Search

This study investigates the usefulness of quantitative SUVR thresholds on sub types of typical (type A) and atypical (non-type A) positive (Aβ+) and negative (Aβ-) 18F-florbetapir scans and aims to optimise the thresholds. Clinical 18F-florbetapir scans (n = 100) were categorised by sub type and visual reads were performed independently by three trained readers. Inter-reader agreement and reader-to-reference agreement were measured. Optimal SUVR thresholds were derived by ROC analysis and were compared with thresholds derived from a healthy control group and values from published literature. Sub type division of 18F-florbetapir PET scans improves accuracy and agreement of visual reads for type A: accuracy 90%, 96% and 70% and agreement κ > 0.7, κ ≥ 0.85 and −0.1 < κ < 0.9 for all data, type A and non-type A respectively. Sub type division also improves quantitative classification accuracy of type A: optimum mcSUVR thresholds were found to be 1.32, 1.18 and 1.48 with accuracy 86%, 92% and 76% for all data, type A and non-type A respectively. Aβ+/Aβ- mcSUVR threshold of 1.18 is suitable for classification of type A studies (sensitivity = 97%, specificity = 88%). Region-wise SUVR thresholds may improve classification accuracy in non-type A studies. Amyloid PET scans should be divided by sub type before quantification. We have derived and validated mcSUVR thresholds for Aβ+/Aβ- 18F-florbetapir studies. This work demonstrates that division into sub types improves reader accuracy and agreement and quantification accuracy in scans with typical presentation and highlights the atypical presentations not suited to global SUVR quantification. [ABSTRACT FROM AUTHOR]

The number of people living with dementia is increasing, but as yet there remains no cure or disease-modifying treatment. This review aims to help readers understand the role of 18F-FDG PET/CT imaging in the investigation of cognitive impairment and how the advent of amyloid PET/CT imaging may hold the key to radically changing management of the most common form of dementia - Alzheimer's disease. The indications for 18F-FDG PET/CT and amyloid PET/CT imaging in cognitive impairment are outlined. Additionally, the mechanisms of action, technique, patient preparation and acquisition parameters for both are detailed. We conclude by providing a framework for interpreting 18F-FDG PET/CT and amyloid PET/CT imaging in the more common conditions that lead to cognitive impairment conditions with tips on avoiding pitfalls in interpretation. [ABSTRACT FROM AUTHOR]

Introduction: Overlooking the heterogeneity in Alzheimer's disease (AD) may lead to diagnostic delays and failures. Neuroanatomical normative modeling captures individual brain variation and may inform our understanding of individual differences in AD-related atrophy., Methods: We applied neuroanatomical normative modeling to magnetic resonance imaging from a real-world clinical cohort with confirmed AD ( n  = 86). Regional cortical thickness was compared to a healthy reference cohort ( n  = 33,072) and the number of outlying regions was summed (total outlier count) and mapped at individual- and group-levels., Results: The superior temporal sulcus contained the highest proportion of outliers (60%). Elsewhere, overlap between patient atrophy patterns was low. Mean total outlier count was higher in patients who were non-amnestic, at more advanced disease stages, and without depressive symptoms. Amyloid burden was negatively associated with outlier count., Discussion: Brain atrophy in AD is highly heterogeneous and neuroanatomical normative modeling can be used to explore anatomo-clinical correlations in individual patients., Competing Interests: J.L. is employed by Hermes Medical Solutions and obtains a salary from them; he is Vice President of Research and Development at Hermes Medical Solutions. Z.W. previously participated in the Eli Lilly PET advisory board and was an amyloid‐PET read trainer. R.P. previously sat on an advisory board for Eli Lilly and received support from GE for research imaging from 2014 to 2018. PM gave an educational talk at a meeting organized by GE. None of the authors currently have funding or support from any commercial organization involved in amyloid PET imaging. Author disclosures are available in the supporting information., (© 2024 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Malignant transformation is characterised by aberrant phospholipid metabolism of cancers, associated with the upregulation of choline kinase alpha (CHKα). Due to the metabolic instability of choline radiotracers and the increasing use of late-imaging protocols, we developed a more stable choline radiotracer, [ 18 F]fluoromethyl-[1,2- 2 H 4 ]choline ([ 18 F]D4-FCH). [ 18 F]D4-FCH has improved protection against choline oxidase, the key choline catabolic enzyme, via a 1 H/ 2 D isotope effect, together with fluorine substitution. Due to the promising mechanistic and safety profiles of [ 18 F]D4-FCH in vitro and preclinically, the radiotracer has transitioned to clinical development. [ 18 F]D4-FCH is a safe positron emission tomography (PET) tracer, with a favourable radiation dosimetry profile for clinical imaging. [ 18 F]D4-FCH PET/CT in lung and prostate cancers has shown highly heterogeneous intratumoral distribution and large lesion variability. Treatment with abiraterone or enzalutamide in metastatic castrate-resistant prostate cancer patients elicited mixed responses on PET at 12-16 weeks despite predominantly stable radiological appearances. The sum of the weighted tumour-to-background ratios (TBRs-wsum) was associated with the duration of survival.

Systems vaccinology has been applied to detect signatures of human vaccine induced immunity but its ability, together with high definition in vivo clinical imaging is not established to predict vaccine reactogenicity. Within two European Commission funded high impact programs, BIOVACSAFE and ADITEC, we applied high resolution positron emission tomography/computed tomography (PET/CT) scanning using tissue-specific and non-specific radioligands together with transcriptomic analysis of muscle biopsies in a clinical model systematically and prospectively comparing vaccine-induced immune/inflammatory responses. 109 male participants received a single immunization with licensed preparations of either AS04-adjuvanted hepatitis B virus vaccine (AHBVV); MF59C-adjuvanted (ATIV) or unadjuvanted seasonal trivalent influenza vaccine (STIV); or alum-OMV-meningococcal B protein vaccine (4CMenB), followed by a PET/CT scan (n = 54) or an injection site muscle biopsy (n = 45). Characteristic kinetics was observed with a localized intramuscular focus associated with increased tissue glycolysis at the site of immunization detected by 18 F-fluorodeoxyglucose (FDG) PET/CT, peaking after 1-3 days and strongest and most prolonged after 4CMenB, which correlated with clinical experience. Draining lymph node activation peaked between days 3-5 and was most prominent after ATIV. Well defined uptake of the immune cell-binding radioligand 11 C-PBR28 was observed in muscle lesions and draining lymph nodes. Kinetics of muscle gene expression module upregulation reflected those seen previously in preclinical models with a very early (~6hrs) upregulation of monocyte-, TLR- and cytokine/chemokine-associated modules after AHBVV, in contrast to a response on day 3 after ATIV, which was bracketed by whole blood responses on day 1 as antigen presenting, inflammatory and innate immune cells trafficked to the site of immunization, and on day 5 associated with activated CD4+ T cells. These observations confirm the use of PET/CT, including potentially tissue-, cell-, or cytokine/chemokine-specific radioligands, is a safe and ethical quantitative technique to compare candidate vaccine formulations and could be safely combined with biopsy to guide efficient collection of samples for integrated whole blood and tissue systems vaccinology in small-scale but intensive human clinical models of immunization and to accelerate clinical development and optimisation of vaccine candidates, adjuvants, and formulations., Competing Interests: PD and GG are employees of the GSK group of companies, and report receiving restricted shares of the company. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Win, Weiner 3rd, Listanco, Patel, Sharma, Greenwood, Maertzdorf, Mollenkopf, Pizzoferro, Cole, Bodinham, Kaufmann, Denoel, Del Giudice and Lewis.)

Accurate disease monitoring is essential after transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) because of the potential for profound adverse events and large variations in survival outcome. Posttreatment changes on conventional imaging can confound determination of residual or recurrent disease, magnifying the clinical challenge. On the basis of increased expression of thymidylate synthase ( TYMS ), thymidine kinase 1 ( TK-1 ), and equilibrative nucleoside transporter 1 ( SLC29A1 ) in HCC compared with liver tissue, we conducted a proof-of-concept study evaluating the efficacy of 3'-deoxy-3'- 18 F-fluorothymidine ( 18 F-FLT) PET to assess response to TACE. Because previous PET studies in HCC have been hampered by high background liver signal, we investigated whether a temporal-intensity voxel clustering (kinetic spatial filtering, or KSF) improved lesion detection. Methods: A tissue microarray was built from 36 HCC samples and from matching surrounding cirrhotic tissue and was stained for TK-1 A prospective study was conducted; 18 patients with a diagnosis of HCC by the criteria of the American Association for the Study of Liver Diseases who were eligible for treatment with TACE were enrolled. The patients underwent baseline conventional imaging and dynamic 18 F-FLT PET with KSF followed by TACE. Imaging was repeated 6-8 wk after TACE. The PET parameters were compared with modified enhancement-based RECIST. Results: Cancer Genome Atlas analysis revealed increased RNA expression of TYMS, TK-1, and SLC29A1 in HCC. TK-1 protein expression was significantly higher in HCC ( P < 0.05). The sensitivity of 18 F-FLT PET for baseline HCC detection was 73% (SUV max , 9.7 ± 3.0; tumor to liver ratio, 1.2 ± 0.3). Application of KSF did not improve lesion detection. Lesion response after TACE by modified RECIST was 58% (14 patients with 24 lesions). A 30% reduction in mean 18 F-FLT PET uptake was observed after TACE, correlating with an observed PET response of 60% (15/25). A significant and profound reduction in the radiotracer delivery parameter K 1 after TACE was observed. Conclusion: 18 F-FLT PET can differentiate HCC from surrounding cirrhotic tissue, with PET parameters correlating with TACE response. KSF did not improve visualization of tumor lesions. These findings warrant further investigation., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

The number of people living with dementia is increasing, but as yet there remains no cure or disease-modifying treatment. This review aims to help readers understand the role of 18 F-FDG PET/CT imaging in the investigation of cognitive impairment and how the advent of amyloid PET/CT imaging may hold the key to radically changing management of the most common form of dementia - Alzheimer's disease. The indications for 18 F-FDG PET/CT and amyloid PET/CT imaging in cognitive impairment are outlined. Additionally, the mechanisms of action, technique, patient preparation and acquisition parameters for both are detailed. We conclude by providing a framework for interpreting 18 F-FDG PET/CT and amyloid PET/CT imaging in the more common conditions that lead to cognitive impairment conditions with tips on avoiding pitfalls in interpretation.

The advent of neurochemical brain imaging methods has provided an opportunity to study the neurochemistry of the human brain in normal and abnormal development. The aim of this article is to provide an update on recent major developments in neurochemical imaging in schizophrenia research. In this concise review, we discuss the major findings on three neurotransmitters, namely dopamine, serotonin and glutamate. The most promising radioligand for D(2)/D(3) neuroreceptor imaging is the agonist [(11)C]PHNO, with higher in vivo affinity for D(3) than D(2) receptors, which can be used to measure amphetamine-induced release of dopamine, and therefore a potential model of dopaminergic alterations in schizophrenia. Recent development of selective radiotracers allow imaging of the serotonin transporter (SERT) using positron emission tomography (PET) with selective tracers such as [(11)C]DASB. Additionally, the glutamatergic hypothesis has evolved from theory to phase III clinical trials of newer agents with novel mechanisms. With the development of newer radioligands and the in vivo application of magnetic resonance spectroscopy (MRS) at relatively high magnetic field strengths, there is ample scope for further neuroimaging advances.