l-2-Hydroxyglutarate remodeling of the epigenome and epitranscriptome creates a metabolic vulnerability in kidney cancer models.

Tumor cells are known to undergo considerable metabolic reprogramming to meet their unique demands and drive tumor growth. At the same time, this reprogramming may come at a cost with resultant metabolic vulnerabilities. The small molecule l-2-hydroxyglutarate (l-2HG) is elevated in the most common histology of renal cancer.

Imaging With PET/CT of Diffuse CD8 T-Cell Infiltration of Skeletal Muscle in Patients With Inclusion Body Myositis.

Background And Objectives: Inclusion body myositis (IBM) is a progressive autoimmune skeletal muscle disease in which cytotoxic CD8 T cells infiltrate muscle and destroy myofibers. IBM has required a muscle biopsy for diagnosis. Here, we administered to patients with IBM a novel investigational PET tracer Zr-Df-crefmirlimab for in vivo imaging of whole body skeletal muscle CD8 T cells.

Evidence of neuroinflammation in fibromyalgia syndrome: a [ 18 F]DPA-714 positron emission tomography study.

This observational study aimed to determine whether individuals with fibromyalgia (FM) exhibit higher levels of neuroinflammation than healthy controls (HCs), as measured with positron emission tomography using [ 18 F]DPA-714, a second-generation radioligand for the translocator protein (TSPO). Fifteen women with FM and 10 HCs underwent neuroimaging. Distribution volume (V T ) was calculated for in 28 regions of interest (ROIs) using Logan graphical analysis and compared between groups using multiple linear regressions.

Prediction of MCI-to-AD progression with atrophy-weighted standard uptake value ratios of F-Florbetapir PET.

Unlabelled: Accurate prediction of MCI-to-AD progression is an important yet challenging task. We introduce a new quantitative parameter: the atrophy-weighted standard uptake value ratio (awSUVR), defined as the PET SUVR divided by the hippocampal volume measured with MR, and evaluate whether it may provide better prediction of the MCI-to-AD progression.

Materials And Methods: We used ADNI data to evaluate the prediction performances of the awSUVR against SUVR.

Brain and Systemic Inflammation in De Novo Parkinson's Disease.

Objective: To assess the presence of brain and systemic inflammation in subjects newly diagnosed with Parkinson's disease (PD).

Background: Evidence for a pathophysiologic role of inflammation in PD is growing. However, several key gaps remain as to the role of inflammation in PD, including the extent of immune activation at early stages, potential effects of PD treatments on inflammation and whether pro-inflammatory signals are associated with clinical features and/or predict more rapid progression.

Low-Dose Augmentation With Buprenorphine for Treatment-Resistant Depression: A Multisite Randomized Controlled Trial With Multimodal Assessment of Target Engagement.

Background: The experimental therapeutics approach that combines a placebo-controlled clinical trial with translational neuroscience methods can provide a better understanding of both the clinical and physiological effects of pharmacotherapy. We aimed to test the efficacy and tolerability of low-dose augmentation with buprenorphine (BPN) for treatment-resistant depression, combined with multimodal assessment of target engagement.

Methods: In this multisite randomized clinical trial, 85 participants ≥50 years of age with a major depressive episode that had not responded to venlafaxine extended release were randomized to augmentation with BPN or placebo for 8 weeks.

Investigating Tau and Amyloid Tracer Skull Binding in Studies of Alzheimer Disease.

Off-target binding of [F]flortaucipir (FTP) can complicate quantitative PET analyses. An underdiscussed off-target region is the skull. Here, we characterize how often FTP skull binding occurs, its influence on estimates of Alzheimer disease pathology, its potential drivers, and whether skull uptake is a stable feature across time and tracers.

Image Quantification for TSPO PET with a Novel Image-Derived Input Function Method.

There is a growing interest in using 18F-DPA-714 PET to study neuroinflammation and microglial activation through imaging the 18-kDa translocator protein (TSPO). Although quantification of 18F-DPA-714 binding can be achieved through kinetic modeling analysis with an arterial input function (AIF) measured with blood sampling procedures, the invasiveness of such procedures has been an obstacle for wide application. To address these challenges, we developed an image-derived input function (IDIF) that noninvasively estimates the arterial input function from the images acquired for 18F-DPA-714 quantification.

PET/MRI in Pediatric Neuroimaging: Primer for Clinical Practice.

Modern pediatric imaging seeks to provide not only exceptional anatomic detail but also physiologic and metabolic information of the pathology in question with as little radiation penalty as possible. Hybrid PET/MR imaging combines exquisite soft-tissue information obtained by MR imaging with functional information provided by PET, including metabolic markers, receptor binding, perfusion, and neurotransmitter release data. In pediatric neuro-oncology, PET/MR imaging is, in many ways, ideal for follow-up compared with PET/CT, given the superiority of MR imaging in neuroimaging compared with CT and the lower radiation dose, which is relevant in serial imaging and long-term follow-up of pediatric patients.

Applications of PET/MRI in Abdominopelvic Oncology.

With PET/MRI, the strengths of PET and MRI are combined to allow simultaneous image acquisition and near-perfect image coregistration. MRI is increasingly being used for staging and restaging of abdominopelvic oncologic lesions, including prostate, hepatobiliary, pancreatic, neuroendocrine, cervical, and rectal cancers. Fluorine 18-fluorodeoxyglucose PET/CT has long been considered a cornerstone of oncologic imaging, and the development of multiple targeted radiotracers has led to increased research on and use of these agents in clinical practice.

Clinical Applications of PET/MR Imaging.

PET/MR imaging is in routine clinical use and is at least as effective as PET/CT for oncologic and neurologic studies with advantages with certain PET radiopharmaceuticals and applications. In addition, whole body PET/MR imaging substantially reduces radiation dosages compared with PET/CT which is particularly relevant to pediatric and young adult population. For cancer imaging, assessment of hepatic, pelvic, and soft-tissue malignancies may benefit from PET/MR imaging.

A Path to Qualification of PET/MRI Scanners for Multicenter Brain Imaging Studies: Evaluation of MRI-Based Attenuation Correction Methods Using a Patient Phantom.

PET/MRI scanners cannot be qualified in the manner adopted for hybrid PET/CT devices. The main hurdle with qualification in PET/MRI is that attenuation correction (AC) cannot be adequately measured in conventional PET phantoms because of the difficulty in converting the MR images of the physical structures (e.g.

Dynamic Amyloid PET: Relationships to F-Flortaucipir Tau PET Measures.

Measuring amyloid and predicting tau status using a single amyloid PET study would be valuable for assessing brain AD pathophysiology. We hypothesized that early-frame amyloid PET (efAP) correlates with the presence of tau pathology because the initial regional brain concentrations of radioactivity are determined primarily by blood flow, which is expected to be decreased in the setting of tau pathology. The study included 120 participants (63 amyloid-positive and 57 amyloid-negative) with dynamic F-florbetapir PET and static F-flortaucipir PET scans obtained within 6 mo of each other.

Racial Differences in Alzheimer's Disease Specialist Encounters Are Associated with Usage of Molecular Imaging and Dementia Medications: An Enterprise-Wide Analysis Using i2b2.

Background: African Americans are at increased risk for Alzheimer's disease (AD) but barriers to optimal clinical care are unclear.

Objective: To comprehensively evaluate potential racial differences in the diagnosis and treatment of AD in an academic medical center.

Methods: We used the clinical informatics tool, i2b2, to analyze all patient encounters for AD or mild cognitive impairment (MCI) in the University of Alabama at Birmingham Health System over a three-year period, examining neuroimaging rates and dementia-related medication use by race and clinic site using ratio tests on contingency tables of stratified patient counts.

Production of [ Zr]Oxinate and cell radiolabeling for human use.

[ Zr]Oxinate is a Positron Emission Tomography (PET) tracer for cell radiolabeling that can enable imaging techniques to help better understand cell trafficking in various diseases. Although several groups have synthetized this compound for use in preclinical studies, there is no available data regarding the production of [ Zr]Oxinate for human use. In this report, we describe the detailed production of [ Zr]Oxinate under USP <823> and autologous leukocyte radiolabeling under USP <797>.

Dynamic F-FDOPA-PET/MRI for the preoperative evaluation of gliomas: correlation with stereotactic histopathology.

Background: MRI alone has limited accuracy for delineating tumor margins and poorly predicts the aggressiveness of gliomas, especially when tumors do not enhance. This study evaluated simultaneous 3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine (FDOPA)-PET/MRI to define tumor volumes compared to MRI alone more accurately, assessed its role in patient management, and correlated PET findings with histopathology.

Methods: Ten patients with known or suspected gliomas underwent standard of care surgical resection and/or stereotactic biopsy.

Utility of F-Fluciclovine PET/MRI for Staging Newly Diagnosed High-Risk Prostate Cancer and Evaluating Response to Initial Androgen Deprivation Therapy: A Prospective Single-Arm Pilot Study.

Despite advances in prostate cancer treatment, rates of biochemical recurrence remain high, relating to lack of detection of small-volume metastatic disease using conventional imaging for initial staging. The purpose of this study was to assess the potential use of F-fluciclovine PET/MRI for initial staging of high-risk prostate cancer and evaluating response to androgen deprivation therapy (ADT). This prospective clinical trial enrolled 14 men with newly diagnosed high-risk prostate cancer and negative or equivocal conventional staging imaging for metastatic disease between January 2018 and February 2019.