scholarly journals A Comparative68Ga-Citrate and68Ga-Chloride PET/CT Imaging ofStaphylococcus aureusOsteomyelitis in the Rat Tibia

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Petteri Lankinen ◽  
Tommi Noponen ◽  
Anu Autio ◽  
Pauliina Luoto ◽  
Janek Frantzèn ◽  
...  
Keyword(s):  
Bone Healing ◽  
Ex Vivo ◽  
Quantitative Computed Tomography ◽  
Conventional Radiography ◽  
Peripheral Quantitative Computed Tomography ◽  
Experimental Models ◽  
Ct Imaging ◽  
Microbiological Analysis ◽  
Pet Ct

There may be some differences in thein vivobehavior of68Ga-chloride and68Ga-citrate leading to different accumulation profiles. This study compared68Ga-citrate and68Ga-chloride PET/CT imaging under standardized experimental models.Methods.DiffuseStaphylococcus aureustibial osteomyelitis and uncomplicated bone healing rat models were used (n=32). Two weeks after surgery, PET/CT imaging was performed on consecutive days using68Ga-citrate or68Ga-chloride, and tissue accumulation was confirmed byex vivoanalysis. In addition, peripheral quantitative computed tomography and conventional radiography were performed. Osteomyelitis was verified by microbiological analysis and specimens were also processed for histomorphometry.Results.In PET/CT imaging, theSUVmaxof68Ga-chloride and68Ga-citrate in the osteomyelitic tibias (3.6 ± 1.4 and 4.7 ± 1.5, resp.) were significantly higher (P=0.0019andP=0.0020, resp.) than in the uncomplicated bone healing (2.7 ± 0.44 and 2.5 ± 0.49, resp.). In osteomyelitic tibias, theSUVmaxof68Ga-citrate was significantly higher than the uptake of68Ga-chloride (P=0.0017). In animals with uncomplicated bone healing, no difference in theSUVmaxof68Ga-chloride or68Ga-citrate was seen in the operated tibias.Conclusions.This study further corroborates the use of68Ga-citrate for PET imaging of osteomyelitis.

scholarly journals Monitoring the Early Response of Fulvestrant Plus Tanshinone IIA Combination Therapy to Estrogen Receptor-Positive Breast Cancer by Longitudinal 18F-FES PET/CT

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
SiMin He ◽  
MingWei Wang ◽  
YongPing Zhang ◽  
JianMin Luo ◽  
YingJian Zhang
Keyword(s):  
Combination Therapy ◽  
Ex Vivo ◽  
Early Response ◽  
Ct Imaging ◽  
Tanshinone Iia ◽  
Breast Cancers ◽  
Antitumor Effects ◽  
Pet Ct ◽  
Er Positive

Endocrine monotherapy of breast cancers is generally hampered by the primary/acquired resistance and adverse sides in clinical settings. Herein, advantaging the multitargeting antitumor effects and normal organ-protecting roles of Chinese herbal medicine, the aim of this study was to investigate the enhanced synergistic efficacy of fulvestrant plus Tan IIA combination therapy in ER-positive breast cancers and to monitor the early response by longitudinal 18F-FES PET/CT imaging. The experimental results showed FUL + Tan IIA combination therapy significantly inhibited tumor growth of ER-positive ZR-75-1 tumor xenografts and exhibited distinct antitumor effects at an earlier time point after treatment than did the monotherapy of FUL or Tan IIA. Moreover, 18F-FES PET/CT imaging competently monitored the early response of FUL + Tan IIA combination therapy. The quantitative 18F-FES %ID/gmax in vivo was further confirmed by and correlated well with ERα expression ex vivo. In conclusion, the synergic effect of FUL + Tan IIA combination therapy to ER-positive breast cancers was verified in the preclinical tumor models and the early treatment response could be monitored by 18F-FES PET/CT.

scholarly journals Upscaling of In Vivo HR-pQCT Images Enables Accurate Simulations of Human Microstructural Bone Adaptation

2020 ◽  
Author(s):  
Nicholas Ohs ◽  
Duncan C. Tourolle né Betts ◽  
Penny R. Atkins ◽  
Stephanie Sebastian ◽  
Bert van Rietbergen ◽  
...  
Keyword(s):  
High Resolution ◽  
In Silico ◽  
Ex Vivo ◽  
Quantitative Computed Tomography ◽  
Ground Truth ◽  
Peripheral Quantitative Computed Tomography ◽  
Bone Adaptation ◽  
Bone Diseases ◽  
Clinical Models

AbstractIn silico trials of treatments in a virtual physiological human (VPH) would revolutionize research in the biomedical field. Hallmarks of bone disease and treatments can already be simulated in pre-clinical models and in ex vivo data of humans using microstructural bone adaptation simulations. The increasing availability of in vivo high resolution peripheral quantitative computed tomography (HR-pQCT) images provides novel opportunities to validate and ultimately utilize microstructural bone adaptation simulations to improve our understanding of bone diseases and move towards in silico VPH decision support systems for clinicians.In the present study, we investigated if microstructural bone adaptation simulations of in vivo human HR-pQCT images yielded accurate results. Since high-resolution ground truth images cannot be obtained in vivo, we applied an ex vivo approach to study resolution dependence and the effect of upscaling on morphometric accuracy. To address simulation initialisation issues, we developed an input regularisation approach to reduce initialisation shocks observed in microstructural bone adaptation simulations and evaluated upscaling as a way to improve the accuracy of model inputs. Finally, we compared our ex vivo results to simulations run on in vivo images to investigate whether in vivo image artefacts further affect simulation outcomes.

scholarly journals Preclinical and Exploratory Clinical Studies of Novel 68Ga-labeled ᴅ-Peptide Antagonist for PET Imaging of TIGIT Expression in Cancers

2021 ◽  
Author(s):  
Xiaobo Wang ◽  
Ming Zhou ◽  
Bei Chen ◽  
Huanhuan Liu ◽  
Jianyang Fang ◽  
...  
Keyword(s):  
Pilot Study ◽  
Pet Imaging ◽  
Ex Vivo ◽  
Ct Imaging ◽  
Whole Body ◽  
Binding Assays ◽  
Pet Ct ◽  
Peptide Antagonist

Abstract Purpose While TIGIT has been propelled under the spotlight as a next-generation target in cancer immunotherapy, anti-TIGIT therapy seems to be promising for a fraction of patients in clinical trials. Therefore, patient stratification is critical for this therapy, which could benefit from a whole-body, non-invasive and quantitative evaluation of TIGIT expression in cancers. In this study, a 68Ga-labeled ᴅ-peptide antagonist, 68Ga-GP12, was developed and validated for PET imaging of TIGIT expression in vitro, in vivo, and first-in-human pilot study. Methods The ᴅ-enantiomer peptide antagonists were modified and radiolabeled with 68Ga. In vitro binding assays were performed in human peripheral blood mononuclear cells (PBMCs) to assess their affinity and specificity. The imaging capacity, biodistribution, pharmacokinetics, and radiation dosimetry were investigated in vivo. Flow cytometry, autoradiography, and immunohistochemical staining were used to confirm the expression of TIGIT ex vivo. The safety and potential of 68Ga-GP12 for PET/CT imaging of TIGIT expression were further evaluated in a first-in-human pilot study with advanced NSCLC. Results 68Ga-labeled ᴅ-peptides were conveniently produced with high radiochemical yields,radiochemical purity and molar activities. In vitro binding assays demonstrated 68Ga-GP12 has favorable affinity and specificity for TIGIT with a KD of 37.28 nM. In vivo and ex vivo studies demonstrated the favorable pharmacokinetics of 68Ga-GP12 for PET imaging of TIGIT expression with high tumor uptake of 4.22 ± 0.68 %ID/g and the tumor-to-muscle ratio of 12.94 ± 2.64 at 60 min post-injection. The primary and metastatic lesions found in the first-in-human studies of 68Ga-GP12 PET/CT imaging were comparable to that in 18F-FDG PET/CT imaging. Moreover, the inhomogenous intra-and-inter-tumoral uptake of 68Ga-GP12 was presented, reflecting the heterogeneity of TIGIT expression levels. Conclusion 68Ga-GP12 is a promising radiotracer for PET imaging of TIGIT expression in cancers, indicating its potential as a potential companion diagnostic for anti-TIGIT therapies.

Abstract 18873: Al 18 F-NOTA-folate Accumulates in Atherosclerotic Plaques and Can be Detected by PET/CT

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Johanna M Silvola ◽  
Xiang-Guo Li ◽  
Jenni Virta ◽  
Guru Prasad Padmasola ◽  
Päivi Marjamäki ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Folate Receptor ◽  
Specific Radioactivity ◽  
Experimental Models ◽  
Atherosclerotic Plaques ◽  
Pet Tracer ◽  
Contrast Enhanced Ct ◽  
Pet Ct ◽  
Atheromatous Plaques

Introduction:Macrophages are a major cell type in inflamed atherosclerotic plaques. Since folate receptor β (FR-β) is highly expressed in activated macrophages, we hypothesized that it might serve as a new marker for inflamed atherosclerotic plaques. Hypothesis: We aimed at evaluating a FR-β targeted PET tracer, Al 18 F NOTA-Folate, for the detection of inflamed atherosclerotic plaques. Methods:Atherosclerotic mice deficient for low density lipoprotein receptor (LDLR -/- ApoB 100/100 , n=12), C57BL control mice (n=9), and Watanabe rabbits (n=4) with endothelial denudation-induced atherosclerosis in the aorta were used. Biodistribution of Al 18 F-NOTA-Folate (specific radioactivity 130 GMq/μmol) was investigated in vivo by PET/contrast enhanced CT and ex vivo by gamma counting and autoradiography of aortic sections. In addition, prior to Al 18 F-NOTA-Folate study, the Watanabe rabbits were PET/CT imaged with 18 F-FDG. Results:Atherosclerotic mice demonstrated large and macrophage-rich atheromatous plaques in the aorta. The in vivo PET/CT revealed significantly higher uptake of Al 18 F-NOTA-Folate in the aortic arch of atherosclerotic mice compared to controls (aorta-to-blood ratio 1.5±0.3 vs. 0.7±0.2, P <0.0001), which were verified by ex vivo measurements. Autoradiography confirmed focally increased uptake of Al 18 F-NOTA-Folate in the atherosclerotic plaques (plaque-to-normal vessel wall ratio 2.6±0.7, P <0.0001). Competitive study with excess of unlabelled folate reduced Al 18 F-NOTA-Folate uptake in the aorta by app. 80% and thus verified the specificity of its binding. In the rabbit aorta, the PET/CT showed a strong focal in vivo uptake of Al 18 F-NOTA-Folate co-localizing with an atherosclerotic abdominal aorta with highest aorta-to-blood ratio of 6.0. For comparison, with 18 F-FDG the ratio was 2.4 in the same area. Conclusions: Al 18 F-NOTA-Folate, targeting FR-β, accumulates in macrophage-rich atherosclerotic plaques, which can be detected in vivo by PET/CT in experimental models of atherosclerosis. Further development of the tracer for imaging of patients with atherosclerosis is warranted.

scholarly journals Aerosolized In Vivo 3D Localization of Nose-to-Brain Nanocarrier Delivery Using Multimodality Neuroimaging in a Rat Model—Protocol Development

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 391
Author(s):  
Michael C. Veronesi ◽  
Brian D. Graner ◽  
Shih-Hsun Cheng ◽  
Marta Zamora ◽  
Hamideh Zarrinmayeh ◽  
...  
Keyword(s):  
Rat Model ◽  
Ex Vivo ◽  
Region Of Interest ◽  
Ct Imaging ◽  
Pet Tracer ◽  
Positron Emission ◽  
Pet Ct ◽  
Activity Measurements ◽  
The Brain

The fate of intranasal aerosolized radiolabeled polymeric micellar nanoparticles (LPNPs) was tracked with positron emission tomography/computer tomography (PET/CT) imaging in a rat model to measure nose-to-brain delivery. A quantitative temporal and spatial testing protocol for new radio-nanotheranostic agents was sought in vivo. LPNPs labeled with a zirconium 89 (89Zr) PET tracer were administered via intranasal or intravenous delivery, followed by serial PET/CT imaging. After 2 h of continuous imaging, the animals were sacrificed, and the brain substructures (olfactory bulb, forebrain, and brainstem) were isolated. The activity in each brain region was measured for comparison with the corresponding PET/CT region of interest via activity measurements. Serial imaging of the LPNPs (100 nm PLA–PEG–DSPE+89Zr) delivered intranasally via nasal tubing demonstrated increased activity in the brain after 1 and 2 h following intranasal drug delivery (INDD) compared to intravenous administration, which correlated with ex vivo gamma counting and autoradiography. Although assessment of delivery from nose to brain is a promising approach, the technology has several limitations that require further development. An experimental protocol for aerosolized intranasal delivery is presented herein, which may provide a platform for better targeting the olfactory epithelium.

scholarly journals Ocular Toxoplasmosis: Mechanisms of Retinal Infection and Experimental Models

Parasitologia ◽  
2021 ◽  
Vol 1 (2) ◽  
pp. 50-60
Author(s):  
Veronica Rodriguez Fernandez ◽  
Giovanni Casini ◽  
Fabrizio Bruschi
Keyword(s):  
Ex Vivo ◽  
Cell Damage ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Treatment Strategies ◽  
Experimental Models ◽  
Ocular Toxoplasmosis ◽  
Cell Infection

Ocular toxoplasmosis (OT) is caused by the parasite Toxoplasma gondii and affects many individuals throughout the world. Infection may occur through congenital or acquired routes. The parasites enter the blood circulation and reach both the retina and the retinal pigment epithelium, where they may cause cell damage and cell death. Different routes of access are used by T. gondii to reach the retina through the retinal endothelium: by transmission inside leukocytes, as free parasites through a paracellular route, or after endothelial cell infection. A main feature of OT is the induction of an important inflammatory state, and the course of infection has been shown to be influenced by the host immunogenetics. On the other hand, there is evidence that the T. gondii phenotype also has an impact on the distribution of the pathology in different areas. Although considerable knowledge has been acquired on OT, a deeper knowledge of its mechanisms is necessary to provide new, more targeted treatment strategies. In particular, in addition to in vitro and in vivo experimental models, organotypic, ex vivo retinal explants may be useful in this direction.

scholarly journals Radiation Dosimetry of a Novel Adenosine A2A Receptor Radioligand [11C]Preladenant Based on PET/CT Imaging and Ex Vivo Biodistribution in Rats

2016 ◽  
Vol 19 (2) ◽  
pp. 289-297 ◽  
Author(s):  
Xiaoyun Zhou ◽  
Philip H. Elsinga ◽  
Shivashankar Khanapur ◽  
Rudi A. J. O. Dierckx ◽  
Erik F. J. de Vries ◽  
...  
Keyword(s):  
Radiation Dosimetry ◽  
Ex Vivo ◽  
Ct Imaging ◽  
Adenosine A2a Receptor ◽  
Pet Ct ◽  
A2a Receptor ◽  
Adenosine A2a ◽  
Ex Vivo Biodistribution
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