scholarly journals Detection of Remote Neuronal Reactions in the Thalamus and Hippocampus Induced by Rat Glioma Using the PET Tracer Cis-4-[18F]Fluoro-D-Proline

2013 ◽  
Vol 33 (5) ◽  
pp. 724-731 ◽  
Author(s):  
Stefanie Geisler ◽  
Antje Willuweit ◽  
Michael Schroeter ◽  
Karl Zilles ◽  
Kurt Hamacher ◽  
...  
Keyword(s):  
Ex Vivo ◽  
High Sensitivity ◽  
Brain Regions ◽  
Tracer Uptake ◽  
Thalamic Nuclei ◽  
Brain Areas ◽  
Rat Glioma ◽  
F98 Rat Glioma ◽  
Pet Tracer ◽  
Positron Emission

After cerebral ischemia or trauma, secondary neurodegeneration may occur in brain regions remote from the lesion. Little is known about the capacity of cerebral gliomas to induce secondary neurodegeneration. A previous study showed that cis-4-[18F]fluoro-D-proline (D- cis-[18F]FPro) detects secondary reactions of thalamic nuclei after cortical infarction with high sensitivity. Here we investigated the potential of D- cis-[18F]FPro to detect neuronal reactions in remote brain areas in the F98 rat glioma model using ex vivo autoradiography. Although the tumor tissue of F98 gliomas showed no significant D- cis-[18F]FPro uptake, we observed prominent tracer uptake in 7 of 10 animals in the nuclei of the ipsilateral thalamus, which varied with the specific connectivity with the cortical areas affected by the tumor. In addition, strong D- cis-[18F]FPro accumulation was noted in the hippocampal area CA1 in two animals with ipsilateral F98 gliomas involving hippocampal subarea CA3 rostral to that area. Furthermore, focal D- cis-[18F]FPro uptake was present in the necrotic center of the tumors. Cis-4-[18F]fluoro-D-proline uptake was accompanied by microglial activation in the thalamus, in the hippocampus, and in the necrotic center of the tumors. The data suggest that brain tumors induce secondary neuronal reactions in remote brain areas, which may be detected by positron emission tomography (PET) using D- cis-[18F]FPro.

scholarly journals Synthesis and Biological Evaluation of a Radiolabeled PET Probe for Visualization of In Vivo α-Fucosidase Expression

2021 ◽  
Vol 14 (8) ◽  
pp. 745
Author(s):  
Jonathan Cotton ◽  
Chris Marc Goehring ◽  
Anna Kuehn ◽  
Andreas Maurer ◽  
Kerstin Fuchs ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Sodium Hydride ◽  
Biological Evaluation ◽  
Tracer Uptake ◽  
Mouse Serum ◽  
Molar Activity ◽  
Pet Tracer ◽  
Positron Emission

The acidic hydrolase α-fucosidase (AF) is a biomarker for maladies such as cancer and inflammation. The most advanced probes for α-fucosidase are unfortunately constrained to ex vivo or in vitro applications. The in vivo detection and quantification of AF using positron emission tomography would allow for better discovery and diagnosis of disease as well as provide better understanding of disease progression. We synthesized, characterized, and evaluated a radiolabeled small molecule inhibitor of AF based on a known molecule. The radiosynthesis involved the 11C methylation of a phenoxide, which was generated in situ by ultrasonification of the precursor with sodium hydride. The tracer was produced with a decay corrected yield of 41.7 ± 16.5% and had a molar activity of 65.4 ± 30.3 GBq/μmol. The tracer was shown to be stable in mouse serum at 60 min. To test the new tracer, HCT116 colorectal carcinoma cells were engineered to overexpress human AF. In vitro evaluation revealed 3.5-fold higher uptake in HCT116AF cells compared to HCT116 controls (26.4 ± 7.8 vs. 7.5 ± 1.0 kBq/106 cells). Static PET scans 50 min post injection revealed 2.5-fold higher tracer uptake in the HCT116AF tumors (3.0 ± 0.8%ID/cc (n = 6)) compared with the controls (1.2 ± 0.8 (n = 5)). Dynamic scans showed higher uptake in the HCT116AF tumors at all time-points (n = 2). Ex vivo analysis of the tumors, utilizing fluorescent DDK2 antibodies, confirmed the expression of human AF in the HCT116AF xenografts. We have developed a novel PET tracer to image AF in vivo and will now apply this to relevant disease models.

Integrated positron emission tomography and magnetic resonance imaging–guided resection of brain tumors: a report of 103 consecutive procedures

2006 ◽  
Vol 104 (2) ◽  
pp. 238-253 ◽  
Author(s):  
Benoît Pirotte ◽  
Serge Goldman ◽  
Olivier Dewitte ◽  
Nicolas Massager ◽  
David Wikler ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Brain Tumors ◽  
Mr Imaging ◽  
Tumor Resection ◽  
Tracer Uptake ◽  
Emission Tomography ◽  
Mr Images ◽  
Pet Tracer ◽  
Positron Emission ◽  
Pet Scanning

Object The aim of this study was to evaluate the integration of positron emission tomography (PET) scanning data into the image-guided resection of brain tumors. Methods Positron emission tomography scans obtained using fluorine-18 fluorodeoxyglucose (FDG) and l-[methyl-11C]methionine (MET) were combined with magnetic resonance (MR) images in the navigational planning of 103 resections of brain tumors (63 low-grade gliomas [LGGs] and 40 high-grade gliomas [HGGs]). These procedures were performed in 91 patients (57 males and 34 females) in whom tumor boundaries could not be accurately identified on MR images for navigation-based resection. The level and distribution of PET tracer uptake in the tumor were analyzed to define the lesion contours, which in turn yielded a PET volume. The PET scanning–demonstrated lesion volume was subsequently projected onto MR images and compared with MR imaging data (MR volume) to define a final target volume for navigation-based resection—the tumor contours were displayed in the microscope’s eyepiece. Maximal tumor resection was accomplished in each case, with the intention of removing the entire area of abnormal metabolic activity visualized during surgical planning. Early postoperative MR imaging and PET scanning studies were performed to assess the quality of tumor resection. Both pre- and postoperative analyses of MR and PET images revealed whether integrating PET data into the navigational planning contributed to improved tumor volume definition and tumor resection. Metabolic information on tumor heterogeneity or extent was useful in planning the surgery. In 83 (80%) of 103 procedures, PET studies contributed to defining a final target volume different from that obtained with MR imaging alone. Furthermore, FDG-PET scanning, which was performed in a majority of HGG cases, showed that PET volume was less extended than the MR volume in 16 of 21 cases and contributed to targeting the resection to the hypermetabolic (anaplastic) area in 11 (69%) of 16 cases. Performed in 59 LGG cases and 23 HGG cases, MET-PET demonstrated that the PET volume did not match the MR volume and improved the tumor volume definition in 52 (88%) of 59 and 18 (78%) of 23, respectively. Total resection of the area of increased PET tracer uptake was achieved in 54 (52%) of 103 procedures. Conclusions Imaging guidance with PET scanning provided independent and complementary information that helped to assess tumor extent and plan tumor resection better than with MR imaging guidance alone. The PET scanning guidance could help increase the amount of tumor removed and target image-guided resection to tumor portions that represent the highest evolving potential.

Evaluation of glucagon-like peptide-1 receptor expression in non-diabetic and diabetic atherosclerotic mice using PET tracer 68Ga-NODAGA-exendin-4

2021 ◽  
Author(s):  
Mia Ståhle ◽  
Sanna Hellberg ◽  
Jenni Virta ◽  
Heidi Liljenbäck ◽  
Olli Metsälä ◽  
...  
Keyword(s):  
Vessel Wall ◽  
Vascular Inflammation ◽  
Tracer Uptake ◽  
Receptor Expression ◽  
Atherosclerotic Lesions ◽  
Pet Tracer ◽  
Positron Emission ◽  
Healthy Control ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Activation of glucagon-like peptide-1 receptor (GLP-1R) signaling attenuates development of atherosclerosis and vascular inflammation. However, the expression of GLP-1R in atherosclerotic arteries remains uncertain. We evaluated whether a positron emission tomography (PET) tracer 68Ga-NODAGA-exendin-4 enables detection and imaging of GLP-1R expression in the mouse atherosclerotic aorta. Hypercholesterolemic (LDLR-/-ApoB100/100), hypercholesterolemic and diabetic (IGF-II/LDLR-/-ApoB100/100) as well as healthy control (C57BL/6N) mice were utilized in the study. The uptake of 68Ga-NODAGA-exendin-4 in atherosclerotic lesions was studied by autoradiography of tissue sections followed by immunofluorescence evaluation of inflammatory and vascular cell markers and GLP-1R. A subset of mice was imaged with 68Ga-NODAGA-exendin-4 PET/computed tomography (CT). The aortas of both LDLR-/-ApoB100/100 and IGF-II/LDLR-/-ApoB100/100 mice contained prominent, macrophage-rich atherosclerotic lesions. Diabetic mice demonstrated hyperglycemia and glucose intolerance. We found that by autoradiography, 68Ga-NODAGA-exendin-4 uptake was focally increased in macrophage-rich lesion areas compared with corresponding healthy vessel wall (lesion-to-wall ratio 1.6 ± 0.10, p<0.0001) in both non-diabetic and diabetic hypercholesterolemic mice. Pre-injection of unlabeled exendin-4 peptide significantly reduced cellular uptake of 68Ga-NODAGA-exendin-4. Furthermore, PET/CT imaging showed 68Ga-NODAGA-exendin-4 accumulation in the atherosclerotic aorta. Immunofluorescence stainings demonstrated co-localization of GLP-1R with macrophage-rich areas in atherosclerotic lesions. Tracer uptake was low in the healthy vessel wall of C57BL/6N mice coupled with negative GLP-1R staining. In conclusion, 68Ga-NODAGA-exendin-4 detects GLP-1R expression in atherosclerotic lesions in both non-diabetic and diabetic hypercholesterolemic mice. These results provide evidence that GLP-1R expression is mainly localized in macrophage-rich area in atherosclerotic lesions and may have implications for studies of pharmacological modification of GLP-1R signaling in atherosclerosis.

scholarly journals Imaging and Methotrexate Response Monitoring of Systemic Inflammation in Arthritic Rats Employing the Macrophage PET Tracer [18F]Fluoro-PEG-Folate

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Durga M. S. H. Chandrupatla ◽  
Gerrit Jansen ◽  
Elise Mantel ◽  
Philip S. Low ◽  
Takami Matsuyama ◽  
...  
Keyword(s):  
Systemic Inflammation ◽  
Pet Imaging ◽  
Ex Vivo ◽  
Folate Receptor ◽  
Tracer Uptake ◽  
Response Monitoring ◽  
Distribution Analysis ◽  
Pet Tracer ◽  
Systemic Inflammatory Disease ◽  
Before And After

Background. In rheumatoid arthritis, articular inflammation is a hallmark of disease, while the involvement of extra-articular tissues is less well defined. Here, we examined the feasibility of PET imaging with the macrophage tracer [18F]fluoro-PEG-folate, targeting folate receptorβ(FRβ), to monitor systemic inflammatory disease in liver and spleen of arthritic rats before and after methotrexate (MTX) treatment.Methods. [18F]Fluoro-PEG-folate PET scans (60 min) were acquired in saline- and MTX-treated (1 mg/kg, 4x) arthritic rats, followed by tissue resection and radiotracer distribution analysis. Liver and spleen tissues were stained for ED1/ED2-macrophage markers and FRβexpression.Results. [18F]Fluoro-PEG-folate PET and ex vivo tissue distribution studies revealed a significant (p<0.01) 2-fold lower tracer uptake in both liver and spleen of MTX-treated arthritic rats. Consistently, ED1- and ED2-positive macrophages were significantly (p<0.01) decreased in liver (4-fold) and spleen (3-fold) of MTX-treated compared with saline-treated rats. Additionally, FRβ-positive macrophages were also significantly reduced in liver (5-fold,p<0.005) and spleen (3-fold,p<0.01) of MTX- versus saline-treated rats.Conclusions. MTX treatment reduced activated macrophages in liver and spleen, as markers for systemic inflammation in these organs. Macrophage PET imaging with [18F]fluoro-PEG-folate holds promise for detection of systemic inflammation in RA as well as therapy (MTX) response monitoring.

Music, Maestro, Please: Thalamic multisensory integration in music perception, processing and production

2019 ◽  
Vol 11 (2) ◽  
pp. 98
Author(s):  
Artur Jaschke
Keyword(s):  
Multisensory Integration ◽  
Music Perception ◽  
Initial Point ◽  
Initial Step ◽  
Brain Regions ◽  
Thalamic Nuclei ◽  
Brain Areas ◽  
Neural Connections ◽  
Parietal Lobes ◽  
The Brain

Music activates a wide array of brain areas involved in different functions such as   perception, processing and execution of music. Understanding musical processes in the brain has multiple implications in the neuro- and health sciences.  Challenging the brain with a multisensory stimulus such as music activates responses beyond the auditory cortex of the temporal lobe. Other areas that are involved include the frontal lobes, parietal lobes, areas of the limbic system such as the amygdala, hippocampus and thalamus, the cerebellum and the brainstem. Nonetheless, there has been no attempt to summarize all involved brain areas in music into one overall encompassing map. This may well be, as there has been no thorough theory introduced, which would allow an initial point of departure in creating such a mapTherefore, a thorough systematic review has been conducted to identify all mentioned neural connections involved in the perception, processing and execution of music.  Communication between the thalamic nuclei is the initial step in multisensory integration, which lies at the base of the neural networks as proposed in this paper. Against this background, this manuscript introduces the to our knowledge first map of all brain regions involved in the perception, processing and execution of music.Consequently, placing thalamic multisensory integration at the core of this atlas allowed us to create a preliminary theory to explain the complexity of music induced brain activation.

scholarly journals [18F]-T807 tauopathy PET imaging in chronic traumatic encephalopathy

F1000Research ◽  
2014 ◽  
Vol 3 ◽  
pp. 229 ◽  
Author(s):  
Sam Gandy ◽  
Steven T. DeKosky
Keyword(s):  
Pet Imaging ◽  
Brain Injuries ◽  
Chronic Traumatic Encephalopathy ◽  
Neurofibrillary Tangle ◽  
Brain Regions ◽  
Tracer Uptake ◽  
Positron Emission ◽  
Molecular Ligand ◽  
Mesial Temporal Lobe ◽  
Recent Case Report

A new molecular ligand for positron emission tomography (PET) of the human brain, [18F]-T807, is under investigation for the antemortem detection of pathological neurofibrillary aggregates, which are evidence of neurofibrillary tangle (NFT) diseases, also known as tauopathies. Repetitive mild traumatic brain injuries in athletes and battlefield veterans are associated with one such tauopathy, known as chronic traumatic encephalopathy (CTE). In a recent case report, a former NFL player with clinically probable CTE and a concurrent Progressive Supranuclear Palsy (PSP) –like syndrome was studied using [18F]-T807. The interpretation of this player’s [18F]-T807 PET imaging was complicated by the overlap of tracer uptake in brain regions involved in CTE and PSP with regions associated with either nonspecific [18F]-T807 ligand binding or “aging-associated” binding of [18F]-T807 to authentic tauopathy known to be associated with aging and disease severity (i.e., NFT in the mesial temporal lobe). The implications of these data for the utility of [18F]-T807 in the pre-mortem detection of CTE are summarized.

scholarly journals Design, Synthesis, Computational, and Preclinical Evaluation of natTi/45Ti-Labeled Urea-Based Glutamate PSMA Ligand

Molecules ◽  
2020 ◽  
Vol 25 (5) ◽  
pp. 1104 ◽  
Author(s):  
Kristina Søborg Pedersen ◽  
Christina Baun ◽  
Karin Michaelsen Nielsen ◽  
Helge Thisgaard ◽  
Andreas Ingemann Jensen ◽  
...  
Keyword(s):  
Computer Aided Design ◽  
Ex Vivo ◽  
Design Synthesis ◽  
Psma Ligand ◽  
Pet Tracer ◽  
Positron Emission ◽  
Tumor Accumulation ◽  
Aided Design

Despite promising anti-cancer properties in vitro, all titanium-based pharmaceuticals have failed in vivo. Likewise, no target-specific positron emission tomography (PET) tracer based on the radionuclide 45Ti has been developed, notwithstanding its excellent PET imaging properties. In this contribution, we present liquid–liquid extraction (LLE) in flow-based recovery and the purification of 45Ti, computer-aided design, and the synthesis of a salan-natTi/45Ti-chelidamic acid (CA)-prostate-specific membrane antigen (PSMA) ligand containing the Glu-urea-Lys pharmacophore. The compound showed compromised serum stability, however, no visible PET signal from the PC3+ tumor was seen, while the ex vivo biodistribution measured the tumor accumulation at 1.1% ID/g. The in vivo instability was rationalized in terms of competitive citrate binding followed by Fe(III) transchelation. The strategy to improve the in vivo stability by implementing a unimolecular ligand design is presented.

POSITRON EMISSION TOMOGRAPHY-GUIDED VOLUMETRIC RESECTION OF SUPRATENTORIAL HIGH-GRADE GLIOMAS

Neurosurgery ◽  
2009 ◽  
Vol 64 (3) ◽  
pp. 471-481 ◽  
Author(s):  
Benoit J.M. Pirotte ◽  
Marc Levivier ◽  
Serge Goldman ◽  
Nicolas Massager ◽  
David Wikler ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Contrast Enhancement ◽  
Tumor Resection ◽  
Tracer Uptake ◽  
Mri Contrast ◽  
Postoperative Mri ◽  
Anaplastic Gliomas ◽  
Pet Tracer ◽  
Positron Emission ◽  
Mri Scans

Abstract OBJECTIVE Integrating positron emission tomographic (PET) images into the image-guided resection of high-grade gliomas (HGG) has shown that metabolic information on tumor heterogeneity and distribution are useful for planning surgery, improve tumor delineation, and provide a final target contour different from that obtained with magnetic resonance imaging (MRI) alone in about 80% of the procedures. Moreover, PET guidance helps to increase the amount of tumor removed and to target image-guided resection to anaplastic tissue areas. The present study aims to evaluate whether PET-guided volumetric resection (VR) in supratentorial HGG might add benefit to the patient's outcome. METHODS PET images using [18F]fluorodeoxyglucose (n=23) and [11C]methionine (n=43) were combined with MRI scans in the planning of VR procedures performed at the initial stage in 66 consecutive patients (43 M/23 F) with supratentorial HGG according to the technique previously described. In all cases (35 anaplastic gliomas [20 astrocytomas, 10 oligoastrocytomas, 5 oligodendrogliomas] and 31 glioblastomas [GBM]), level and distribution of PET tracer uptake were analyzed to define a PET contour projected on MRI scans to define a final target contour for VR. Maximal tumor resection was accomplished in each case, with the intention to remove the entire abnormal metabolic area comprised in the surgical planning. Early postoperative MRI and PET assessed tumor resection. Survival analysis was performed separately in anaplastic gliomas and glioblastoma multiforme according to the presence or absence of residual tracer uptake on postoperative PET and according to the presence or absence of residual contrast enhancement on postoperative MRI. RESULTS Preoperatively, metabolic information helped the surgical planning. In all procedures, PET contributed to define a final target contour different from that obtained with MRI alone. Postoperatively, 46 of 66 patients had no residual PET tracer uptake (total PET resection), 23 of 66 had no residual MRI contrast enhancement. No additional neurological morbidity due to the technique was reported. A total PET tracer uptake resection was associated with a significantly longer survival in anaplastic gliomas (P = 0.0071) and in glioblastoma multiforme (P = 0.0001), respectively. A total MRI contrast enhancement resection was not correlated with a significantly better survival, neither in anaplastic gliomas (P = 0.6089) nor in glioblastoma multiforme (P = 0.6806). CONCLUSIONS Complete resection of the increased PET tracer uptake prolongs the survival of HGG patients. Because PET information represents a more specific marker than MRI enhancement for detecting anaplastic tumor tissue, PET-guidance increases the amount of anaplastic tissue removed in HGG.

scholarly journals Reproducible Analysis of Rat Brain PET Studies Using an Additional [18F]NaF Scan and an MR-Based ROI Template

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Hans J. C. Buiter ◽  
Floris H. P. van Velden ◽  
Josée E. Leysen ◽  
Abraham Fisher ◽  
Albert D. Windhorst ◽  
...  
Keyword(s):  
Rat Brain ◽  
Ex Vivo ◽  
Correlation Coefficients ◽  
Brain Regions ◽  
Image Coregistration ◽  
Brain Pet ◽  
Biodistribution Data ◽  
Positron Emission ◽  
Reproducible Analysis ◽  
Uptake Data

Background. An important step in the analysis of positron emission tomography (PET) studies of the brain is the definition of regions of interest (ROI). Image coregistration, ROI analysis, and quantification of brain PET data in small animals can be observer dependent. The purpose of this study was to investigate the feasibility of ROI analysis based on a standard MR template and an additional [18F]NaF scan. Methods. [18F]NaF scans of 10 Wistar rats were coregistered with a standard MR template by 3 observers and derived transformation matrices were applied to corresponding [11C]AF150(S) images. Uptake measures were derived for several brain regions delineated using the MR template. Overall agreement between the 3 observers was assessed by interclass correlation coefficients (ICC) of uptake data. In addition, [11C]AF150(S) ROI data were compared with ex vivo biodistribution data. Results. For all brain regions, ICC analysis showed excellent agreement between observers. Reproducibility, estimated by calculation of standard deviation of the between-observer differences, was demonstrated by an average of 17% expressed as coefficient of variation. Uptake of [11C]AF150(S) derived from ROI analysis closely matched ex vivo biodistribution data. Conclusions. The proposed method provides a reproducible and tracer-independent method for ROI analysis of rat brain PET data.

scholarly journals In Vivo Imaging of Local Inflammation: Monitoring LPS-Induced CD80/CD86 Upregulation by PET

2020 ◽  
Author(s):  
Marco F. Taddio ◽  
Claudia A. Castro Jaramillo ◽  
Peter Runge ◽  
Alain Blanc ◽  
Claudia Keller ◽  
...  
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
Ex Vivo ◽  
Tracer Uptake ◽  
Local Inflammation ◽  
Inoculation Site ◽  
Positron Emission ◽  
Pet Ct ◽  
Antigen Presenting

Abstract Purpose The co-stimulatory molecules CD80 and CD86 are upregulated on activated antigen-presenting cells (APC). We investigated whether local APC activation, induced by subcutaneous (s.c.) inoculation of lipopolysaccharides (LPS), can be imaged by positron emission tomography (PET) with CD80/CD86-targeting 64Cu-labelled abatacept. Procedures Mice were inoculated s.c. with extracellular-matrix gel containing either LPS or vehicle (PBS). Immune cell populations were analysed by flow cytometry and marker expression by RT-qPCR. 64Cu-NODAGA-abatacept distribution was analysed using PET/CT and ex vivo biodistribution. Results The number of CD80+ and CD86+ immune cells at the LPS inoculation site significantly increased a few days after inoculation. CD68 and CD86 expression were higher at the LPS than the PBS inoculation site, and CD80 was only increased at the LPS inoculation site. CTLA-4 was highest 10 days after LPS inoculation, when CD80/CD86 decreased again. A few days after inoculation, 64Cu-NODAGA-abatacept distribution to the inoculation site was significantly higher for LPS than PBS (4.2-fold). Co-administration of unlabelled abatacept or human immunoglobulin reduced tracer uptake. The latter reduced the number of CD86+ immune cells at the LPS inoculation site. Conclusions CD80 and CD86 are upregulated in an LPS-induced local inflammation, indicating invasion of activated APCs. 64Cu-NODAGA-abatacept PET allowed following APC activation over time.

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