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This study investigated whether radiomic features extracted from pretreatment [18F]FDG PET could improve the prediction of both histopathologic tumor response and survival in patients with locally advanced cervical cancer (LACC) treated with neoadjuvant chemoradiotherapy followed by surgery compared with conventional PET parameters and histopathologic features. Methods: The medical records of all consecutive patients with LACC referred between July 2010 and July 2016 were reviewed. [18F]FDG PET/CT was performed before neoadjuvant chemoradiotherapy. Radiomic features were extracted from the primary tumor volumes delineated semiautomatically on the PET images and reduced by factor analysis. A receiver-operating-characteristic analysis was performed, and conventional and radiomic features were dichotomized with Liu's method according to pathologic response (pR) and cancer-specific death. According to the study protocol, only areas under the curve of more than 0.70 were selected for further analysis, including logistic regression analysis for response reduction and Cox regression analysis for survival prediction. Results: A total of 195 patients fulfilled the inclusion criteria. At pathologic evaluation after surgery, 131 patients (67.2%) had no or microscopic (≤3 mm) residual tumor (pR0 or pR1, respectively); 64 patients (32.8%) had macroscopic residual tumor (>3 mm, pR2). With a median follow-up of 76.0 mo (95% CI, 70.7-78.7 mo), 31.3% of patients had recurrence or progression and 20.0% died of the disease. Among conventional PET parameters, SUVmean significantly differed between pathologic responders and nonresponders. Among radiomic features, 1 shape and 3 textural features significantly differed between pathologic responders and nonresponders. Three radiomic features significantly differed between presence and absence of recurrence or progression and between presence and absence of cancer-specific death. Areas under the curve were less than 0.70 for all paramete

01 juni 2023, Item does not contain fulltext, PURPOSE: Positron emission tomography imaging of zirconium-89-labelled monoclonal antibodies ((89)Zr-Immuno-PET) allows for visualisation and quantification of antibody uptake in tumours in vivo. Patlak linearization provides distribution volume (V(T)) and nett influx rate (K(i)) values, representing reversible and irreversible uptake, respectively. Standardised uptake value (SUV) and tumour-to-plasma/tumour-to-blood ratio (TPR/TBR) are often used, but their validity depends on the comparability of plasma kinetics and clearances. This study assesses the validity of SUV, TPR and TBR against Patlak K(i) for quantifying irreversible (89)Zr-Immuno-PET uptake in tumours. METHODS: Ten patients received 37 MBq 10 mg (89)Zr-anti-EGFR with 500 mg/m(2) unlabelled mAbs. Five patients received two doses of 37 MBq (89)Zr-anti-HER3: 8-24 mg for the first administration and 24 mg-30 mg/kg for the second. Seven tumours from four patients showed (89)Zr-anti-EGFR uptake, and 18 tumours from five patients showed (89)Zr-anti-HER3 uptake. SUV(peak,) TPR(peak) and TBR(peak) values were obtained from one to six days p.i. Patlak linearization was applied to tumour time activity curves and plasma samples to obtain K(i). RESULTS: For (89)Zr-anti-EGFR, there was a small variability along the linear regression line between SUV (- 0.51-0.57), TPR (- 0.06‒0.11) and TBR (- 0.13‒0.16) on day 6 versus K(i). Similar doses of (89)Zr-anti-HER3 showed similar variability for SUV (- 1.3‒1.0), TPR (- 1.1‒0.53) and TBR (- 1.5‒0.72) on day 5 versus K(i). However, for the second administration of (89)Zr-anti-HER3 with a large variability in administered mass doses, SUV showed a larger variability (- 1.4‒2.3) along the regression line with K(i), which improved when using TPR (- 0.38-0.32) or TBR (- 0.56‒0.46). CONCLUSION: SUV, TPR and TBR at late time points were valid for quantifying irreversible lesional (89)Zr-Immuno-PET uptake when constant mass doses were administered. However, for variable mass doses

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Item does not contain fulltext, Upregulation of prostate-specific membrane antigen (PSMA) in neovasculature has been described in glioblastoma multiforme (GBM), whereas vasculature in nonaffected brain shows hardly any expression of PSMA. It is unclear whether PSMA-targeting tracer uptake on PET is based on PSMA-specific binding to neovasculature or aspecific uptake in tumor. Here, we quantified uptake of various PSMA-targeting tracers in GBM and correlated this with PSMA expression in tumor biopsy samples from the same patients. Methods: Fourteen patients diagnosed with de novo (n = 8) or recurrent (n = 6) GBM underwent a preoperative PET scan after injection of 1.5 MBq/kg [(68)Ga]Ga-PSMA-11 (n = 7), 200 MBq of [(18)F]DCFpyl (n = 3), or 200 MBq of [(18)F]PSMA-1007 (n = 4). Uptake in tumor and tumor-to-background ratios, with contralateral nonaffected brain as background, were determined. In a subset of patients, PSMA expression levels from different regions in the tumor tissue samples (n = 40), determined using immunohistochemistry (n = 35) or RNA sequencing (n = 13), were correlated with tracer uptake on PET. Results: Moderate to high (SUV(max), 1.3-20.0) heterogeneous uptake was found in all tumors irrespective of the tracer type used. Uptake in nonaffected brain was low, resulting in high tumor-to-background ratios (6.1-359.0) calculated by dividing SUV(max) of tumor by SUV(max) of background. Immunohistochemistry showed variable PSMA expression on endothelial cells of tumor microvasculature, as well as on dispersed individual cells (of unknown origin), and granular staining of the neuropil. No correlation was found between in vivo uptake and PSMA expression levels (for immunohistochemistry, r = -0.173, P = 0.320; for RNA, r = -0.033, P = 0.915). Conclusion: Our results indicate the potential use of various PSMA-targeting tracers in GBM. However, we found no correlation between PSMA expression levels on immunohistochemistry and uptake intensity on PET. Whether this may be explained by methodol

Item does not contain fulltext, PURPOSE: MYC gene rearrangements in diffuse large B-cell lymphoma (DLBCL) patients are associated with poor prognosis. Our aim was to compare patterns of 2[(18)F]fluoro-2-deoxy-D-glucose positron emission tomography computed tomography (PET/CT) response in MYC + and MYC- DLBCL patients. METHODS: Interim PET/CT (I-PET) and end of treatment PET/CT (EoT-PET) scans of 81 MYC + and 129 MYC- DLBCL patients from 2 HOVON trials were reviewed using the Deauville 5-point scale (DS). DS1-3 was regarded as negative and DS4-5 as positive. Standardized uptake values (SUV) and metabolic tumor volume (MTV) were quantified at baseline, I-PET, and EoT-PET. Negative (NPV) and positive predictive values (PPV) were calculated using 2-year overall survival. RESULTS: MYC + DLBCL patients had significantly more positive EoT-PET scans than MYC- patients (32.5 vs 15.7%, p = 0.004). I-PET positivity rates were comparable (28.8 vs 23.8%). In MYC + patients 23.2% of the I-PET negative patients converted to positive at EoT-PET, vs only 2% for the MYC- patients (p = 0.002). Nine (34.6%) MYC + DLBCL showed initially uninvolved localizations at EoT-PET, compared to one (5.3%) MYC- patient. A total of 80.8% of EoT-PET positive MYC + patients showed both increased lesional SUV and MTV compared to I-PET. In MYC- patients, 31.6% showed increased SUV and 42.1% showed increased MTV. NPV of I-PET and EoT-PET was high for both MYC subgroups (81.8-94.1%). PPV was highest at EoT-PET for MYC + patients (61.5%). CONCLUSION: MYC + DLBCL patients demonstrate aberrant PET response patterns compared to MYC- patients with more frequent progression during treatment after I-PET negative assessment and new lesions at sites that were not initially involved. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: HOVON-84: EudraCT: 2006-005,174-42, retrospectively registered 01-08-2008. HOVON-130: EudraCT: 2014-002,654-39, registered 26-01-2015.

Background: Arterial spin-labeling (ASL) is a viable non-invasive alternative to dynamic susceptibility contrast (DSC) for measuring cerebral blood flow (CBF). While quantitative accuracy of ASL and DSC was compared in healthy volunteers and patients, a comparison to a reference standard in patients diagnosed with glioma is still missing. Purpose: To probe the quantitative agreement between perfusion measurements based on ASL and DSC in comparison to the gold standard of PET in patients with glioma. Materials and Methods: This secondary analysis included pre-surgical ASL and DSC perfusion measurements in participants diagnosed with grade 2-4 gliomas drawn from the prospective FRONTIER study (Dutch National Trial Register - NTR5354) and compared the two techniques with the gold-standard perfusion measurement 15O-H2O-PET. The quantitative comparison was performed both in normal-appearing tissue as well as in the tumor region. The mean, maximum, and voxel-wise perfusion values were with and without normalization to normal-appearing tissue. And finally, a qualitative analysis was performed on individual cases to help interpret the quantitative results. Results: Eight patients (age 40.5 ± 17.0 years, 3 women) were analyzed. ASL showed better voxel-wise agreement with PET in the normal-appearing tissue than DSC (mean relative error of 26.8% vs. 33.8%). Within the tumor, cerebral blood flow (CBF) normalized contralateral gray matter showed similar tumor maximum values in both techniques - mean relative error of 23.2% for ASL and 22.0% for DSC. However, the mean relative error on a voxel-wise basis was better for ASL (27.2%) than for DSC (35.0%). Qualitatively, ASL tended to overestimate CBF in macrovessels, and DSC tended to overestimate CBF in non-enhancing tumors with small vessel diameters. Conclusion: While neither ASL nor DSC can readily replace 15O-H2O-PET in tumor quantitative perfusion measurement, ASL CBF presents a viable non-invasive semi-quantitative alternativ

Various factors have been identified that influence quantitative accuracy and image interpretation in positron emission tomography (PET). Through the continuous introduction of new PET technology—both imaging hardware and reconstruction software—into clinical care, we now find ourselves in a transition period in which traditional and new technologies coexist. The effects on the clinical value of PET imaging and its interpretation in routine clinical practice require careful reevaluation. In this review, we provide a comprehensive summary of important factors influencing quantification and interpretation with a focus on recent developments in PET technology. Finally, we discuss the relationship between quantitative accuracy and subjective image interpretation.

Recent studies in neurodegenerative conditions have increasingly highlighted that the same neuropathology can trigger different clinical phenotypes or, vice-versa, that similar phenotypes can be triggered by different neuropathologies. This evidence has called for the adoption of a pathology spectrum-based approach to study neurodegenerative proteinopathies. These conditions share brain deposition of abnormal protein aggregates, leading to aberrant biochemical, metabolic, functional, and structural changes. Positron emission tomography (PET) is a well-recognized and unique tool for the in vivo assessment of brain neuropathology, and novel PET techniques are emerging for the study of specific protein species. Today, key applications of PET range from early research and clinical diagnostic tools to their use in clinical trials for both participants screening and outcome evaluation. This position article critically reviews the role of distinct PET molecular tracers for different neurodegenerative proteinopathies, highlighting their strengths, weaknesses, and opportunities, with special emphasis on methodological challenges and future applications.

Introduction: A rapid transition from a clinical-based classification to a pathology-based classification of neurodegenerative conditions, largely promoted by the increasing availability of imaging biomarkers, is emerging. The Framework for Innovative Multi-tracer molecular Brain Imaging, funded by the EU Joint Program - Neurodegenerative Disease Research 2016 “Working Groups for Harmonisation and Alignment in Brain Imaging Methods for Neurodegeneration,” aimed at providing a roadmap for the applications of established and new molecular imaging techniques in dementia. Methods: We consider current and future implications of adopting a pathology-based framework for the use and development of positron emission tomography techniques. Results: This approach will enhance efforts to understand the multifactorial etiology of Alzheimer's disease and other dementias. Discussion: The availability of pathology biomarkers will soon transform clinical and research practice. Crucially, a comprehensive understanding of strengths and caveats of these techniques will promote an informed use to take full advantage of these tools.