scholarly journals PET Imaging of CD8 via SMART for Monitoring the Immunotherapy Response

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Lingyi Sun ◽  
Zhonghan Li ◽  
Yongyong Ma ◽  
Johannes Ludwig ◽  
Hyun S. Kim ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Positive Response ◽  
Imaging Study ◽  
Inadequate Response ◽  
Time Treatment ◽  
Promising Strategy ◽  
Positron Emission ◽  
First Time ◽  
Ct26 Tumor ◽  
Selection Of

Imaging of CD8 receptors on T-cells by positron emission tomography (PET) has been considered a promising strategy for monitoring the treatment response to immunotherapy. In this study, a trial of imaging CD8 with our newly developed sequential multiple-agent receptor targeting (SMART) technology was conducted. Mice bearing a subcutaneous colorectal CT26 tumor received three times different immunotherapy treatments (PD1 or CTLA4 or combined). On either day 7 or day 14 after the first time treatment, the PET imaging study was performed with sequentially administered TCO-modified anti-CD8 antibody and 64Cu-labeled MeTz-NOTA-RGD. However, no positive response was detected, probably due to (1) inappropriate selection of biomarkers for the SMART strategy, (2) limited TCO modification on the anti-CD8 antibody, and (3) inadequate response of the CT26 tumor to the selected immunotherapies. Therefore, the potential of applying SMART in imaging CD8 was not demonstrated in this study, and further optimization will be necessary before it can be applied in imaging CD8.

scholarly journals 11C- and 18F-Radiotracers for In Vivo Imaging of the Dopamine System: Past, Present and Future

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 108
Author(s):  
Michael R. Kilbourn
Keyword(s):  
Pet Imaging ◽  
In Vivo Imaging ◽  
Dopamine Synthesis ◽  
Dopamine System ◽  
Synaptic Release ◽  
Positron Emission ◽  
The Central Nervous System ◽  
Pet Radiotracers ◽  
Selection Of

The applications of positron emission tomography (PET) imaging to study brain biochemistry, and in particular the aspects of dopamine neurotransmission, have grown significantly over the 40 years since the first successful in vivo imaging studies in humans. In vivo PET imaging of dopaminergic functions of the central nervous system (CNS) including dopamine synthesis, vesicular storage, synaptic release and receptor binding, and reuptake processes, are now routinely used for studies in neurology, psychiatry, drug abuse and addiction, and drug development. Underlying these advances in PET imaging has been the development of the unique radiotracers labeled with positron-emitting radionuclides such as carbon-11 and fluorine-18. This review focuses on a selection of the more accepted and utilized PET radiotracers currently available, with a look at their past, present and future.

scholarly journals 2-[3,5-Bis-(2-fluorobenzylidene)-4-piperidon-1-yl]-N-(4-fluorobenzyl)-acetamide and Its Evaluation as an Anticancer Agent

2013 ◽  
Vol 2013 ◽  
pp. 1-9
Author(s):  
Pallavi Lagisetty ◽  
Hrushikesh Agashe ◽  
Vibhudutta Awasthi
Keyword(s):  
Pet Imaging ◽  
Anticancer Agent ◽  
Tumor Regression ◽  
Radiochemical Yield ◽  
Emission Tomography ◽  
Whole Body ◽  
Positron Emission ◽  
Proliferation Assays ◽  
First Time ◽  
Kinetics Of

Synthesis of 2-[3,5-bis-(2-fluorobenzylidene)-4-piperidon-1-yl]-N-(4-fluorobenzyl)-acetamide, a derivative of 3,5-bis-(2-fluorobenzylidene)-4-piperidone (EF24), as an antiproliferative and imageable compound is described. The radioactive derivative was synthesized in 40–45% radiochemical yield using N-[4-fluoro(18F)benzyl]-2-bromoacetamide (NFLOBA) as a radiolabeled synthon for coupling with EF24. Cell proliferation assays showed that 2-[3,5-bis-(2-fluorobenzylidene)-4-piperidon-1-yl]-N-(4-fluorobenzyl)-acetamide (NFLOBA-EF24) had antiproliferative efficacy similar to that of EF24 in lung adenocarcinoma H441 cells.18F-NFLOBA-EF24 was investigated in normal rats for whole-body PET imaging and biodistribution. At necropsy after 1 h of injection, about 12% of injected compound was still circulating in blood; liver, kidney, and muscle were other tissues with moderate amounts of accumulation. In order to assess the tumor-suppressive activity, nonradioactive NFLOBA-EF24 was administered in nude rats carrying xenograft H441 tumor. After 15 days of treatment, the tumor size decreased by approximately 83% compared to the tumors in control rats. The tumor regression was also confirmed by molecular imaging of glucose metabolism with18F- fluorodeoxyglucose. The results suggest that EF24 could be efficiently modified with18F-labeled synthon NFLOBA for convenient PET imaging without altering the antitumor efficacy of the original compound. This study provides visual kinetics of synthetic curcuminoid EF24 by positron emission tomography for the first time.

scholarly journals Integrin VLA-4 as a PET imaging biomarker of hyper-adhesion in transgenic sickle mice

2020 ◽  
Vol 4 (17) ◽  
pp. 4102-4112
Author(s):  
Lydia A. Perkins ◽  
Lea Nyiranshuti ◽  
Lynda Little-Ihrig ◽  
Joseph D. Latoche ◽  
Kathryn E. Day ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Imaging Biomarker ◽  
Noninvasive Method ◽  
Cell Disease ◽  
Pet Tracer ◽  
Positron Emission ◽  
Late Antigen ◽  
Radionuclide Tracer ◽  
First Time

Abstract In sickle cell disease (SCD), very late antigen-4 (VLA-4 or integrin α4β1) mediates the adhesion of reticulocytes to inflamed, proinflammatory endothelium, a key process in promoting vaso-occlusive episodes (VOEs). We hypothesized that a radionuclide tracer targeting VLA-4 could be harnessed as a positron emission tomography (PET) imaging biomarker of VOEs. We tested the VLA-4 peptidomimetic PET tracer 64Cu-CB-TE1A1P-PEG4-LLP2A (64Cu-LLP2A) for imaging hyper-adhesion–associated VOEs in the SCD Townes mouse model. With lipopolysaccharide (LPS)-induced VOEs, 64Cu-LLP2A uptake was increased in the bone marrow of the humeri and femurs, common sites of VOEs in SCD mice compared with non-SCD mice. Treatment with a proven inhibitor of VOEs (the anti-mouse anti-P-selectin monoclonal antibody [mAb] RB40.34) during LPS stimulation led to a reduction in the uptake of 64Cu-LLP2A in the humeri and femurs to baseline levels, implying blockade of VOE hyper-adhesion. Flow cytometry with Cy3-LLP2A demonstrated an increased percentage of VLA-4–positive reticulocytes in SCD vs non-SCD mice in the bone and peripheral blood after treatment with LPS, which was abrogated by anti-P-selectin mAb treatment. These data, for the first time, show in vivo imaging of VLA-4–mediated hyper-adhesion, primarily of SCD reticulocytes, during VOEs. PET imaging with 64Cu-LLP2A may serve as a valuable, noninvasive method for identifying sites of vaso-occlusion and may provide an objective biomarker of disease severity and anti-P-selectin treatment efficacy in patients with SCD.

scholarly journals Preserved caudate function in young-onset patients with Parkinson’s disease: a dual-tracer PET imaging study

2019 ◽  
Vol 12 ◽  
pp. 175628641985140
Author(s):  
Yu-jie Yang ◽  
Jing-jie Ge ◽  
Feng-tao Liu ◽  
Zhen-yang Liu ◽  
Jue Zhao ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Pet Imaging ◽  
Late Onset ◽  
Imaging Study ◽  
Young Onset ◽  
Metabolic Characteristics ◽  
Positron Emission ◽  
Similar Disease ◽  
Dual Tracer

Parkinson’s disease (PD) is a highly heterogeneous clinical entity. Patients with young-onset PD (YOPD) show some characteristic manifestations to late-onset PD (LOPD). The current study aimed to investigate the cerebral dopaminergic and metabolic characteristics in YOPD with positron emission tomography (PET) imaging. In our study, 103 subjects (42 YOPD and 61 LOPD patients) accepted both 11C-N-2-carbomethoxy-3-(4-fluorophenyl)-tropane (11C-CFT) and 18F-fluorodeoxyglucose (18F-FDG) cerebral PET imaging. Sixty-two patients out of 103 patients in our study completed the cognition tests. In this limited subsection, YOPD patients performed better in cognitive functioning than LOPD patients of similar disease duration. In 11C-CFT imaging, dopamine transporter binding in caudate was relatively spared in YOPD compared with lesions in putamen. In 18F-FDG PET, YOPD patients showed increased metabolism in basal ganglia relative to the healthy controls. When compared with LOPD patients, YOPD patients exhibited hypermetabolism in caudate and hypometabolism in putamen. Furthermore, the regional metabolic values in caudate correlated positively and moderately with the dopaminergic binding deficiency in caudate. The findings of this imaging study might offer new perspectives in understanding the characteristic manifestations in YOPD in light of better-preserved cognition function.

scholarly journals Preliminary Evaluations of [11C]Verubulin: Implications for Microtubule Imaging With PET

2021 ◽  
Vol 15 ◽  
Author(s):  
Anton Lindberg ◽  
Andrew V. Mossine ◽  
Arturo Aliaga ◽  
Robert Hopewell ◽  
Gassan Massarweh ◽  
...  
Keyword(s):  
Rat Brain ◽  
Pet Imaging ◽  
Imaging Study ◽  
Positron Emission ◽  
Human Use ◽  
Pretreatment Conditions ◽  
Human Primate

[11C]Verubulin (a.k.a.[11C]MCP-6827), [11C]HD-800 and [11C]colchicine have been developed for imaging microtubules (MTs) with positron emission tomography (PET). The objective of this work was to conduct an in vivo comparison of [11C]verubulin for MT imaging in mouse and rat brain, as well as an in vitro study with this radiotracer in rodent and human Alzheimer’s Disease tissue. Our preliminary PET imaging studies of [11C]verubulin in rodents revealed contradictory results between mouse and rat brain uptake under pretreatment conditions. In vitro autoradiography with [11C]verubulin showed an unexpected higher uptake in AD patient tissue compared with healthy controls. We also conducted the first comparative in vivo PET imaging study with [11C]verubulin, [11C]HD-800 and [11C]colchicine in a non-human primate. [11C]Verubulin and [11C]HD-800 require pharmacokinetic modeling and quantification studies to understand the role of how these radiotracers bind to MTs before translation to human use.

A quantitative LC–MS/MS approach for monitoring 2′-fluoro-2′-deoxy-D-glucose uptake in tumor tissue

Bioanalysis ◽  
2021 ◽  
Author(s):  
Wenlin Li ◽  
Cathy Zhang ◽  
Nanni Huser ◽  
Chad Ray ◽  
Scott Fountain ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Fdg Pet ◽  
Tumor Model ◽  
Cost Effective ◽  
Mouse Tumor ◽  
Internal Standards ◽  
Positron Emission ◽  
Imaging Results ◽  
Noninvasive Biomarker ◽  
Selection Of

Purpose: Develop a quantitative LC–MS/MS method for FDG, FDG-monophosphate, glucose and glucose-monophosphate in mouse tumor models to assist in validating the use of [18F]FDG-positron emission tomography (PET) imaging for anticancer therapies in a clinical setting. Methodology/results: Analytes were isolated from tumors by protein precipitation and detected on a Sciex API-5500 mass spectrometer. Improved assay robustness and selectivity were achieved through chromatographic separation of FDG-monophosphate from glucose-monophosphate, selection of a unique ion transition and incorporation of stable isotope labeled internal standards. In a mouse JIMT-1 tumor model, FDG-monophosphate levels measured by LC–MS/MS correlated with [18F]FDG-PET imaging results. Conclusion: LC–MS/MS analysis of FDG-monophosphate accumulation in tumors is a cost-effective tool to gauge the translational potential of [18F]FDG-PET imaging as a noninvasive biomarker in clinical studies.

scholarly journals Validation of SV2A-Targeted PET Imaging for Noninvasive Assessment of Neuroendocrine Differentiation in Prostate Cancer

2021 ◽  
Vol 22 (23) ◽  
pp. 13085
Author(s):  
Bing Guan ◽  
Ning Zhou ◽  
Cheng-Yang Wu ◽  
Songye Li ◽  
Yu-An Chen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Pet Imaging ◽  
Neuroendocrine Differentiation ◽  
Imaging Study ◽  
Clinical Samples ◽  
Diagnostic Challenge ◽  
Imaging Evaluation ◽  
Protein Levels ◽  
Positron Emission ◽  
Noninvasive Assessment

Neuroendocrine prostate cancer (NEPC) is an aggressive and lethal variant of prostate cancer (PCa), and it remains a diagnostic challenge. Herein we report our findings of using synaptic vesicle glycoprotein 2 isoform A (SV2A) as a promising marker for positron emission tomography (PET) imaging of neuroendocrine differentiation (NED). The bioinformatic analyses revealed an amplified SV2A gene expression in clinical samples of NEPC versus castration-resistant PCa with adenocarcinoma characteristics (CRPC-Adeno). Importantly, significantly upregulated SV2A protein levels were found in both NEPC cell lines and tumor tissues. PET imaging studies were carried out in NEPC xenograft models with 18F-SynVesT-1. Although 18F-SynVesT-1 is not a cancer imaging agent, it showed a significant uptake level in the SV2A+ tumor (NCI-H660: 0.70 ± 0.14 %ID/g at 50–60 min p.i.). The SV2A blockade resulted in a significant reduction of tumor uptake (0.25 ± 0.03 %ID/g, p = 0.025), indicating the desired SV2A imaging specificity. Moreover, the comparative PET imaging study showed that the DU145 tumors could be clearly visualized by 18F-SynVesT-1 but not 68Ga-PSMA-11 nor 68Ga-DOTATATE, further validating the role of SV2A-targeted imaging for noninvasive assessment of NED in PCa. In conclusion, we demonstrated that SV2A, highly expressed in NEPC, can serve as a promising target for noninvasive imaging evaluation of NED.

Alterations in regional decreased cerebral blood flow in patients with irritable bowel syndrome-A PET imaging study

2001 ◽  
Vol 120 (5) ◽  
pp. A637-A637
Author(s):  
Y RINGEL ◽  
D DROSSMAN ◽  
T TURKINGTON ◽  
B BRADSHAW ◽  
R COLEMAN ◽  
...  
Keyword(s):  
Blood Flow ◽  
Irritable Bowel Syndrome ◽  
Cerebral Blood Flow ◽  
Pet Imaging ◽  
Imaging Study ◽  
Irritable Bowel

Competition of Verb Aspects and Its Resolution as a Creative Act (Based on the Material of Aspects Variants in the Texts by F. M. Dostoevsky)

2020 ◽  
Vol 81 (2) ◽  
pp. 56-63
Author(s):  
S. A. Karpukhin
Keyword(s):  
Traditional Method ◽  
Contextual Analysis ◽  
Verb Aspect ◽  
Component Theory ◽  
Two Component ◽  
Artistic Interpretation ◽  
New Perspective ◽  
First Time ◽  
Selection Of ◽  
Aspectual Meaning

The article considers the competition of verbal aspects from a new perspective. Instead of employing the traditional method of demonstrating this phenomenon — an empirical replacement of the aspect of a verb in a phrase with the opposite — the author examines Dostoevsky’s choice between the variants found in different manuscripts of the same text. For the first time, based on a two-component theory of the semantic invariant of a verb type, the aspectual meaning of the selection of a verb aspect is revealed and, as a result of contextual analysis, an artistic interpretation of the selected type is proposed.

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