Purpose To assess the clinical safety, pharmacokinetics, and tumor imaging characteristics of fluorine 18-(2S,4R)-4-fluoroglutamine (FGln), a glutamine analog radiologic imaging agent. Materials and Methods This study was approved by the institutional review board and conducted under a U.S. Food and Drug Administration-approved Investigational New Drug application in accordance with the Helsinki Declaration and the Health Insurance Portability and Accountability Act. All patients provided written informed consent. Between January 2013 and October 2016, 25 adult patients with cancer received an intravenous bolus of FGln tracer (mean, 244 MBq ± 118, <100 μg) followed by positron emission tomography (PET) and blood radioassays. Patient data were summarized with descriptive statistics. FGln biodistribution and plasma amino acid levels in nonfasting patients (n = 13) were compared with those from patients who fasted at least 8 hours before injection (n = 12) by using nonparametric one-way analysis of variance with Bonferroni correction. Tumor FGln avidity versus fluorodeoxyglucose (FDG) avidity in patients with paired PET scans (n = 15) was evaluated with the Fisher exact test. P < .05 was considered indicative of a statistically significant difference. Results FGln PET depicted tumors of different cancer types (breast, pancreas, renal, neuroendocrine, lung, colon, lymphoma, bile duct, or glioma) in 17 of the 25 patients, predominantly clinically aggressive tumors with genetic mutations implicated in abnormal glutamine metabolism. Acute fasting had no significant effect on FGln biodistribution and plasma amino acid levels. FGln-avid tumors were uniformly FDG-avid but not vice versa (P = .07). Patients experienced no adverse effects. Conclusion Preliminary human FGln PET trial results provide clinical validation of abnormal glutamine metabolism as a potential tumor biomarker for targeted radiotracer imaging in several different cancer types. RSNA, 2018 Online supplemental material is available for this article. Clinical trial registration no. NCT01697930.
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http://dx.doi.org/10.1148/radiol.2017162610 | DOI Listing |
Alzheimers Dement
December 2024
McGill University, Montreal, QC, Canada.
Background: Despite amyloid-β (Aβ) plaques and tau neurofibrillary tangles being recognized as major Alzheimer's Disease (AD) hallmarks, their synergistic contribution to neuronal activity remains unclear. We developed a neuroimaging-based personalized brain activity model to assess the in-vivo functional impact of AD pathophysiology. In previous reports, model-inferred neuronal excitability predicted disease progression (i.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA.
Background: MODEL-AD (Model Organism Development and Evaluation for Late-onset AD) is developing, characterizing, and distributing novel mouse models expressing humanized, clinically relevant genetic risk factors. Models expressing human-relevant risk genetic risk factors are expected to better phenocopy LOAD than widely used transgenic models.
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Alzheimers Dement
December 2024
Department of Clinical Neurosciences and Cambridge University Hospitals NHS Trust, University of Cambridge, Cambridge, United Kingdom.
Background: Frontotemporal dementia (FTD) and Progressive Supranuclear Palsy (PSP) have distinct molecular pathologies, with Tau and TDP43 aggregation, and distinct patterns of regional brain atrophy. However, they share the synaptotoxicity of protein aggregation, and neurotransmitter loss (including GABA), which contribute to clinical and neurophysiological similarities. Defining the relationships between synaptic loss, network physiology and cognition builds bridges between preclinical and clinical studies, and facilitates early phase trials.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of Milano - Bicocca, Monza, Monza, Italy, iCAB International Network, University of Milano - Bicocca, Monza, Italy.
ARIA-E/H (amyloid-related imaging abnormalities-Edema/Hemorrhage) is an umbrella term that defines the radiographic appearance of MRI images abnormality during treatments with Aβ-lowering monoclonal antibodies (mAbs) for Alzheimer's disease immunotherapy. Today, it is well-recognized that ARIA-E events can also occur spontaneously in patients with cerebral amyloid angiopathy-related inflammation (CAA-ri), a rare autoimmune encephalopathy associated with raised cerebrospinal fluid (CSF) concentrations of spontaneous auto-antibodies against Aβ (aAbs). In this framework, the last years of research and experience of the iCAB international Network generated an increased consensus that therapy-induced ARIA is the iatrogenic manifestation of CAA-ri.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of California, Irvine, Irvine, CA, USA.
Background: Recent studies have suggested a transient glucose hypermetabolism in early phases of Alzheimer's Disease (AD), which is followed by a characteristic glucose hypometabolism in dementia stages. This phenomenon desveres further investigation and it is suggested to be associated to glial/inflammatory or compensatory neuronal responses. Here, we aimed to longitudinally investigate brain glucose metabolism in an AD animal model and explore associated cellular and inflammatory changes.
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