SUV) of both upper and lower renal poles were measured, with no threshold activity. Biopsies were diagnosed as “normal”, “borderline”, “AR” or “others” in 8, 10, 8 and 6 (including 3 polyoma-BK nephropathies) cases. Mean SUV respectively reached 1.5 ± 0.2, 1.6 ± 0.3, 2.9 ± 0.8, 2.2 ± 1.2 in each category. Mean SUV of biopsy-proven AR was significantly higher than “normal” cases (p<0.01). No difference was found between “normal” vs. “borderline”, or between “AR” vs. “others” histopathology. Still, a positive correlation between mean SUV and acute composite (g+i+t+v+ptc) Banff score was found, with a coefficient of 0.70 (p<0.001). Sensitivity and specificity of FDG-PET/CT in detecting pathological biospies were respectively 92.3% and 36.8%, with a mean SUV threshold at 1.4. FDG-PET/CT imaging may help discriminate nonrejection, thereby avoiding unnecessary transplant biopsy in KTR with suspected AR. [less ▲]

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See detailRecovery of language comprehension in the minimally conscious state studied by FDG-PET
Wannez, Sarah ULg; Thibaut, Aurore ULg; Vitali-Roscini, Gaia et al

Poster (2015, June 21)

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See detailImagerie métabolique en oncologie thoracique
DUYSINX, Bernard ULg; HUSTINX, Roland ULg

in EMC Pneumologie (2015), 12(2),

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See detailPrognostic value of (18)F-FDG PET/CT in liver transplantation for hepatocarcinoma.
Detry, Olivier ULg; Govaerts, Laurence; De Roover, Arnaud ULg et al

in World journal of gastroenterology : WJG (2015), 21(10), 3049-54

AIM: To evaluate the prognostic value of pretreatment FDG positron emission tomography computed tomography (PET-CT) in patients with hepatocarcinoma treated by liver transplantation (LT). METHODS: The ... [more ▼]

AIM: To evaluate the prognostic value of pretreatment FDG positron emission tomography computed tomography (PET-CT) in patients with hepatocarcinoma treated by liver transplantation (LT). METHODS: The authors retrospectively analyzed the data of 27 patients (mean age 58 +/- 9 years) who underwent FDG PET-CT before LT for hepatocarcinoma. Mean follow-up was 26 +/- 18 mo. The FDG PET/CT was performed according to a standard clinical protocol: 4 MBqFDG/kg body weight, uptake 60 min, low-dose non-enhanced CT. The authors measured the SUVmax and SUVmean of the tumor and the normal liver. The tumor/liver activity ratios (RSUVmax and RSUVmean) were tested as prognostic factors and compared to the following conventional prognostic factors: MILAN, CLIP, OKUDA, TNM stage, alphafoetoprotein level, portal thrombosis, size of the largest nodule, tumor differentiation, microvascular invasion, underlying cirrhosis and liver function. RESULTS: Overall and recurrence free survivals were 80.7% and 67.4% at 3 years, and 70.6% and 67.4% at 5 years, respectively. According to a multivariate Cox model, only FDG PET/CT RSUVmax predicted recurrence free survival. Even though the MILAN criteria alone were not predictive, it is worth noting that none of the patients outside the MILAN criteria and with RSUVmax < 1.15 relapsed. CONCLUSION: FDG PET/CT with an RSUVmax cut-off value of 1.15 is a strong prognostic factor for recurrence and death in patients with HCC treated by LT in this retrospective series. Further prospective studies should test whether this metabolic index should be systematically included in the preoperative assessment. [less ▲]

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See detail18F-FPRGD2 PET/CT imaging of integrin αvβ3 in renal carcinomas: Correlation with histopathology
WITHOFS, Nadia ULg; SIGNOLLE, NICOLAS; SOMJA, Joan ULg et al

in Journal of Nuclear Medicine (The) (2015)

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See detailChallenges for imaging and therapy of musculoskeletal tumours
COOK, GARY; HUSTINX, Roland ULg

in Clinical and Translational Imaging (2015)

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See detailBiodistribution and radiation dosimetry for the novel SV2A radiotracer [18F]UCB-H: First-in-human study.
Bretin, Florian ULg; Bahri, Mohamed Ali ULg; BERNARD, Claire ULg et al

in Molecular Imaging & Biology (2015), 17

Abstract- [18F]UCB-H is a novel radiotracer with a high affinity for SV2A, a protein expressed in synaptic vesicles. SV2A is the binding site of levetiracetam, a “first in class” antiepileptic drug with a ... [more ▼]

Abstract- [18F]UCB-H is a novel radiotracer with a high affinity for SV2A, a protein expressed in synaptic vesicles. SV2A is the binding site of levetiracetam, a “first in class” antiepileptic drug with a distinct but still poorly understood mechanism of action. The objective of this study was to determine the biodistribution and radiation dosimetry of [18F]UCB-H in a human clinical trial and to establish injection limits according to biomedical research guidelines. Additionally, the clinical radiation dosimetry results were compared to estimations in previously published preclinical data. Dynamic whole body PET/CT imaging was performed over approximately 110 minutes on five healthy male volunteers after injection of 144.5 ± 7.1 MBq (range, 139.1 – 156.5 MBq) of [18F]UCB-H. Major organs were delineated on CT images and time-activity curves were obtained from co-registered dynamic PET emission scans. Time-integrated activity coefficients were calculated as area under the curve using trapezoidal numerical integration. Urinary excretion data based on PET-activities including voiding was simulated using the dynamic bladder module of OLINDA/EXM. The radiation dosimetry was calculated using OLINDA/EXM. The effective dose to the OLINDA/EXM 70 kg standard male was 1.54E-02 ± 6.84E-04 mSv/MBq, with urinary bladder wall, gallbladder wall and the liver receiving the highest absorbed dose. The brain, the tracer’s main organ of interest, received an absorbed dose of 1.89E-02 ± 2.32E-03 mGy/MBq. This first human dosimetry study of [18F]UCB-H indicated that the tracer shows similar radiation burdens to widely used common clinical tracers. Single injections of at maximum 672 MBq for USA practice and 649 MBq for European practice keep radiation exposure below recommended limits. Recently published preclinical dosimetry data extrapolated from mice provided satisfactory prediction of total body and effective dose, but showed significant differences in organ absorbed doses compared to human data. [less ▲]

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See detail(Tissue PET) vascularmetabolic imaging and peripheral plasma biomarkers in the evolution of chronic aortic dissections
SAKALIHASAN, Natzi ULg; NIENABER, Christoph; HUSTINX, Roland ULg et al

in European Heart Journal - Cardiovascular Imaging (2015)

Enhanced FDG uptake may be considered as a complementary imaging marker associated with secondary complications in type B dissections. During follow-up, aneurysmal progression is related to PET/CT and ... [more ▼]

Enhanced FDG uptake may be considered as a complementary imaging marker associated with secondary complications in type B dissections. During follow-up, aneurysmal progression is related to PET/CT and biomarkers of thrombus renewal and lysis. [less ▲]

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See detail18F-FDG PET Uptake Characterization Through Texture Analysis: Investigating the Complementary Nature of Heterogeneite and Functional Tumor Volume in a Multi-Cancer Site Patient Cohort
HATT, MAT; MAJDOUB, MOHAMED; VALLIERES, MARTIN et al

in Journal of Nuclear Medicine (The) (2015), 56(1), 38-44

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See detailCirculating miRNA signature of PET-positive abdominal aortic aneurysms: new potential predictors of rupture
Courtois, Audrey ULg; Nusgens, Betty ULg; HUSTINX, Roland ULg et al

in Atherosclerosis, Thrombosis and Vascular Biology (2015)

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See detail18F-FDG PET/CT in the Management of Aortitis.
Bruls, Samuel; Courtois, Audrey ULg; Nusgens, Betty ULg et al

in Clinical nuclear medicine (2015)

BACKGROUND: Aortitis is a generic term defined as an inflammatory condition involving the aortic wall, of infectious or noninfectious origin. This inflammatory process may deteriorate the aortic wall ... [more ▼]

BACKGROUND: Aortitis is a generic term defined as an inflammatory condition involving the aortic wall, of infectious or noninfectious origin. This inflammatory process may deteriorate the aortic wall, resulting in potentially life-threatening vascular complications. Therefore, it is important to establish a diagnosis as early as possible. PATIENTS AND METHODS: During a 4-year period, 428 consecutive patients referred to our department for aortic diseases underwent FDG PET/CT examinations. Among these, 18 patients (4.2%) were suspected to have aortitis. All of them had an initial positive FDG PET/CT uptake occurring in the aorta and major branches as evaluated by visual analysis of images and assessed with the final diagnosis of aortitis. During follow-up, after surgery and/or upon immunosuppressive treatment, each of these patients underwent a second PET/CT that was compared with the initial evaluation. In all cases, normalization of FDG uptake was correlated with clinical improvement. CONCLUSIONS: Our study aimed to illustrate the potential clinical value of functional monitoring with PET/CT in the management of aortitis. FDG PET/CT constitutes a valuable imaging modality to establish an early diagnosis, monitor disease progression and treatment, and evaluate vascular complication and relapse. We highlight the importance of an early detection of inflammatory large-vessel pathology, which may represent a major threat. [less ▲]

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See detailGene Expression Study in Positron Emission Tomography–Positive Abdominal Aortic Aneurysms Identifies CCL18 as a Potential Biomarker for Rupture Risk
Courtois, Audrey ULg; Nusgens, Betty ULg; HUSTINX, Roland ULg et al

in Molecular Medicine (2015)

Rupture of abdominal aortic aneurysm (AAA) is a cause of significant mortality and morbidity in ageing populations. Uptake of 18-fluorodeoxyglucose (FDG) detected by positron emission tomography (PET) is ... [more ▼]

Rupture of abdominal aortic aneurysm (AAA) is a cause of significant mortality and morbidity in ageing populations. Uptake of 18-fluorodeoxyglucose (FDG) detected by positron emission tomography (PET) is observed in the wall of 12% of AAA (A+), most of them being symptomatic. We previously showed that the metabolically active areas displayed adventitial inflammation, medial degeneration and molecular alterations prefacing wall rupture. The aim of this study was to identify new factors predictive of rupture.Transcriptomic analyses were performed in the media and adventitia layers from three types of samples: AAA without (A0) and with FDG uptake (A+), both at the positive spot (A+Pos) and at a paired distant negative site (A+Neg) of the same aneurysm. Follow-up studies included RT-PCR, immunohistochemical staining and ELISA. A large number of genes, including matrix metalloproteinases, collagens and cytokines as well as genes involved in osteochondral development, were differentially expressed in the A+Pos as compared to A+Neg. Moreover, a series of genes, notably CCL18, was differentially expressed both in the A+Neg and A+Pos as compared to the A0. A significant increase of CCL18 was also found at the protein level in the aortic wall and in peripheral blood of A+ patients as compared to A0.In conclusion, new factors, including CCL18, involved in the progression of AAA and, potentially, in their rupture were identified by a genome-wide analysis of PET-positive and negative human aortic tissue samples. Further work is needed to study their role in AAA destabilization and weakening. [less ▲]

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See detailA theranostic tool for Hepatocellular carcinoma: the Starch-Based Microparticles
Verger, Elise ULg; Cikankowitz, Annabelle; Bouvier, Antoine et al

Conference (2015)

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See detailClinical Response to tDCS Depends on Residual Brain Metabolism and Grey Matter Integrity in Patients With Minimally Conscious State.
Thibaut, Aurore ULg; Di Perri, Carol; Chatelle, Camille ULg et al

in Brain stimulation (2015), 8(6), 1116-23

BACKGROUND: Transcranial direct current stimulation (tDCS) was recently shown to promote recovery of voluntary signs of consciousness in some patients in minimally conscious state (MCS). However, it ... [more ▼]

BACKGROUND: Transcranial direct current stimulation (tDCS) was recently shown to promote recovery of voluntary signs of consciousness in some patients in minimally conscious state (MCS). However, it remains unclear why clinical improvement is only observed in a subgroup of patients. OBJECTIVES: In this retrospective study, we investigated the relationship between tDCS responsiveness and neuroimaging data from MCS patients. METHODS: Structural Magnetic Resonance Imaging (MRI), Fluorodeoxyglucose Positron emission tomography (FDG-PET) and clinical electroencephalography (EEG) were acquired in 21 sub-acute and chronic MCS patients (8 tDCS responders) who subsequently (<48 h) received left dorsolateral prefrontal (DLPF) tDCS in a double-blind randomized cross-over trial. The behavioral data have been published elsewhere (Thibaut et al., Neurology, 2014). RESULTS: Grey matter atrophy was observed in non-responders as compared with responders in the left DLPF cortex, the medial-prefrontal cortex, the cingulate cortex, the hippocampi, part of the rolandic regions, and the left thalamus. FDG-PET showed hypometabolism in non-responders as compared with responders in the left DLPF cortex, the medial-prefrontal cortex, the precuneus, and the thalamus. EEG did not show any difference between the two groups. CONCLUSION: Our findings suggest that the transient increase of signs of consciousness following left DLPF tDCS in patients in MCS require grey matter preservation and residual metabolic activity in cortical and subcortical brain areas known to be involved in attention and working memory. These results further underline the critical role of long-range cortico-thalamic connections in consciousness recovery, providing important information for guidelines on the use of tDCS in disorders of consciousness. [less ▲]

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