Purpose
CXCR4 (over)expression is found in multiple human cancer types, while expression is low or absent in healthy tissue. In glioblastoma it is associated with a poor prognosis and more extensive ...infiltrative phenotype. CXCR4 can be targeted by the diagnostic PET agent
68
GaGa-Pentixafor and its therapeutic counterpart
177
LuLu-Pentixather. We aimed to investigate the expression of CXCR4 in glioblastoma tissue to further examine the potential of these PET agents.
Methods
CXCR4 mRNA expression was examined using the R2 genomics platform. Glioblastoma tissue cores were stained for CXCR4. CXCR4 staining in tumor cells was scored. Stained tissue components (cytoplasm and/or nuclei of the tumor cells and blood vessels) were documented. Clinical characteristics and information on IDH and
MGMT
promoter methylation status were collected. Seven pilot patients with recurrent glioblastoma underwent
68
GaGa-Pentixafor PET; residual resected tissue was stained for CXCR4.
Results
Two large mRNA datasets (
N
= 284;
N
= 540) were assesed. Of the 191 glioblastomas, 426 cores were analyzed using immunohistochemistry. Seventy-eight cores (23 tumors) were CXCR4 negative, while 18 cores (5 tumors) had both strong and extensive staining. The remaining 330 cores (163 tumors) showed a large inter- and intra-tumor variation for CXCR4 expression; also seen in the resected tissue of the seven pilot patients—not directly translatable to
68
GaGa-Pentixafor PET results. Both mRNA and immunohistochemical analysis showed CXCR4 negative normal brain tissue and no significant correlation between CXCR4 expression and IDH or
MGMT
status or survival.
Conclusion
Using immunohistochemistry, high CXCR4 expression was found in a subset of glioblastomas as well as a large inter- and intra-tumor variation. Caution should be exercised in directly translating ex vivo CXCR4 expression to PET agent uptake. However, when high CXCR4 expression can be identified with
68
GaGa-Pentixafor, these patients might be good candidates for targeted radionuclide therapy with
177
LuLu-Pentixather in the future.
A major pathological hallmark of Alzheimer's disease is accumulation of amyloid-β in senile plaques in the brain. Evidence is accumulating that decreased clearance of amyloid-β from the brain may ...lead to these elevated amyloid-β levels. One of the clearance pathways of amyloid-β is transport across the blood-brain barrier via efflux transporters. P-glycoprotein, an efflux pump highly expressed at the endothelial cells of the blood-brain barrier, has been shown to transport amyloid-β. P-glycoprotein function can be assessed in vivo using (R)-11Cverapamil and positron emission tomography. The aim of this study was to assess blood-brain barrier P-glycoprotein function in patients with Alzheimer's disease compared with age-matched healthy controls using (R)-11Cverapamil and positron emission tomography. In 13 patients with Alzheimer's disease (age 65 ± 7 years, Mini-Mental State Examination 23 ± 3), global (R)-11Cverapamil binding potential values were increased significantly (P = 0.001) compared with 14 healthy controls (aged 62 ± 4 years, Mini-Mental State Examination 30 ± 1). Global (R)-11Cverapamil binding potential values were 2.18 ± 0.25 for patients with Alzheimer's disease and 1.77 ± 0.41 for healthy controls. In patients with Alzheimer's disease, higher (R)-11Cverapamil binding potential values were found for frontal, parietal, temporal and occipital cortices, and posterior and anterior cingulate. No significant differences between groups were found for medial temporal lobe and cerebellum. These data show altered kinetics of (R)-11Cverapamil in Alzheimer's disease, similar to alterations seen in studies where P-glycoprotein is blocked by a pharmacological agent. As such, these data indicate that P-glycoprotein function is decreased in patients with Alzheimer's disease. This is the first direct evidence that the P-glycoprotein transporter at the blood-brain barrier is compromised in sporadic Alzheimer's disease and suggests that decreased P-glycoprotein function may be involved in the pathogenesis of Alzheimer's disease.
Objectives
To assess the concordance of whole-body MRI (WB-MRI) and an FDG-PET/CT-based reference standard for the initial staging in children with Hodgkin lymphoma (HL)
Methods
Children with newly ...diagnosed HL were included in this prospective, multicentre, international study and underwent WB-MRI and FDG-PET/CT at staging. Two radiologists and a nuclear medicine physician independently evaluated all images. Discrepancies between WB-MRI and FDG-PET/CT were assessed by an expert panel. All FDG-PET/CT errors were corrected to derive the FDG-PET/CT-based reference standard. The expert panel corrected all reader errors in the WB-MRI DWI dataset to form the intrinsic MRI data. Inter-observer agreement for WB-MRI DWI was calculated using overall agreement, specific agreements and kappa statistics. Concordance for correct classification of all disease sites and disease stage between WB-MRI (without DWI, with DWI and intrinsic WB-MRI DWI) and the reference standard was calculated as primary outcome. Secondary outcomes included positive predictive value, negative predictive value and kappa statistics. Clustering within patients was accounted for using a mixed-effect logistic regression model with random intercepts and a multilevel kappa analysis.
Results
Sixty-eight children were included. Inter-observer agreement between WB-MRI DWI readers was good for disease stage (
κ
= 0.74). WB-MRI DWI agreed with the FDG-PET/CT-based reference standard for determining disease stage in 96% of the patients versus 88% for WB-MRI without DWI. Agreement between WB-MRI DWI and the reference standard was excellent for both nodal (98%) and extra-nodal (100%) staging.
Conclusions
WB-MRI DWI showed excellent agreement with the FDG-PET/CT-based reference standard. The addition of DWI to the WB-MRI protocol improved the staging agreement.
Key Points
• This study showed excellent agreement between WB-MRI DWI and an FDG-PET/CT-based reference standard for staging paediatric HL.
• Diffusion-weighted imaging is a useful addition to WB-MRI in staging paediatric HL.
• Inter-observer agreement for WB-MRI DWI was good for both nodal and extra-nodal staging and determining disease stage.
Appropriate imaging is essential in the treatment of children and adolescents with rhabdomyosarcoma. For adequate stratification and optimal individualised local treatment utilising surgery and ...radiotherapy, high-quality imaging is crucial. The paediatric radiologist, therefore, is an essential member of the multi-disciplinary team providing clinical care and research. This manuscript presents the European rhabdomyosarcoma imaging guideline, based on the recently developed guideline of the European Paediatric Soft Tissue Sarcoma Study Group (EpSSG) Imaging Committee. This guideline was developed in collaboration between the EpSSG Imaging Committee, the Cooperative Weichteilsarkom Studiengruppe (CWS) Imaging Group, and the Oncology Task Force of the European Society of Paediatric Radiology (ESPR). MRI is recommended, at diagnosis and follow-up, for the evaluation of the primary tumour and its relationship to surrounding tissues, including assessment of neurovascular structures and loco-regional lymphadenopathy. Chest CT along with F-182-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET)/CT or PET/MRI are recommended for the detection and evaluation of loco-regional and distant metastatic disease. Guidance on the estimation of treatment response, optimal long-term follow-up, technical imaging settings and standardised reporting are described. This European imaging guideline outlines the recommendations for imaging in children and adolescents with rhabdomyosarcoma, with the aim to harmonise imaging and to advance patient care.
Objectives
To compare WB-MRI with an
18
FFDG-PET/CT-based reference for early response assessment and restaging in children with Hodgkin’s lymphoma (HL).
Methods
Fifty-one children (ages 10–17) with ...HL were included in this prospective, multicentre study. All participants underwent WB-MRI and
18
FFDG-PET/CT at early response assessment. Thirteen of the 51 patients also underwent both WB-MRI and
18
FFDG-PET/CT at restaging. Two radiologists independently evaluated all WB-MR images in two separate readings: without and with DWI. The
18
FFDG-PET/CT examinations were evaluated by a nuclear medicine physician. An expert panel assessed all discrepancies between WB-MRI and
18
FFDG-PET/CT to derive the
18
FFDG-PET/CT-based reference standard. Inter-observer agreement for WB-MRI was calculated using kappa statistics. Concordance, PPV, NPV, sensitivity and specificity for a correct assessment of the response between WB-MRI and the reference standard were calculated for both nodal and extra-nodal disease presence and total response evaluation.
Results
Inter-observer agreement of WB-MRI including DWI between both readers was moderate (
κ
0.46–0.60). For early response assessment, WB-MRI DWI agreed with the reference standard in 33/51 patients (65%, 95% CI 51–77%) versus 15/51 (29%, 95% CI 19–43%) for WB-MRI without DWI. For restaging, WB-MRI including DWI agreed with the reference standard in 9/13 patients (69%, 95% CI 42–87%) versus 5/13 patients (38%, 95% CI 18–64%) for WB-MRI without DWI.
Conclusions
The addition of DWI to the WB-MRI protocol in early response assessment and restaging of paediatric HL improved agreement with the
18
FFDG-PET/CT-based reference standard. However, WB-MRI remained discordant in 30% of the patients compared to standard imaging for assessing residual disease presence.
Key Points
• Inter-observer agreement of WB-MRI including DWI between both readers was moderate for (early) response assessment of paediatric Hodgkin’s lymphoma.
• The addition of DWI to the WB-MRI protocol in early response assessment and restaging of paediatric Hodgkin’s lymphoma improved agreement with the 18FFDG-PET/CT-based reference standard.
• WB-MRI including DWI agreed with the reference standard in respectively 65% and 69% of the patients for early response assessment and restaging.
Objective
Cerebral perfusion analysis based on arterial spin labeling (ASL) MRI has been proposed as an alternative to FDG-PET in patients with neurodegenerative disease. Z-maps show normal ...distribution values relating an image to a database of controls. They are routinely used for FDG-PET to demonstrate disease-specific patterns of hypometabolism at the individual level. This study aimed to compare the performance of Z-maps based on ASL to FDG-PET.
Methods
Data were combined from two separate sites, each cohort consisting of patients with Alzheimer’s disease (
n
= 18 + 7), frontotemporal dementia (
n
= 12 + 8) and controls (
n
= 9 + 29). Subjects underwent pseudocontinuous ASL and FDG-PET. Z-maps were created for each subject and modality. Four experienced physicians visually assessed the 166 Z-maps in random order, blinded to modality and diagnosis.
Results
Discrimination of patients versus controls using ASL-based Z-maps yielded high specificity (84%) and positive predictive value (80%), but significantly lower sensitivity compared to FDG-PET-based Z-maps (53% vs. 96%,
p
< 0.001). Among true-positive cases, correct diagnoses were made in 76% (ASL) and 84% (FDG-PET) (
p
= 0.168).
Conclusion
ASL-based Z-maps can be used for visual assessment of neurodegenerative dementia with high specificity and positive predictive value, but with inferior sensitivity compared to FDG-PET.
Key points
•
ASL-based Z-maps yielded high specificity and positive predictive value in neurodegenerative dementia.
•
ASL-based Z-maps had significantly lower sensitivity compared to FDG-PET-based Z-maps.
•
FDG-PET might be reserved for ASL-negative cases where clinical suspicion persists.
•
Findings were similar at two study sites.
To improve identification of peritoneal and distant metastases in locally advanced gastric cancer using
FFDG-PET radiomics.
FFDG-PET scans of 206 patients acquired in 16 different Dutch hospitals ...in the prospective multicentre PLASTIC-study were analysed. Tumours were delineated and 105 radiomic features were extracted. Three classification models were developed to identify peritoneal and distant metastases (incidence: 21%): a model with clinical variables, a model with radiomic features, and a clinicoradiomic model, combining clinical variables and radiomic features. A least absolute shrinkage and selection operator (LASSO) regression classifier was trained and evaluated in a 100-times repeated random split, stratified for the presence of peritoneal and distant metastases. To exclude features with high mutual correlations, redundancy filtering of the Pearson correlation matrix was performed (r = 0.9). Model performances were expressed by the area under the receiver operating characteristic curve (AUC). In addition, subgroup analyses based on Lauren classification were performed.
None of the models could identify metastases with low AUCs of 0.59, 0.51, and 0.56, for the clinical, radiomic, and clinicoradiomic model, respectively. Subgroup analysis of intestinal and mixed-type tumours resulted in low AUCs of 0.67 and 0.60 for the clinical and radiomic models, and a moderate AUC of 0.71 in the clinicoradiomic model. Subgroup analysis of diffuse-type tumours did not improve the classification performance.
Overall,
FFDG-PET-based radiomics did not contribute to the preoperative identification of peritoneal and distant metastases in patients with locally advanced gastric carcinoma. In intestinal and mixed-type tumours, the classification performance of the clinical model slightly improved with the addition of radiomic features, but this slight improvement does not outweigh the laborious radiomic analysis.
Purpose
Moderate-to-high correlations have been reported between the
11
CPiB PET-derived relative tracer delivery rate
R
1
and relative CBF as measured using
15
OH
2
O PET, supporting its use as a ...proxy of relative CBF. As longitudinal PET studies become more common for measuring treatment efficacy or disease progression, it is important to know the intrinsic variability of
R
1
. The purpose of the present study was to determine this through a retrospective data analysis.
Procedures
Test-retest data belonging to twelve participants, who underwent two 90 min
11
CPiB PET scans, were retrospectively included. The voxel-based implementation of the two-step simplified reference tissue model with cerebellar grey matter as reference tissue was used to compute
R
1
images. Next, test-retest variability was calculated, and test and retest
R
1
measures were compared using linear mixed effect models and a Bland-Altman analysis.
Results
Test-retest variability was low across regions (max. 5.8 %), and test and retest measures showed high, significant correlations (
R
2
=0.92, slope=0.98) and a negligible bias (0.69±3.07 %).
Conclusions
In conclusion, the high precision of
11
CPiB
R
1
suggests suitable applicability for cross-sectional and longitudinal studies.
Systems Radiology and Personalized Medicine Foppen, Wouter; Tolboom, Nelleke; de Jong, Pim A.
Journal of personalized medicine,
08/2021, Volume:
11, Issue:
8
Journal Article
Peer reviewed
Open access
Medicine has evolved into a high level of specialization using the very detailed imaging of organs ...
The post-treatment imaging surveillance of gliomas is challenged by distinguishing tumor progression (TP) from treatment-related abnormalities (TRA). Sophisticated imaging techniques, such as ...perfusion-weighted magnetic resonance imaging (MRI PWI) and positron-emission tomography (PET) with a variety of radiotracers, have been suggested as being more reliable than standard imaging for distinguishing TP from TRA. However, it remains unclear if any technique holds diagnostic superiority. This meta-analysis provides a head-to-head comparison of the diagnostic accuracy of the aforementioned imaging techniques. Systematic literature searches on the use of PWI and PET imaging techniques were carried out in PubMed, Embase, the Cochrane Library, ClinicalTrials.gov and the reference lists of relevant papers. After the extraction of data on imaging technique specifications and diagnostic accuracy, a meta-analysis was carried out. The quality of the included papers was assessed using the QUADAS-2 checklist. Nineteen articles, totaling 697 treated patients with glioma (431 males; mean age ± standard deviation 50.5 ± 5.1 years) were included. The investigated PWI techniques included dynamic susceptibility contrast (DSC), dynamic contrast enhancement (DCE) and arterial spin labeling (ASL). The PET-tracers studied concerned S-methyl-
Cmethionine, 2-deoxy-2-
Ffluoro-D-glucose (
FFDG), O-(2-
Ffluoroethyl)-L-tyrosine (
FFET) and 6-
F-fluoro-3,4-dihydroxy-L-phenylalanine (
FFDOPA). The meta-analysis of all data showed no diagnostic superior imaging technique. The included literature showed a low risk of bias. As no technique was found to be diagnostically superior, the local level of expertise is hypothesized to be the most important factor for diagnostically accurate results in post-treatment glioma patients regarding the distinction of TRA from TP.
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