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Article: Introducing HDAC-Targeting Radiopharmaceuticals for Glioblastoma Imaging and Therapy.

Everix, Liesbeth / Seane, Elsie Neo / Ebenhan, Thomas / Goethals, Ingeborg / Bolcaen, Julie

2023 Volume 16, Issue 2

Abstract: Despite recent advances in multimodality therapy for glioblastoma (GB) incorporating surgery, radiotherapy, chemotherapy and targeted therapy, the overall prognosis remains poor. One of the interesting targets for GB therapy is the histone deacetylase ... ...

Abstract	Despite recent advances in multimodality therapy for glioblastoma (GB) incorporating surgery, radiotherapy, chemotherapy and targeted therapy, the overall prognosis remains poor. One of the interesting targets for GB therapy is the histone deacetylase family (HDAC). Due to their pleiotropic effects on, e.g., DNA repair, cell proliferation, differentiation, apoptosis and cell cycle, HDAC inhibitors have gained a lot of attention in the last decade as anti-cancer agents. Despite their known underlying mechanism, their therapeutic activity is not well-defined. In this review, an extensive overview is given of the current status of HDAC inhibitors for GB therapy, followed by an overview of current HDAC-targeting radiopharmaceuticals. Imaging HDAC expression or activity could provide key insights regarding the role of HDAC enzymes in gliomagenesis, thus identifying patients likely to benefit from HDACi-targeted therapy.
Language	English
Publishing date	2023-02-01
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2193542-7
ISSN	1424-8247
ISSN	1424-8247
DOI	10.3390/ph16020227
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Article ; Online: Comparison of an in-house acquired brain F-18 FDG PET normal database with commercially available normal data.

Waterschoot, Robbe / D'Asseler, Yves / Goethals, Ingeborg

Nuclear medicine communications

2021 Volume 42, Issue 9, Page(s) 1039–1044

Abstract: Introduction: Current guidelines recommend the use of semiautomated assessment of F-18 FDG PET brain studies. Accuracy is influenced by the normal data, which requires knowledge of the included subjects and how they were acquired. Due to confidentiality, ...

Abstract	Introduction: Current guidelines recommend the use of semiautomated assessment of F-18 FDG PET brain studies. Accuracy is influenced by the normal data, which requires knowledge of the included subjects and how they were acquired. Due to confidentiality, such information is often not completely disclosed. Our aim was to determine the variation in FDG uptake between several commercially available and our in-house normal database. Methods: Our database contains 83 healthy subjects. Outlier detection using SPM further ensured normality, resulting in exclusion of three subjects. The remaining 80 subjects were analyzed using three commercially available software packages. Z-score data per patient and per lobe were extracted and pooled in predefined age groups (18-40, 41-60 and 61-80 years old) with a calculation of mean Z-scores and SD. Correlation between Z-score output of different software was investigated. Results: In the 18-40 years age group, frontotemporal hypermetabolism was found with all software. Decreased cerebellar uptake was found with two software packages. Mean Z-scores are closer to zero in the 41-60 years age group compared to the younger group, and mostly within the normal range in the 61-80 years age group with all software. A moderate to high linear correlation between Z-score output was found, but individual Z-scores varied widely. Conclusions: The three software packages yielded varying Z-score output, partially explained by an age mismatch between our subjects and subjects in their normal databases. A definitive explanation for the remaining differences is lacking. This emphasizes the importance of age-matched normal data and knowledge of the included databases to allow adequate preprocessing.
MeSH term(s)	Adolescent ; Aged ; Aged, 80 and over ; Fluorodeoxyglucose F18 ; Humans ; Image Processing, Computer-Assisted ; Middle Aged ; Positron-Emission Tomography
Chemical Substances	Fluorodeoxyglucose F18 (0Z5B2CJX4D)
Language	English
Publishing date	2021-04-13
Publishing country	England
Document type	Journal Article
ZDB-ID	758141-5
ISSN	1473-5628 ; 0143-3636
ISSN (online)	1473-5628
ISSN	0143-3636
DOI	10.1097/MNM.0000000000001427
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Zs.A 1577: Show issues

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Article ; Online: Magnetic resonance imaging-guided radiation therapy using animal models of glioblastoma.

Vanhove, Christian / Goethals, Ingeborg

The British journal of radiology

2019 Volume 92, Issue 1095, Page(s) 20180713

Abstract: Glioblastoma is the most aggressive and most common malignant primary brain tumour in adults and has a high mortality and morbidity. Because local tumour control in glioblastoma patients is still elusive in the majority of patients, there is an urgent ... ...

Abstract	Glioblastoma is the most aggressive and most common malignant primary brain tumour in adults and has a high mortality and morbidity. Because local tumour control in glioblastoma patients is still elusive in the majority of patients, there is an urgent need for alternative treatment strategies. However, to implement changes to the existing clinical standard of care, research must be conducted to develop alternative treatment strategies. A novel approach in radiotherapy is the introduction of pre-clinical precision image-guided radiation research platforms. The aim of this review is to give a brief overview of the efforts that have been made in the field of radiation research using animal models of glioblastoma. Because MRI has become the reference imaging technique for treatment planning and assessment of therapeutic responses in glioblastoma patients, we will focus in this review on small animal radiotherapy combined with MRI.
MeSH term(s)	Animals ; Brain Neoplasms/radiotherapy ; Disease Models, Animal ; Glioblastoma/radiotherapy ; Magnetic Resonance Imaging/methods ; Radiotherapy Planning, Computer-Assisted/methods ; Radiotherapy, Image-Guided/methods
Language	English
Publishing date	2019-01-17
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2982-8
ISSN	1748-880X ; 0007-1285
ISSN (online)	1748-880X
ISSN	0007-1285
DOI	10.1259/bjr.20180713
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Article: Cost-Effectiveness of [

Baguet, Tristan / Verhoeven, Jeroen / De Vos, Filip / Goethals, Ingeborg

Frontiers in oncology

2019 Volume 9, Page(s) 814

Abstract: Background and Purpose: ...

Abstract	Background and Purpose:
Language	English
Publishing date	2019-08-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2019.00814
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Article ; Online: Positron Emission Tomography-based Dose Painting Radiation Therapy in a Glioblastoma Rat Model using the Small Animal Radiation Research Platform.

Donche, Sam / Verhoeven, Jeroen / Descamps, Benedicte / Bouckaert, Charlotte / Raedt, Robrecht / Vanhove, Christian / Goethals, Ingeborg

Journal of visualized experiments : JoVE

2022 , Issue 181

Abstract: A rat glioblastoma model to mimic chemo-radiation treatment of human glioblastoma in the clinic was previously established. Similar to the clinical treatment, computed tomography (CT) and magnetic resonance imaging (MRI) were combined during the ... ...

Abstract	A rat glioblastoma model to mimic chemo-radiation treatment of human glioblastoma in the clinic was previously established. Similar to the clinical treatment, computed tomography (CT) and magnetic resonance imaging (MRI) were combined during the treatment-planning process. Positron emission tomography (PET) imaging was subsequently added to implement sub-volume boosting using a micro-irradiation system. However, combining three imaging modalities (CT, MRI, and PET) using a micro-irradiation system proved to be labor-intensive because multimodal imaging, treatment planning, and dose delivery have to be completed sequentially in the preclinical setting. This also results in a workflow that is more prone to human error. Therefore, a user-friendly algorithm to further optimize preclinical multimodal imaging-based radiation treatment planning was implemented. This software tool was used to evaluate the accuracy and efficiency of dose painting radiation therapy with micro-irradiation by using an in silico study design. The new methodology for dose painting radiation therapy is superior to the previously described method in terms of accuracy, time efficiency, and intra- and inter-user variability. It is also an important step towards the implementation of inverse treatment planning on micro-irradiators, where forward planning is still commonly used, in contrast to clinical systems.
MeSH term(s)	Animals ; Glioblastoma/diagnostic imaging ; Glioblastoma/pathology ; Glioblastoma/radiotherapy ; Magnetic Resonance Imaging/methods ; Multimodal Imaging/methods ; Positron-Emission Tomography/methods ; Radiotherapy Planning, Computer-Assisted/methods ; Rats ; Tomography, X-Ray Computed/methods
Language	English
Publishing date	2022-03-24
Publishing country	United States
Document type	Journal Article ; Video-Audio Media ; Research Support, Non-U.S. Gov't
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/62560
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Article ; Online: Disease Control and Late Toxicity in Adaptive Dose Painting by Numbers Versus Nonadaptive Radiation Therapy for Head and Neck Cancer: A Randomized Controlled Phase 2 Trial.

De Bruycker, Aurélie / De Neve, Wilfried / Daisne, Jean-François / Vercauteren, Tom / De Gersem, Werner / Olteanu, Luiza / Berwouts, Dieter / Deheneffe, Stéphanie / Madani, Indira / Goethals, Ingeborg / Duprez, Fréderic

International journal of radiation oncology, biology, physics

2024

Abstract: Purpose: Local recurrence remains the main cause of death in stage III-IV nonmetastatic head and neck cancer (HNC), with relapse-prone regions within high : Methods and materials: This 2-center randomized controlled phase 2 trial assigned (1:1) ... ...

Abstract	Purpose: Local recurrence remains the main cause of death in stage III-IV nonmetastatic head and neck cancer (HNC), with relapse-prone regions within high Methods and materials: This 2-center randomized controlled phase 2 trial assigned (1:1) patients to receive A-DPBN or S-IMRT (+/-chemotherapy). Eligibility: nonmetastatic HNC of oral cavity, oro-/hypopharynx, or larynx, needing radio(chemo)therapy; T1-4N0-3 (exception: T1-2N0 glottic); KPS ≥ 70; ≥18 years; and informed consent. Primary outcomes: 1-year LC and RC. The dose prescription for A-DPBN was intercurrently adapted in 2 steps to an absolute dose-volume limit (≤1.75 cm Results: Ninety-five patients were randomized (A-DPBN, 47; S-IMRT, 48). Median follow-up was 31 months (IQR, 14-48 months); 29 patients died (17 of cancer progression). A-DPBN resulted in superior LC compared with S-IMRT, with 1- and 2-year LC of 91% and 88% versus 78% and 75%, respectively (hazard ratio, 3.13; 95% CI, 1.13-8.71; P = .021). RC and overall survival were comparable between arms, as was overall grade (G) ≥3 late toxicity (36% vs 20%; P = .1). More ≥G3 late mucosal ulcers were observed in active smokers (29% vs 3%; P = .005) and alcohol users (33% vs 13%; P = .02), independent of treatment arm. Similarly, in the A-DPBN arm, significantly more patients who smoked at diagnosis developed ≥G3 (46% vs 12%; P = .005) and ≥G4 (29% vs 8%; P = .048) mucosal ulcers. One arterial blowout occurred after a G5 mucosal toxicity. Conclusions: A-DPBN resulted in superior 1- and 2-year LC for HNC compared with S-IMRT. This supports further exploration in multicenter phase 3 trials. It will, however, be challenging to recruit a substantial patient sample for such trials, as concerns have arisen regarding the association of late mucosal ulcers when escalating the dose in continuing smokers.
Language	English
Publishing date	2024-02-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	197614-x
ISSN	1879-355X ; 0360-3016
ISSN (online)	1879-355X
ISSN	0360-3016
DOI	10.1016/j.ijrobp.2024.01.012
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Article ; Online: Retrospective real-life study on preoperative imaging for minimally invasive parathyroidectomy in primary hyperparathyroidism.

Bijnens, Jacqueline / Van den Bruel, Annick / Vander Poorten, Vincent / Goethals, Ingeborg / Van Schandevyl, Steven / Dick, Catherine / De Geeter, Frank

Scientific reports

2022 Volume 12, Issue 1, Page(s) 17427

Abstract: The objective of this study was to retrospectively evaluate preoperative imaging modalities for localization of parathyroid adenomas with a view to enable minimally invasive parathyroidectomy and in particular, to consider the contribution ... ...

Abstract	The objective of this study was to retrospectively evaluate preoperative imaging modalities for localization of parathyroid adenomas with a view to enable minimally invasive parathyroidectomy and in particular, to consider the contribution of
MeSH term(s)	Humans ; Parathyroidectomy/methods ; Parathyroid Neoplasms/diagnostic imaging ; Parathyroid Neoplasms/surgery ; Hyperparathyroidism, Primary/diagnostic imaging ; Hyperparathyroidism, Primary/surgery ; Retrospective Studies ; Parathyroid Glands/surgery ; Positron Emission Tomography Computed Tomography ; Sodium Pertechnetate Tc 99m ; Technetium Tc 99m Sestamibi ; Tomography, Emission-Computed, Single-Photon ; Adenoma/diagnostic imaging ; Adenoma/surgery ; Radiopharmaceuticals
Chemical Substances	fluorocholine (6029HGL0QP) ; Sodium Pertechnetate Tc 99m (A0730CX801) ; Technetium Tc 99m Sestamibi (971Z4W1S09) ; fluoromethylcholine ; Radiopharmaceuticals
Language	English
Publishing date	2022-10-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-18219-3
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Article: Positron emission tomography-based dose painting radiation therapy in a glioblastoma rat model using the small animal radiation research platform

Donche, Sam / Verhoeven, Jeroen / Descamps, Benedicte / Bouckaert, Charlotte / Raedt, Robrecht / Vanhove, Christian / Goethals, Ingeborg

Journal of visualized experiments. 2022 Mar. 24, , no. 181

2022

Abstract	A rat glioblastoma model to mimic chemo-radiation treatment of human glioblastoma in the clinic was previously established. Similar to the clinical treatment, computed tomography (CT) and magnetic resonance imaging (MRI) were combined during the treatment-planning process. Positron emission tomography (PET) imaging was subsequently added to implement sub-volume boosting using a micro-irradiation system. However, combining three imaging modalities (CT, MRI, and PET) using a micro-irradiation system proved to be labor-intensive because multimodal imaging, treatment planning, and dose delivery have to be completed sequentially in the preclinical setting. This also results in a workflow that is more prone to human error. Therefore, a user-friendly algorithm to further optimize preclinical multimodal imaging-based radiation treatment planning was implemented. This software tool was used to evaluate the accuracy and efficiency of dose painting radiation therapy with micro-irradiation by using an in silico study design. The new methodology for dose painting radiation therapy is superior to the previously described method in terms of accuracy, time efficiency, and intra- and inter-user variability. It is also an important step towards the implementation of inverse treatment planning on micro-irradiators, where forward planning is still commonly used, in contrast to clinical systems.
Keywords	algorithms ; animal models ; computed tomography ; computer simulation ; computer software ; electrons ; experimental design ; glioblastoma ; humans ; magnetism ; positron-emission tomography ; radiotherapy ; rats
Language	English
Dates of publication	2022-0324
Size	p. e62560.
Publishing place	Journal of Visualized Experiments
Document type	Article
ZDB-ID	2259946-0
ISSN	1940-087X
ISSN	1940-087X
DOI	10.3791/62560
Database	NAL-Catalogue (AGRICOLA)

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Article: Perspective on the Use of DNA Repair Inhibitors as a Tool for Imaging and Radionuclide Therapy of Glioblastoma.

Everix, Liesbeth / Nair, Shankari / Driver, Cathryn H S / Goethals, Ingeborg / Sathekge, Mike M / Ebenhan, Thomas / Vandevoorde, Charlot / Bolcaen, Julie

Cancers

2022 Volume 14, Issue 7

Abstract: Despite numerous innovative treatment strategies, the treatment of glioblastoma (GB) remains challenging. With the current state-of-the-art therapy, most GB patients succumb after about a year. In the evolution of personalized medicine, targeted ... ...

Abstract	Despite numerous innovative treatment strategies, the treatment of glioblastoma (GB) remains challenging. With the current state-of-the-art therapy, most GB patients succumb after about a year. In the evolution of personalized medicine, targeted radionuclide therapy (TRT) is gaining momentum, for example, to stratify patients based on specific biomarkers. One of these biomarkers is deficiencies in DNA damage repair (DDR), which give rise to genomic instability and cancer initiation. However, these deficiencies also provide targets to specifically kill cancer cells following the synthetic lethality principle. This led to the increased interest in targeted drugs that inhibit essential DDR kinases (DDRi), of which multiple are undergoing clinical validation. In this review, the current status of DDRi for the treatment of GB is given for selected targets: ATM/ATR, CHK1/2, DNA-PK, and PARP. Furthermore, this review provides a perspective on the use of radiopharmaceuticals targeting these DDR kinases to (1) evaluate the DNA repair phenotype of GB before treatment decisions are made and (2) induce DNA damage via TRT. Finally, by applying in-house selection criteria and analyzing the structural characteristics of the DDRi, four drugs with the potential to become new therapeutic GB radiopharmaceuticals are suggested.
Language	English
Publishing date	2022-04-03
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14071821
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Article ; Online: Machine learning based brain tumour segmentation on limited data using local texture and abnormality.

Bonte, Stijn / Goethals, Ingeborg / Van Holen, Roel

Computers in biology and medicine

2018 Volume 98, Page(s) 39–47

Abstract: Brain tumour segmentation in medical images is a very challenging task due to the large variety in tumour shape, position, appearance, scanning modalities and scanning parameters. Most existing segmentation algorithms use information from four different ... ...

Abstract	Brain tumour segmentation in medical images is a very challenging task due to the large variety in tumour shape, position, appearance, scanning modalities and scanning parameters. Most existing segmentation algorithms use information from four different MRI-sequences, but since this is often not available, there is need for a method able to delineate the different tumour tissues based on a minimal amount of data. We present a novel approach using a Random Forests model combining voxelwise texture and abnormality features on a contrast-enhanced T1 and FLAIR MRI. We transform the two scans into 275 feature maps. A random forest model next calculates the probability to belong to 4 tumour classes or 5 normal classes. Afterwards, a dedicated voxel clustering algorithm provides the final tumour segmentation. We trained our method on the BraTS 2013 database and validated it on the larger BraTS 2017 dataset. We achieve median Dice scores of 40.9% (low-grade glioma) and 75.0% (high-grade glioma) to delineate the active tumour, and 68.4%/80.1% for the total abnormal region including edema. Our fully automated brain tumour segmentation algorithm is able to delineate contrast enhancing tissue and oedema with high accuracy based only on post-contrast T1-weighted and FLAIR MRI, whereas for non-enhancing tumour tissue and necrosis only moderate results are obtained. This makes the method especially suitable for high-grade glioma.
MeSH term(s)	Algorithms ; Brain/diagnostic imaging ; Brain Neoplasms/diagnostic imaging ; Databases, Factual ; Glioma/diagnostic imaging ; Humans ; Image Interpretation, Computer-Assisted/methods ; Machine Learning ; Magnetic Resonance Imaging/methods ; Reproducibility of Results
Language	English
Publishing date	2018-05-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	127557-4
ISSN	1879-0534 ; 0010-4825
ISSN (online)	1879-0534
ISSN	0010-4825
DOI	10.1016/j.compbiomed.2018.05.005
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