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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. Similarly to other oncometabolites, L-2HG has the potential to profoundly impact gene expression. Here, we demonstrate that L-2HG remodels amino acid metabolism in renal cancer cells through combined effects on histone methylation and RNA [N.sup.6]- methyladenosine. The combined effects of L-2HG result in a metabolic liability that renders tumors cells reliant on exogenous serine to support proliferation, redox homeostasis, and tumor growth. In concert with these data, high-L-2HG kidney cancers demonstrate reduced expression of multiple serine biosynthetic enzymes. Collectively, our data indicate that high-L-2HG renal tumors could be specifically targeted by strategies that limit serine availability to tumors., Introduction Oncometabolites are small molecules that aberrantly accumulate within tumor cells. These small molecules can have either tumor-promoting or -suppressive effects, indicating that their impact on tumor biology is highly [...]

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., plastic) into electron density maps. Over the last decade, a plethora of novel MRI-based algorithms has been developed to more accurately derive the attenuation properties of the human head, including the skull. Although promising, none of these techniques has yet emerged as an optimal and universally adopted strategy for AC in PET/MRI. In this work, we propose a path for PET/MRI qualification for multicenter brain imaging studies. Specifically, our solution is to separate the head AC from the other factors that affect PET data quantification and use a patient as a phantom to assess the former. The emission data collected on the integrated PET/MRI scanner to be qualified should be reconstructed using both MRI- and CT-based AC methods, and whole-brain qualitative and quantitative (both voxelwise and regional) analyses should be performed. The MRI-based approach will be considered satisfactory if the PET quantification bias is within the acceptance criteria specified here. We have implemented this approach successfully across 2 PET/MRI scanner manufacturers at 2 sites.

[89Zr]Oxinate4 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 [89Zr]Oxinate4 for human use. In this report, we describe the detailed production of [89Zr]Oxinate4 under USP <823> and autologous leukocyte radiolabeling under USP <797>. The final product presented high radiochemical purity and stability at 24 h post synthesis (>99%) and passed in all quality control assays required for clinical use. [89Zr]Oxinate4 did not compromise the white blood cells viability and did not show considerable cellular efflux up to 3 h post labeling. The translation of this technique into human use can provide insight into several disease mechanisms since [89Zr]Oxinate4 has the potential to label any cell subset of interest. [ABSTRACT FROM AUTHOR]

Positron emission tomography using the fluorine-18 (18F) fluciclovine radiotracer has been approved for use in recurrent prostate cancer and is a useful tool for clinical decision making. However, 18F-fluciclovine is not specific for prostate cancer tumor cells, and false-positive results have been reported. In the present study, we have reported our experience with synchronous malignancies identified using 18F-fluciclovine and reviewed other reported cases, with a special emphasis on highlighting the clinical decisions that led to the correct diagnosis. [ABSTRACT FROM AUTHOR]

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. FDOPA-PET/MRI was performed prior to surgery, allowing for precise co-registration of PET, MR, and biopsies. The biopsy sites were modeled as 5-mm spheres, and the local FDOPA uptake at each site was determined. Correlations were performed between measures of tumor histopathology, and static and dynamic PET values: standardized uptake values (SUVs), tumor to brain ratios, metabolic tumor volumes, and tracer kinetics at volumes of interest (VOIs) and biopsy sites. Results Tumor FDOPA-PET uptake was visualized in 8 patients. In 2 patients, tracer uptake was similar to normal brain reference with no histological findings of malignancy. Eight biopsy sites confirmed for glioma had FDOPA uptake without T1 contrast enhancement. The PET parameters were highly correlated only with the cell proliferation marker, Ki-67 (SUVmax: r = 0.985, P  = .002). In this study, no statistically significant difference between high-grade and low-grade tumors was demonstrated. The dynamic PET analysis of VOIs and biopsy sites showed decreasing time-activity curves patterns. FDOPA-PET imaging directly influenced patient management. Conclusions Simultaneous FDOPA-PET/MRI allowed for more accurate visualization and delineation of gliomas, enabling more appropriate patient management and simplified validation of PET findings with histopathology. [ABSTRACT FROM AUTHOR]

Abstract: 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. Group (FM vs HC) was the main predictor of interest and TSPO binding status (high- vs mixed-affinity) was added as a covariate. The FM group had higher V T in the right postcentral gyrus ( b = 0.477, P = 0.033), right occipital gray matter (GM; b = 0.438, P = 0.039), and the right temporal GM ( b = 0.466, P = 0.042). The FM group also had lower V T than HCs in the left isthmus of the cingulate gyrus ( b = -0.553, P = 0.014). In the subgroup of high-affinity binders, the FM group had higher V T in the bilateral precuneus, postcentral gyrus, parietal GM, occipital GM, and supramarginal gyrus. Group differences in the right parietal GM were associated with decreased quality of life, higher pain severity and interference, and cognitive problems. In support of our hypothesis, we found increased radioligand binding (V T ) in the FM group compared with HCs in several brain regions regardless of participants' TSPO binding status. The ROIs overlapped with prior reports of increased TSPO binding in FM. Overall, increasing evidence supports the hypothesis that FM involves microglia-mediated neuroinflammation in the brain., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

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. FDOPA-PET/MRI was performed prior to surgery, allowing for precise co-registration of PET, MR, and biopsies. The biopsy sites were modeled as 5-mm spheres, and the local FDOPA uptake at each site was determined. Correlations were performed between measures of tumor histopathology, and static and dynamic PET values: standardized uptake values (SUVs), tumor to brain ratios, metabolic tumor volumes, and tracer kinetics at volumes of interest (VOIs) and biopsy sites., Results: Tumor FDOPA-PET uptake was visualized in 8 patients. In 2 patients, tracer uptake was similar to normal brain reference with no histological findings of malignancy. Eight biopsy sites confirmed for glioma had FDOPA uptake without T1 contrast enhancement. The PET parameters were highly correlated only with the cell proliferation marker, Ki-67 (SUV max : r = 0.985, P  = .002). In this study, no statistically significant difference between high-grade and low-grade tumors was demonstrated. The dynamic PET analysis of VOIs and biopsy sites showed decreasing time-activity curves patterns. FDOPA-PET imaging directly influenced patient management., Conclusions: Simultaneous FDOPA-PET/MRI allowed for more accurate visualization and delineation of gliomas, enabling more appropriate patient management and simplified validation of PET findings with histopathology., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: The aim of this study was to report the treatment planning feasibility of dose escalation to suspicious lymph nodes (LNs) for a series of men who underwent pretreatment [ 18 F]fluciclovine positron emission tomography (PET)/magnetic resonance imaging (MRI)., Methods and Materials: Cases of men with prostate cancer who enrolled in a clinical trial of pretreatment [ 18 F]fluciclovine PET who had suspicious LNs were selected. Pelvic LNs <1 cm were defined as positive based on [ 18 F]fluciclovine-PET if their maximum standardized uptake value (SUV max ) was ≥1.3-fold greater than the reference blood pool SUV mean , and LNs ≥1 cm were defined as positive if the SUV was greater than the reference SUV bone marrow reference. For each case, a radiation treatment plan was generated to deliver 70 Gy to the prostate and proximal seminal vesicles, 60.2 Gy to the PET-positive LNs, and 50.4 Gy to the elective nodal regions, simultaneously in 28 fractions of 2.5 Gy, 2.15 Gy, and 1.8 Gy, respectively. Treatment planning goals were defined a priori. The resulting target volume and organ-at-risk dosimetry were compared with the original treatment plan., Results: Four cases were identified, with between 1 and 5 [ 18 F]fluciclovine PET-positive LNs each. Goals for the prostate and elective nodal target volumes were successfully met in all cases. The goal of covering more than 90% of the positive LN planning target volume by the prescription dose of 60.2 Gy was met in 3 of the 4 cases. This goal was not met in 1 case, but 100% of clinical target volume was covered by 60.2 Gy. The primary organ-at-risk tradeoff was that a small volume (0.5-8.2 cm 3 ) of small bowel would receive ≥54 Gy in each case., Conclusions: These preliminary results suggest that [ 18 F]fluciclovine PET/MRI directed dose escalation of suspicious pelvic LNs is likely feasible in the setting of definitive radiation therapy. The potential clinical benefit of dose escalating [ 18 F]fluciclovine PET-positive LNs should be investigated in a prospective clinical trial., (© 2019 The Author(s).)