scholarly journals In Vivo 6-([18F]Fluoroacetamido)-1-hexanoicanilide PET Imaging of Altered Histone Deacetylase Activity in Chemotherapy-Induced Neurotoxicity

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Nobuyoshi Fukumitsu ◽  
Skye Hsin-Hsien Yeh ◽  
Leo Garcia Flores II ◽  
Uday Mukhopadhyay ◽  
Daniel Young ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Histone Deacetylases ◽  
Histone Deacetylation ◽  
Antitumor Effects ◽  
Neuroprotective Effects ◽  
Positron Emission ◽  
Group A ◽  
Expression Activity ◽  
Group B

Background. Histone deacetylases (HDACs) regulate gene expression by changing histone deacetylation status. Neurotoxicity is one of the major side effects of cisplatin, which reacts with deoxyribonucleic acid (DNA) and has excellent antitumor effects. Suberoylanilide hydroxamic acid (SAHA) is an HDAC inhibitor with neuroprotective effects against cisplatin-induced neurotoxicity. Purpose. We investigated how cisplatin with and without SAHA pretreatment affects HDAC expression/activity in the brain by using 6-([18F]fluoroacetamido)-1-hexanoicanilide ([18F]FAHA) as a positron emission tomography (PET) imaging agent for HDAC IIa. Materials and Methods. [18F]FAHA and [18F]fluoro-2-deoxy-2-D-glucose ([18F]FDG) PET studies were done in 24 mice on 2 consecutive days and again 1 week later. The mice were divided into three groups according to drug administration between the first and second imaging sessions (Group A: cisplatin 2 mg/kg, twice; Group B: cisplatin 4 mg/kg, twice; Group C: cisplatin 4 mg/kg, twice, and SAHA 300 mg/kg pretreatment, 4 times). Results. The Ki value of [18F]FAHA was increased and the percentage of injected dose/tissue g (% ID/g) of [18F]FDG was decreased in the brains of animals in Groups A and B. The Ki value of [18F]FAHA and % ID/g of [18F]FDG were not significantly different in Group C. Conclusions. [18F]FAHA PET clearly showed increased HDAC activity suggestive of cisplatin neurotoxicity in vivo, which was blocked by SAHA pretreatment.

Cruciferous Vegetables as Antioxidative, Chemopreventive and Antineoplasic Functional Foods: Preclinical and Clinical Evidences of Sulforaphane Against Prostate Cancers

2019 ◽  
Vol 24 (40) ◽  
pp. 4779-4793 ◽  
Author(s):  
Paulo M.P. Ferreira ◽  
Lays A.R.L. Rodrigues ◽  
Lunna Paula de Alencar Carnib ◽  
Paulo Víctor de Lima Sousa ◽  
Luis Michel Nolasco Lugo ◽  
...  
Keyword(s):  
Histone Deacetylases ◽  
Cruciferous Vegetables ◽  
Tumor Cell Death ◽  
Antitumor Effects ◽  
Antiapoptotic Proteins ◽  
Cycle Arrest ◽  
Government Documents ◽  
Prostate Cancers

Background: Sulforaphane (SF, 1-isothiocyanato-4-(methyl-sulfinyl)-butane) is found in broccoli, cabbage and cauliflower. Methods: we performed a critical review on the antioxidative, chemopreventive and antitumor effects of SF from cruciferous vegetables against prostate cancers and molecular pathways. For a complete and reliable review, primary and secondary resources were used, including original and review articles, books and government documents published until March 2018. Articles that are in duplicity and disconnected are not considered for review. SF is derived from glucoraphanin (4-methyl-sulfinyl-butyl-glucosinate), being one of the most commonly found isothiocyanates in vegetables from Brassica spp., especially in broccoli samples. In vitro studies indicate that SF induces apoptosis in a dependent or non-dependent method of androgens by transcription of tumor suppressor genes, oxidation response and higher expression of phase II enzymes in prostate cancer cells. Sulforaphane also decreases transcription of the nuclear factor kB and antiapoptotic proteins, expression of cyclin D2 and survivin and DNA synthesis, increases Nrf2 gene activity, interferes with genome compacting by inhibition of histone deacetylases and disrupts Hsp90 complexes, which cause cell cycle arrest, mitosis interruption, activation of caspases and mitochondria depolarization. Conclusion: SF and cruciferous vegetables play antioxidative and chemopreventive role, delaying or blocking in vivo carcinogenesis, causing biochemical and epigenetic changes, preventing, delaying, or reversing preneoplastic or advanced prostate lesions, and frequently activating tumor cell death by intrinsic methods of apoptosis. These outcomes encourage the consumption of Brassica specimens, which could be easily achieved by the incorporation of food and vegetables rich in cruciferous isothiocyanates in the diet.

scholarly journals Development of a blood sample detector for multi-tracer positron emission tomography using gamma spectroscopy

2019 ◽  
Vol 6 (1) ◽  
Author(s):  
Carlos Velasco ◽  
Adriana Mota-Cobián ◽  
Jesús Mateo ◽  
Samuel España
Keyword(s):  
Positron Emission Tomography ◽  
Blood Sample ◽  
Pet Imaging ◽  
Spectroscopic Analysis ◽  
Gamma Spectroscopy ◽  
Emission Tomography ◽  
Blood Samples ◽  
Positron Emission

Abstract Background Multi-tracer positron emission tomography (PET) imaging can be accomplished by applying multi-tracer compartment modeling. Recently, a method has been proposed in which the arterial input functions (AIFs) of the multi-tracer PET scan are explicitly derived. For that purpose, a gamma spectroscopic analysis is performed on blood samples manually withdrawn from the patient when at least one of the co-injected tracers is based on a non-pure positron emitter. Alternatively, these blood samples required for the spectroscopic analysis may be obtained and analyzed on site by an automated detection device, thus minimizing analysis time and radiation exposure of the operating personnel. In this work, a new automated blood sample detector based on silicon photomultipliers (SiPMs) for single- and multi-tracer PET imaging is presented, characterized, and tested in vitro and in vivo. Results The detector presented in this work stores and analyzes on-the-fly single and coincidence detected events. A sensitivity of 22.6 cps/(kBq/mL) and 1.7 cps/(kBq/mL) was obtained for single and coincidence events respectively. An energy resolution of 35% full-width-half-maximum (FWHM) at 511 keV and a minimum detectable activity of 0.30 ± 0.08 kBq/mL in single mode were obtained. The in vivo AIFs obtained with the detector show an excellent Pearson’s correlation (r = 0.996, p < 0.0001) with the ones obtained from well counter analysis of discrete blood samples. Moreover, in vitro experiments demonstrate the capability of the detector to apply the gamma spectroscopic analysis on a mixture of 68Ga and 18F and separate the individual signal emitted from each one. Conclusions Characterization and in vivo evaluation under realistic experimental conditions showed that the detector proposed in this work offers excellent sensibility and stability. The device also showed to successfully separate individual signals emitted from a mixture of radioisotopes. Therefore, the blood sample detector presented in this study allows fully automatic AIFs measurements during single- and multi-tracer PET studies.

scholarly journals Metabolic radiolabeling and in vivo PET imaging of cytotoxic T lymphocytes to guide combination adoptive cell transfer cancer therapy

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Dehua Lu ◽  
Yanpu Wang ◽  
Ting Zhang ◽  
Feng Wang ◽  
Kui Li ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Solid Tumors ◽  
Cytotoxic T Lymphocytes ◽  
Pet Imaging ◽  
Stage Migration ◽  
Cell Transfer ◽  
Tumor Infiltration ◽  
Antitumor Effects

Abstract Background Adoptive T cell transfer-based immunotherapy yields unsatisfactory results in the treatment of solid tumors, partially owing to limited tumor infiltration and the immunosuppressive microenvironment in solid tumors. Therefore, strategies for the noninvasive tracking of adoptive T cells are critical for monitoring tumor infiltration and for guiding the development of novel combination therapies. Methods We developed a radiolabeling method for cytotoxic T lymphocytes (CTLs) that comprises metabolically labeling the cell surface glycans with azidosugars and then covalently conjugating them with 64Cu-1,4,7-triazacyclononanetriacetic acid-dibenzo-cyclooctyne (64Cu-NOTA-DBCO) using bioorthogonal chemistry. 64Cu-labeled control-CTLs and ovalbumin-specific CTLs (OVA-CTLs) were tracked using positron emission tomography (PET) in B16-OVA tumor-bearing mice. We also investigated the effects of focal adhesion kinase (FAK) inhibition on the antitumor efficacy of OVA-CTLs using a poly(lactic-co-glycolic) acid (PLGA)-encapsulated nanodrug (PLGA-FAKi). Results CTLs can be stably radiolabeled with 64Cu with a minimal effect on cell viability. PET imaging of 64Cu-OVA-CTLs enables noninvasive mapping of their in vivo behavior. Moreover, 64Cu-OVA-CTLs PET imaging revealed that PLGA-FAKi induced a significant increase in OVA-CTL infiltration into tumors, suggesting the potential for a combined therapy comprising OVA-CTLs and PLGA-FAKi. Further combination therapy studies confirmed that the PLGA-FAKi nanodrug markedly improved the antitumor effects of adoptive OVA-CTLs transfer by multiple mechanisms. Conclusion These findings demonstrated that metabolic radiolabeling followed by PET imaging can be used to sensitively profile the early-stage migration and tumor-targeting efficiency of adoptive T cells in vivo. This strategy presents opportunities for predicting the efficacy of cell-based adoptive therapies and for guiding combination regimens. Graphic Abstract

scholarly journals Novel 64Cu-Labeled CUDC-101 for in Vivo PET Imaging of Histone Deacetylases

2013 ◽  
Vol 4 (9) ◽  
pp. 858-862 ◽  
Author(s):  
Qingqing Meng ◽  
Feng Li ◽  
Sheng Jiang ◽  
Zheng Li
Keyword(s):  
Pet Imaging ◽  
Histone Deacetylases

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.

Training-induced alterations of the in vivo force-velocity relationship of human muscle

1981 ◽  
Vol 51 (3) ◽  
pp. 750-754 ◽  
Author(s):  
V. J. Caiozzo ◽  
J. J. Perrine ◽  
V. R. Edgerton
Keyword(s):  
Training Group ◽  
Knee Extension ◽  
Knee Extensors ◽  
Velocity Relationship ◽  
Slow Velocity ◽  
Group A ◽  
Force Velocity ◽  
Group B ◽  
Relationship Of

Seventeen male and female subjects (ages 20–38 yr) were tested pre- and posttraining for maximal knee extension torque at seven specific velocities (0, 0.84, 1.68, 2.51, 3.35, 4.19, and 5.03 rad . s-1) with an isokinetic dynamometer. Maximal knee extension torques were recorded at a specific joint angle (0.52 rad below the horizontal plane) for all test speeds. Subjects were randomly assigned to one of three experimental groups: group A, control, n = 7; group B, training at 1.68 rad . s-1, n = 5; or group C, training at 4.19 rad . s-1, n = 5. Subjects trained the knee extensors by performing two sets of 10 single maximal voluntary efforts three times a week for 4 wk. Before training, each training group exhibited a leveling-off of muscular tension in the slow velocity-high force region of the in vivo force-velocity relationship. Training at 1.68 rad . s-1 resulted in significant (P less than 0.05) improvements at all velocities except for 5.03 rad . s-1 and markedly affected the leveling-off in the slow velocity-high force region. Training at 4.19 rad . s-1 did not affect the leveling-off phenomenon but brought about significant improvements (P less than 0.05) at velocities of 2.51, 3.35, and 4.19 rad . s-1. The changes seen in the leveling-off phenomenon suggest that training at 1.68 rad . s-1 might have brought about an enhancement of motoneuron activation.

scholarly journals Photopolymerizable Injectable Cartilage Mimetic Hydrogel for the Treatment of Focal Chondral Lesions: A Proof of Concept Study in a Rabbit Animal Model

2018 ◽  
Vol 47 (1) ◽  
pp. 212-221 ◽  
Author(s):  
Cecilia Pascual-Garrido ◽  
Elizabeth A. Aisenbrey ◽  
Francisco Rodriguez-Fontan ◽  
Karin A. Payne ◽  
Stephanie J. Bryant ◽  
...  
Keyword(s):  
Animal Model ◽  
Chondrogenic Differentiation ◽  
Osteochondral Lesions ◽  
Chondral Defect ◽  
Group A ◽  
Group B ◽  
Safranin O

Background: In this study, we investigate the in vitro and in vivo chondrogenic capacity of a novel photopolymerizable cartilage mimetic hydrogel, enhanced with extracellular matrix analogs, for cartilage regeneration. Purpose: To (1) determine whether mesenchymal stem cells (MSCs) embedded in a novel cartilage mimetic hydrogel support in vitro chondrogenesis, (2) demonstrate that the proposed hydrogel can be delivered in situ in a critical chondral defect in a rabbit model, and (3) determine whether the hydrogel with or without MSCs supports in vivo chondrogenesis in a critical chondral defect. Study Design: Controlled laboratory study. Methods: Rabbit bone marrow–derived MSCs were isolated, expanded, encapsulated in the hydrogel, and cultured in chondrogenic differentiation medium for 9 weeks. Compressive modulus was evaluated at day 1 and at weeks 3, 6, and 9. Chondrogenic differentiation was investigated via quantitative polymerase reaction, safranin-O staining, and immunofluorescence. In vivo, a 3 mm–wide × 2-mm-deep chondral defect was created bilaterally on the knee trochlea of 10 rabbits. Each animal had 1 defect randomly assigned to be treated with hydrogel with or without MSCs, and the contralateral knee was left untreated. Hence, each rabbit served as its own matched control. Three groups were established: group A, hydrogel (n = 5); group B, hydrogel with MSCs (n = 5); and group C, control (n = 10). Repair tissue was evaluated at 6 months after intervention. Results: In vitro, chondrogenesis and the degradable behavior of the hydrogel by MSCs were confirmed. In vivo, the hydrogel could be delivered intraoperatively in a sterile manner. Overall, the hydrogel group had the highest scores on the modified O’Driscoll scoring system (group A, 17.4 ± 4.7; group B, 13 ± 3; group C, 16.7 ± 2.9) ( P = .11) and showed higher safranin-O staining (group A, 49.4% ± 20%; group B, 25.8% ± 16.4%; group C, 36.9% ± 25.2%) ( P = .27), although significance was not detected for either parameter. Conclusion: This study provides the first evidence of the ability to photopolymerize this novel hydrogel in situ and assess its ability to provide chondrogenic cues for cartilage repair in a small animal model. In vitro chondrogenesis was evident when MSCs were encapsulated in the hydrogel. Clinical Relevance: Cartilage mimetic hydrogel may offer a tissue engineering approach for the treatment of osteochondral lesions.

scholarly journals RADIOLOGICAL STUDY OF MEGACOLON IN TRYPANOSOMA CRUZI INFECTED RATS

2018 ◽  
Vol 31 (1) ◽  
Author(s):  
Carlos Edmundo Rodrigues FONTES ◽  
Ana Paula de ABREU ◽  
Aretuza Zaupa GASPARIM
Keyword(s):  
Trypanosoma Cruzi ◽  
Wistar Rats ◽  
In Vivo Studies ◽  
Proposed Model ◽  
Male Wistar Rats ◽  
Group A ◽  
Time Of Infection ◽  
Group B ◽  
Digital Caliper

ABSTRACT Background: Researches on Chagas disease still use several animals and rats, due to size and susceptibility were preferred by many authors. Aim: To develop an experimental model of megacolon in rats inoculated with the strain Y of Trypanosoma cruzi. Methods: Thirty male Wistar rats were distributed in three groups inoculated with different inoculants: Group A: 600000, Group B: 1000000 and Group C: 1500000 blood trypomastigotes of T. cruzi. Animals were sedated intramuscularly at zero inoculation time (T0) and 60 days after inoculation (T60), to perform the barium enema in order to evaluate the dilatation of the different segments of colon in a comparative study of the measurements obtained, using a digital caliper. Evidence of infection was performed by blood smear collected from the animal’s tail 18 days after inoculation with observation of blood forms. Results: Comparing the intestinal diameter of the inoculated animals with 60,0000 trypomastigotes in the T0 of infection with T60 days after the inoculation, significant dilatation was observed between the proximal, medial and distal segments (p<0.01), indicating the establishment of the megacolon model. In addition, comparing intestinal diameter between the different segments, with in the T0 of infection and the T60 after inoculation, significant alterations were observed (p<0.05). Conclusion: The proposed model was possible for in vivo studies of alterations due to infection by T. cruzi and functional alterations of the colon. In addition, the changes manifested in the colon are not directly proportional to the size of the inoculum, but to the time of infection that the animals were submitted, since the animals inoculated with 60,0000 blood forms were the ones which presented the most significant alterations.

scholarly journals The Neuroprotective Effects of Xenon on Neonatal Rats with White Matter Damage by Regulating Expression of microRNA-210 and HIF-1αThe Neuroprotective Effects of Xenon on Neonatal Rats with White Matter Damage by Regulating Expression of microRNA-210 and HIF-1α

2020 ◽  
Author(s):  
Xiangyun Yin ◽  
Jixiu Zhao ◽  
Jian Jiang ◽  
Hongmin Xi ◽  
Xianghong Li ◽  
...  
Keyword(s):  
White Matter ◽  
Expression Level ◽  
Neonatal Rats ◽  
Rt Pcr ◽  
White Matter Damage ◽  
Neuroprotective Effects ◽  
Brain White Matter ◽  
Group A ◽  
Group B ◽  
Brain Tissues

Abstract Background:Premature infant is a significant health care burden. White matter damage (WMD) is a leading cause of acute mortality and chronic morbidity in preterm. Xenon (Xe) intervention was given to the 3-day-old neonatal rats with brain white matter injury. By detecting the changes in the expression level of microRNA210 and hypoxia inducible factor 1α (HIF-1α) in brain tissue before and after xenon intervention, we can research the molecular basis and the mechanism of neuroprotective on effect of xenon on brain white matter damage in neonatal rats.Methods:Three-day-old SD rats were randomly divided into sham group(Group A, n=24), lipopolysaccharide(LPS)+hypoxia-ischemia(HI) group (Group B, n=24) and LPS+HI+Xe group ( n=72). The onset of Xe inhalation started at 0,2 and 5 hours in subgroups C,D,and E respectively.We investigated the neurobehavioral deficits by performing TUNEL and hematoxylin and eosin (HE) staining and examining the expression of miR-210and HIF-1α in brain tissues via RT-PCR and western blot. Results: Xe treatment improved the histological alterations and decreased the number of apoptotic cells in group C pups.Compared to group A,Detection of miR-210 level by RT-PCR. the expression level of miR-210 in neonatal rats' periventricular tissue increased significantly at all time points in group B (p<0.05).While the expression level of miR-210 in brain tissues of group B was significantly lower at 48h and 72h than that of group C(p<0.05).Similarly,Detection of HIF-1α protein by Western blot. The level of HIF-1α protein in group B brain tissues was significantly higher than that of group A at each time point (p<0.05), Xe treatment resulted in a marked increase in HIF-1α in C,D, and E subgroups (P < 0.05, compared to group B).Conclusions: These results demonstrate that the expression of HIF-1α and miR-210 increased in periventricular tissues and Xe could relieve the white matter damage by up-regulating the expression of HIF-1α and its target gene miR-210.The Xe therapeutic time window was within 5 hours after intervention, the sooner the better.

A positron emission tomography study of cerebrovascular reserve before and after shunt surgery in patients with idiopathic chronic hydrocephalus

1999 ◽  
Vol 91 (4) ◽  
pp. 605-609 ◽  
Author(s):  
Petra M. Klinge ◽  
Georg Berding ◽  
Thomas Brinker ◽  
Wolfram H. Knapp ◽  
Madjid Samii
Keyword(s):  
Positron Emission Tomography ◽  
Emission Tomography ◽  
Chronic Hydrocephalus ◽  
Content Type ◽  
Cerebrovascular Reserve ◽  
Shunt Placement ◽  
Positron Emission ◽  
Group A ◽  
Group B ◽  
Fine Print

Object. In this study the authors use positron emission tomography (PET) to investigate cerebral blood flow (CBF) and cerebrovascular reserve (CVR) in chronic hydrocephalus.Methods. Ten patients whose mean age was 67 ± 10 years (mean ± standard deviation [SD]) were compared with 10 healthy volunteers who were 25 ± 3 years of age. Global CBF and CVR were determined using 15O—H2O and PET prior to shunt placement and 7 days and 7 months thereafter. The CVR was measured using 1 g acetazolamide. Neurological status was assessed based on a score assigned according to the methods of Stein and Langfitt.Seven months after shunt placement, five patients showed clinical improvement (Group A) and five did not (Group B). The average global CBF before shunt deployment was significantly reduced in comparison with the control group (40 ± 8 compared with 61 ± 7 ml/100 ml/minute; mean ± SD, p < 0.01). In Group A the CBF values were significantly lower than in Group B (36 ± 7 compared with 44 ± 8 ml/100 ml/minute; p < 0.05). The CVR before surgery, however, was not significantly different between groups (Group A = 43 ± 21%, Group B = 37 ± 29%). After shunt placement, there was an increase in the CVR in Group A to 52 ± 37% after 7 days and to 68 ± 47% after 7 months (p < 0.05), whereas in Group B the CVR decreased to 14 ± 18% (p < 0.05) after 7 days and returned to the preoperative level (39 ± 6%) 7 months after shunt placement.Conclusions. The preliminary results indicate that a reduced baseline CBF before surgery does not indicate a poor prognosis. Baseline CBF before shunt placement and preoperative CVR are not predictive of clinical outcome. A decrease in the CVR early after shunt placement, however, is related to poor late clinical outcome, whereas early improvement in the CVR after shunt placement indicates a good prognosis.

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