scholarly journals Decreased Cortical Serotonin in Neonatal Rabbits Exposed to Endotoxin in Utero

2010 ◽  
Vol 31 (2) ◽  
pp. 738-749 ◽  
Author(s):  
Sujatha Kannan ◽  
Fadoua Saadani-Makki ◽  
Bindu Balakrishnan ◽  
Hui Dai ◽  
Pulak K Chakraborty ◽  
...  
Keyword(s):  
Somatosensory Cortex ◽  
Neurodevelopmental Disorders ◽  
Somatosensory System ◽  
Fold Increase ◽  
Standard Uptake Value ◽  
Perinatal Period ◽  
Newborn Brain ◽  
Positron Emission ◽  
Parietal Cortices

Maternal intrauterine inflammation is implicated in neurodevelopmental disorders in the offspring. Serotonin is crucial for regulating maturation in the developing brain, and maternal inflammation may result in disruption of the serotonergic system in the perinatal period. Saline or endotoxin was injected intrauterine in pregnant rabbits term. Newborn rabbits underwent positron emission tomography (PET) imaging with α[11C]methyl-l-tryptophan (AMT) to evaluate tryptophan metabolism in vivo. Decrease in standard uptake value for AMT and decrease in serotonin concentration was noted in the frontal and parietal cortices of endotoxin kits when compared with controls. In addition, a significant decrease in serotonin-immunoreactive fibers and decreased expression of serotonin transporter (5HTT) was measured in the somatosensory cortex. There was a three-fold increase in the number of apoptotic cells in the ventrobasal (VB) thalamus without loss of raphe serotonergic cell bodies in endotoxin kits when compared with controls. Glutamateric VB neurons projecting to somatosensory cortex transiently express 5HTT and store serotonin, regulating development of the somatosensory cortex. Intrauterine inflammation results in alterations in cortical serotonin and disruption of serotonin-regulated thalamocortical development in the newborn brain. This may be a common link in neurodevelopmental disorders resulting in impairment of the somatosensory system, such as cerebral palsy and autism.

Abstract 35: DVT Inflammation Assessed by 18F-FDG-PET/CT Predicts Subsequent Vein Wall Scarring

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Chase W Kessinger ◽  
Ahmed Tawakol ◽  
Gregory R Wojtkiewicz ◽  
Peter K Henke ◽  
Ralph Weissleder ◽  
...  
Keyword(s):  
Fdg Pet ◽  
Vena Cava ◽  
Standard Uptake Value ◽  
Vein Wall ◽  
Positron Emission ◽  
Pet Ct ◽  
18F Fdg ◽  
The Right ◽  
Fdg Pet Ct

Objective: While venous thrombosis (VT)-induced inflammation facilitates thrombus resolution, inflammation causes vein wall scarring (VWS). Recently, statins have shown to improve VT resolution and reduce VT inflammatory components. In this study, we hypothesized that early VT inflammation detected by 18F-FDG positron emission tomography/computed tomography (PET/CT) could predict subsequent late stage VWS, and would be attenuated by statin therapy. Methods: Stasis VT was induced in 8-12 week old male C57BL/6 mice (n=31) in either the right jugular vein (n=13) or inferior vena cava (IVC,n=18). Animals in the IVC VT cohort were randomized to statin (n=8) or control (n=10) treatment. Statin, rosuvastatin (5mg/kg), was administered by oral gavage, daily starting 24 hours prior to VT induction; control mice received saline. All mice underwent survival FDG-PET/CT venography imaging on day 2. FDG inflammation signals (standard uptake value=SUV) were measured in the thrombosed vein and compared to the sham-operated venous segments or treatment control. On day 14, mice were sacrificed and VT tissue was resected. Picrosirius red staining allowed measurement of collagen and vein wall thickness in VT sections. Results: FDG-PET/CT at day 2 revealed increased inflammation signal activity in jugular VT (SUV 1.43 ± 0.3 VT vs. 0.81 ± 0.3 contralateral vein, p<0.0001). Statin-treated mice showed a trend of decreased inflammation signal at day 2 in the IVC VT models (SUV 1.02 ± 0.1 statin VT vs. 1.42 ± 0.2 control VT, p=0.07). Day 14 histological analysis revealed significantly reduced vein wall injury in statin-treated animals (thickness, 32±9.4 μm statin; vs. 56.2±14.7 μm control, p=0.02). Day 2 FDG-PET inflammation in VT correlated positively with the magnitude of day 14 VWS (jugular VT, Spearman r=0.62, p=0.02; IVC VT r=0.74, p<0.001, respectively). Conclusions: Quantitative FDG-PET/CT imaging demonstrates that early in vivo VT inflammation predicts subsequent VWS, a driver of post-thrombotic syndrome (PTS). The overall findings strengthen: (i) the link between inflammation and PTS; (ii) the translational potential of FDG-PET inflammation to predict VWS and PTS; and (iii) the concept that statins and other anti-inflammatory therapies could reduce VWS and PTS.

scholarly journals Measurement of Changes in Opioid Receptor Binding in Vivo During Trigeminal Neuralgic Pain Using [11C]Diprenorphine and Positron Emission Tomography

1999 ◽  
Vol 19 (7) ◽  
pp. 803-808 ◽  
Author(s):  
Anthony K. P. Jones ◽  
Niel D. Kitchen ◽  
Hiroshi Watabe ◽  
Vincent J. Cunningham ◽  
Terry Jones ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Volume Of Distribution ◽  
Emission Tomography ◽  
Subcortical Structures ◽  
Endogenous Opioid ◽  
Positron Emission ◽  
Before And After ◽  
Pain State ◽  
Parietal Cortices

The binding of [11C]diprenorphine to µ, κ, and Δ subsites in cortical and subcortical structures was measured by positron emission tomography in vivo in six patients before and after surgical relief of trigeminal neuralgia pain. The volume of distribution of [11C]diprenorphine binding was significantly increased after thermocoagulation of the relevant trigeminal division in the following areas: prefrontal, insular, perigenual, mid-cingulate and inferior parietal cortices, basal ganglia, and thalamus bilaterally. In addition to the pain relief associated with the surgical procedure, there also was an improvement in anxiety and depression scores. In the context of other studies, these changes in binding most likely resulted from the change in the pain state. The results suggest an increased occupancy by endogenous opioid peptides during trigeminal pain but cannot exclude coexistent down-regulation of binding sites.

Determining androgen inactivation status in prostate cancer by [18F] DHT PET.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 191-191
Author(s):  
Ziqi Zhu ◽  
Yoon-Mi Chung ◽  
Olga Sergeeva ◽  
Vladimir Kepe ◽  
Michael Berk ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Retention Rate ◽  
Xenograft Model ◽  
Treatment Resistance ◽  
Fold Increase ◽  
Standard Uptake Value ◽  
Retention Rates ◽  
Castration Resistant Prostate Cancer ◽  
Pet Ct

191 Background: Castration-resistant prostate cancer occurs in part due to increased tumor tissue testosterone (T) and dihydrotestosterone (DHT) that sustain tumor growth. T and DHT are converted to inactive T- and DHT-glucuronide (T/DHT-G) by uridine 5'-diphospho-glucuronosyltransferase family genes (UGT2B15 and UGT2B17) in glucuronidation-competent cells and excreted, but not in glucuronidation-deficient cells. Thus, low glucuronidation activity enables prostate tumors to preserve androgens, which increases hormone treatment resistance and may be detectable by functional imaging. Methods: We knocked out (KO) UGT2B15 and 17 in LNCaP cells and tested the DHT retention rate in the cell lines by pulse-chase using [3H]DHT as a probe. Free and DHT-G retention rates were separately determined after 5 to 60 min. To increase the signal difference between control and KO cells, we screened several ATP-binding cassette transporter inhibitors to block DHT-G excretion. We performed [18F]DHT PET/CT in castrated mice having a control and a KO xenograft on contralateral flanks ( n = 3). The ratio of the standard uptake value (SUV) in control to KO xenografts in each mouse was calculated. To increase the ratio between control and KO tumors, 50µg cyclosporin A (CSA) was injected 30 min before injecting [18F]DHT. Results: After 5 minutes of chase, control cells retained twice the DHT of KO cells. In control cells, 50%-70% DHT was glucuronidated. Almost no DHT-G was detected in KO cells, and free DHT was similar to control. Of the inhibitors, only CSA increased DHT-G (but not free DHT) in control cells, resulting in a 3-4-fold increase in overall signal. In vivo PET/CT showed control xenografts had higher peak SUV but also a higher elution rate. CSA increased the SUV ratio by 1.5-2. Conclusions: We developed a PET/CT modality to detect androgen inactivation in a prostate cancer xenograft model. Androgen-glucuronidation-proficient tumors give off a stronger signal that is increased by ATP transporter inhibition. Our method can provide a noninvasive means of determining androgen metabolism status and therefore could possibly predict effectiveness of potential therapies in a subgroup of tumors predisposed to androgen deprivation resistance.

scholarly journals Preclinical Evaluation of 89Zr-Df-IAB22M2C PET as an Imaging Biomarker for the Development of the GUCY2C-CD3 Bispecific PF-07062119 as a T Cell Engaging Therapy

2021 ◽  
Author(s):  
Kevin P. Maresca ◽  
Jianqing Chen ◽  
Divya Mathur ◽  
Anand Giddabasappa ◽  
Adam Root ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Ex Vivo ◽  
Standard Uptake Value ◽  
Imaging Biomarker ◽  
Distribution Analysis ◽  
T Cell Infiltration ◽  
Positron Emission

Abstract Purpose A sensitive and specific imaging biomarker to monitor immune activation and quantify pharmacodynamic responses would be useful for development of immunomodulating anti-cancer agents. PF-07062119 is a T cell engaging bispecific antibody that binds to CD3 and guanylyl cyclase C, a protein that is over-expressed by colorectal cancers. Here, we used 89Zr-Df-IAB22M2C (89Zr-Df-Crefmirlimab), a human CD8-specific minibody to monitor CD8+ T cell infiltration into tumors by positron emission tomography. We investigated the ability of 89Zr-Df-IAB22M2C to track anti-tumor activity induced by PF-07062119 in a human CRC adoptive transfer mouse model (with injected activated/expanded human T cells), as well as the correlation of tumor radiotracer uptake with CD8+ immunohistochemical staining. Procedures NOD SCID gamma mice bearing human CRC LS1034 tumors were treated with four different doses of PF-07062119, or a non-targeted CD3 BsAb control, and imaged with 89Zr-Df-IAB22M2C PET at days 4 and 9. Following PET/CT imaging, mice were euthanized and dissected for ex vivo distribution analysis of 89Zr-Df-IAB22M2C in tissues on days 4 and 9, with additional data collected on day 6 (supplementary). Data were analyzed and reported as standard uptake value and %ID/g for in vivo imaging and ex vivo tissue distribution. In addition, tumor tissues were evaluated by immunohistochemistry for CD8+ T cells. Results The results demonstrated substantial mean uptake of 89Zr-Df-IAB22M2C (%ID/g) in PF-07062119-treated tumors, with significant increases in comparison to non-targeted BsAb-treated controls, as well as PF-07062119 dose-dependent responses over time of treatment. A moderate correlation was observed between tumor tissue radioactivity uptake and CD8+ cell density, demonstrating the value of the imaging agent for non-invasive assessment of intra-tumoral CD8+ T cells and the mechanism of action for PF-07062119. Conclusion Immune-imaging technologies for quantitative cellular measures would be a valuable biomarker in immunotherapeutic clinical development. We demonstrated a qualification of 89Zr-IAB22M2C PET to evaluate PD responses (mice) to a novel immunotherapeutic.

Abstract 530: In vivo DVT Inflammation Presages Vein Wall Injury, and is Ameliorated by Statin Therapy

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Chase W Kessinger ◽  
Guanming Qi ◽  
Ahmed Tawakol ◽  
Peter K Henke ◽  
Farouc A Jaffer
Keyword(s):  
Statin Therapy ◽  
Fdg Pet ◽  
Ex Vivo ◽  
Vena Cava ◽  
Standard Uptake Value ◽  
Vein Wall ◽  
Positron Emission ◽  
Pet Ct ◽  
Fdg Pet Ct

Objective: Inflammation mediates early venous thrombosis (VT) resolution and can induce vein wall scarring (VWS), a key driver of the morbid post-thrombotic syndrome (PTS). Statins exhibit anti-inflammatory properties, and may positively impact VWS after VT. However, whether early inflammation contributes to this process and can be detected is not known. In this study, we hypothesized that early VT inflammation detected by 18F-fludeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) could predict subsequent VWS and that both VT inflammation and VWS would be attenuated by statin therapy. Methods: Stasis VT was induced by complete ligation in male C57BL/6J mice (n=55) in either the infrarenal inferior vena cava (IVC, n=42) or right jugular vein (n=13). IVC VT mice were randomized to statin or control groups. Statin (rosuvastatin 5mg/kg) was given by oral gavage starting one day prior to VT induction; control mice received PBS. All mice underwent survival FDG-PET/CT venography imaging on day 2. FDG-PET inflammation signals (standard uptake value (SUV), SUVmax, target-to-background ratios (TBR)) were measured. Picrosirius red staining of day 14 VT sections measured vein wall collagen/thickness. Ex vivo VT tissue gamma counting of a subgroup was performed at day 2. Whole-thrombus protein/mRNA and VT tissue sections assessed neutrophil content. Results: FDG-PET/CT at day 2 revealed increased FDG uptake in jugular VT over the contralateral sham surgery vein (p<0.001). Statin-treated mice showed a decrease in FDG-PET SUV, SUVmax and TBR (p<0.05 for all). Whole-thrombus analyses and tissue section immunostaining showed reduced thrombus neutrophil content at day 2, without reducing GLUT1 or MPO expression (p>0.05). At day 14, statin therapy significantly reduced VWS (p=0.02). In mice undergoing survival imaging, the day 2 FDG-PET VT inflammation signal correlated significantly with the magnitude of day 14 VWS (IVC VT r=0.74, p<0.001) and jugular models of VT (r=0.62, p=0.02). Conclusions: Quantitative FDG inflammation imaging demonstrates that early VT inflammation presages subsequent VWS, and is ameliorated by prophylactic statin therapy. The overall findings support the concept that statins and could reduce VWS and PTS.

scholarly journals Improved Quantification of 18F-FDG PET during 131I-Rituximab Therapy on Mouse Lymphoma Models after 131I Prompt Emission Correction

Diagnostics ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 144
Author(s):  
Lee ◽  
Kim ◽  
Kim
Keyword(s):  
Mouse Model ◽  
Fdg Pet ◽  
Standard Uptake Value ◽  
Correction Method ◽  
Positron Emission ◽  
Emission Effect ◽  
18F Fdg ◽  
The Difference ◽  
Prompt Emission

18F-FDG Positron Emission Tomography (PET) is used to monitor tumor response to 131I-therapy, but is confounded by prompt emissions (284, 364, 637, and 723 keV) from 131I, particularly in animal PET imaging. We propose a method for correcting this emission in 18F-FDG PET. The 131I prompt emission effect was assessed within various energy windows and various activities. We applied a single gamma correction method to a phantom and in vivo mouse model. The 131I prompt emission fraction was 12% when 300 µCi of 131I and 100 µCi of FDG were administered, and increased exponentially with escalating 131I activity for all energy windows. The difference in spill-over ratio was reduced to <5% after 131I prompt emission correction. In the mouse model, the standard uptake value (SUV) did not differ significantly between FDG PET only (gold standard) and FDG PET after 131I prompt emission-correction, whereas it was overestimated by 38% before correction. Contrast was improved by 18% after 131I prompt emission correction. We first found that count contamination on 18F-FDG follow-up scans due to 131I spilled-over count after 131I rituximab tumor targeted therapy. Our developed 131I prompt emission-correction method increased accuracy during measurement of standard uptake values on 18F-FDG PET.

scholarly journals Integrated 18F-T807 Tau PET, Structural MRI, and Plasma Tau in Tauopathy Neurodegenerative Disorders

2021 ◽  
Vol 13 ◽  
Author(s):  
Cheng-Hsuan Li ◽  
Ta-Fu Chen ◽  
Ming-Jang Chiu ◽  
Ruoh-Fang Yen ◽  
Ming-Chieh Shih ◽  
...  
Keyword(s):  
Brain Mri ◽  
Standard Uptake Value ◽  
Structural Mri ◽  
Tracer Uptake ◽  
Cortical Atrophy ◽  
Clinical Assessments ◽  
Positron Emission ◽  
Tau Pet ◽  
And Control

Background and Objective: Tau-specific positron emission topography (PET) imaging enables in vivo assessment of Alzheimer's disease (AD). We aimed to investigate its performance in combination with plasma tau levels in patients with non-AD tauopathy.Methods: A total of 47 participants were enrolled, including 10 healthy controls, 16 with tauopathy parkinsonism syndromes (9 with corticobasal syndrome [CBS], 7 with progressive supranuclear palsy [PSP]), 9 with frontotemporal dementia (FTD), 4 with AD, and 8 with Parkinson's disease (PD). All participants underwent clinical assessments, 18F-T807 tau PET, brain MRI, and plasma tau assay.Results: The global cortical standard uptake value ratio (SUVR) of 18F-T807 PET was comparable between PD and control (p = 0.088). The cortical SUVR was significantly higher in AD group (p = 0.002) but was modestly increased in PSP group compared to the PD group (p = 0.044), especially in parietal and pallidal regions. Asymmetric 18F-T807 uptake at the pallidum was noted in patients with CBS and FTD. Cortical tau tracer uptake was associated with increased plasma total tau level (p = 0.016), especially in frontal and parietal regions. Regional tracer uptake was correlated with cortical thinning in patients with CBS and PSP (CBS: r = −0.092, p = 0.025; PSP: r = −0.114, p = 0.015).Conclusions: The 18F-T807 tau tracer uptake was only modestly increased in patients with PSP. Although the cortical tau tracer uptake correlated with regional cortical atrophy and plasma tau levels, a four-repeated tau-specific tracer is needed for future classifying tauopathy parkinsonism syndromes.

Functional characterization of human brown adipose tissue metabolism

2020 ◽  
Vol 477 (7) ◽  
pp. 1261-1286 ◽  
Author(s):  
Marie Anne Richard ◽  
Hannah Pallubinsky ◽  
Denis P. Blondin
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Functional Characterization ◽  
Human Infants ◽  
Positron Emission ◽  
Brown Adipose ◽  
Treatment Of Obesity ◽  
And Function

Brown adipose tissue (BAT) has long been described according to its histological features as a multilocular, lipid-containing tissue, light brown in color, that is also responsive to the cold and found especially in hibernating mammals and human infants. Its presence in both hibernators and human infants, combined with its function as a heat-generating organ, raised many questions about its role in humans. Early characterizations of the tissue in humans focused on its progressive atrophy with age and its apparent importance for cold-exposed workers. However, the use of positron emission tomography (PET) with the glucose tracer [18F]fluorodeoxyglucose ([18F]FDG) made it possible to begin characterizing the possible function of BAT in adult humans, and whether it could play a role in the prevention or treatment of obesity and type 2 diabetes (T2D). This review focuses on the in vivo functional characterization of human BAT, the methodological approaches applied to examine these features and addresses critical gaps that remain in moving the field forward. Specifically, we describe the anatomical and biomolecular features of human BAT, the modalities and applications of non-invasive tools such as PET and magnetic resonance imaging coupled with spectroscopy (MRI/MRS) to study BAT morphology and function in vivo, and finally describe the functional characteristics of human BAT that have only been possible through the development and application of such tools.

18F-Deoxyglucose PET for the staging of oesophageal cancer

2003 ◽  
Vol 42 (03) ◽  
pp. 90-93 ◽  
Author(s):  
N. Döbert ◽  
O. Rieker ◽  
W. Kneist ◽  
St. Mose ◽  
A. Teising ◽  
...  
Keyword(s):  
Oesophageal Cancer ◽  
Squamous Cell ◽  
Distal Part ◽  
Standard Uptake Value ◽  
Squamous Cell Carcinomas ◽  
Tumour Grading ◽  
Positron Emission ◽  
Group A ◽  
The Mean ◽  
Drop Outs

SummaryAim: Evaluation of the influence of histopathologic sub-types and grading of primaries of oesophageal cancer, relative to their size and location, on the uptake of 18F-deoxyglucose (FDG) as measured by positron emission tomography (PET). Methods: 50 consecutive patients were evaluated. There were four drop-outs due to previous surgical and/or chemotherapeutical treatments and thus in 46 patients (28 squamous cell carcinomas and 18 adenocarcinomas) a pretherapeutic PET evalution of the primary including a standard uptake value (SUV) was obtained. In 42 cases data on tumour grading were available also. Results: Squamous cell carcinomas (SCC) were in 7/13/8 cases located in the proximal, medial and distal part of the oesophagus, respectively the grading was Gx in 3, G 2 in 12, G2-3 in 7, and G3 in 6 cases. The SUVmax showed a mean of 6.5 ± 2.8 (range 1.7-13.5). Adenocarcinomas (ACA) were located in the medial oesophagus in two cases and otherwise in its distal parts. Grading was Gx in one, G2 in 4, G2-3 in 3, G3 in 3, G3-4 in 3, and G4 in one case. The mean SUVmax was 5.2 ± 3.2 (range 1-13.6) and this was not significantly different from the SCC. Concerning the tumour grading there was a slight, statistically not relevant trend towards higher SUVmax in more dedifferentiated cancer. Discussion: SCC and ACA of the oesophagus show no relevant differences in the FDG-uptake. While there was a significant variability of tumour uptake in the overall study group, a correlation of SUV and tumour grading was not found.

Plasminogen Activation In Vivo upon Intravenous Infusion of DDAVP

1992 ◽  
Vol 67 (01) ◽  
pp. 111-116 ◽  
Author(s):  
Marcel Levi ◽  
Jan Paul de Boer ◽  
Dorina Roem ◽  
Jan Wouter ten Cate ◽  
C Erik Hack
Keyword(s):  
Monoclonal Antibodies ◽  
Plasminogen Activator ◽  
Plasma Levels ◽  
Fold Increase ◽  
Fibrinolytic System ◽  
Plasminogen Activation ◽  
Plasminogen Activator Activity ◽  
Insight Into

SummaryInfusion of desamino-d-arginine vasopressin (DDAVP) results in an increase in plasma plasminogen activator activity. Whether this increase results in the generation of plasmin in vivo has never been established.A novel sensitive radioimmunoassay (RIA) for the measurement of the complex between plasmin and its main inhibitor α2 antiplasmin (PAP complex) was developed using monoclonal antibodies preferentially reacting with complexed and inactivated α2-antiplasmin and monoclonal antibodies against plasmin. The assay was validated in healthy volunteers and in patients with an activated fibrinolytic system.Infusion of DDAVP in a randomized placebo controlled crossover study resulted in all volunteers in a 6.6-fold increase in PAP complex, which was maximal between 15 and 30 min after the start of the infusion. Hereafter, plasma levels of PAP complex decreased with an apparent half-life of disappearance of about 120 min. Infusion of DDAVP did not induce generation of thrombin, as measured by plasma levels of prothrombin fragment F1+2 and thrombin-antithrombin III (TAT) complex.We conclude that the increase in plasminogen activator activity upon the infusion of DDAVP results in the in vivo generation of plasmin, in the absence of coagulation activation. Studying the DDAVP induced increase in PAP complex of patients with thromboembolic disease and a defective plasminogen activator response upon DDAVP may provide more insight into the role of the fibrinolytic system in the pathogenesis of thrombosis.

Sign in / Sign up

Export Citation Format

Share Document