scholarly journals Intra-individual dynamic comparison of 18F-PSMA-11 and 68Ga-PSMA-11 in LNCaP xenograft bearing mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sarah Piron ◽  
Jeroen Verhoeven ◽  
Benedicte Descamps ◽  
Ken Kersemans ◽  
Kathia De Man ◽  
...  

AbstractRecently, a 18F-labeled derivative of the widely used 68Ga-PSMA-11 was developed for PET imaging of prostate cancer. Although 18F-PSMA-11 has already been evaluated in a Phase I and Phase II clinical trial, preclinical evaluation of this radiotracer is important for further understanding its dynamic behavior. Saturation binding experiments were conducted by incubation of LNCaP cells with 18F-PSMA-11 or 68Ga-PSMA-11 for 1 h, followed by determination of the specific and aspecific binding. Mice bearing LNCaP or PC-3 xenografts each received ± 3.7 MBq 18F-PSMA-11 and 68Ga-PSMA-11 followed by dynamic acquisition of 2.5 h as well as ± 15 MBq 18F-FDG followed by static acquisition at 1 h post injection (p.i.). Uptake was evaluated by comparison of uptake parameters (SUVmean, SUVmax, TBRmean and TBRmax). Mice underwent ex vivo biodistribution where 18F-PSMA-11 activity was measures in excretory organs (kidneys, bladder and liver) as well as bone fragments (femur, humerus, sternum and skull) to evaluate bone uptake. The dissociation constant (Kd) of 18F-PSMA-11 and 68Ga-PSMA-11 was 2.95 ± 0.87 nM and 0.49 ± 0.20 nM, respectively. Uptake parameters were significantly higher in LNCaP compared to PC-3 xenografts for both 18F-PSMA-11 and 68Ga-PSMA-11, while no difference was found for 18F-FDG uptake (except for SUVmax). Tumor uptake of 18F-PSMA-11 showed a similar trend over time as 68Ga-PSMA-11, although all uptake parameter curves of the latter were considerably lower. When comparing early (60 min p.i.) to delayed (150 min p.i.) imaging for both radiotracers individually, TBRmean and TBRmax were significantly higher at the later timepoint, as well as the SUVmax of 68Ga-PSMA-11. The highest %ID/g was determined in the kidneys (94.0 ± 13.6%ID/g 1 h p.i.) and the bladder (6.48 ± 2.18%ID/g 1 h p.i.). No significant increase in bone uptake was seen between 1 and 2 h p.i. Both radiotracers showed high affinity for the PSMA receptor. Over time, all uptake parameters were higher for 18F-PSMA-11 compared to 68Ga-PSMA-11. Delayed imaging with the latter may improve tumor visualization, while no additional benefits could be found for late 18F-PSMA-11 imaging. Ex vivo biodistribution demonstrated fast renal clearance of 18F-PSMA-11 as well as no significant increase in bone uptake.

Author(s):  
Olga Wronikowska ◽  
Maria Zykubek ◽  
Agnieszka Michalak ◽  
Anna Pankowska ◽  
Paulina Kozioł ◽  
...  

AbstractMephedrone is a widely used drug of abuse, exerting its effects by interacting with monoamine transporters. Although this mechanism has been widely studied heretofore, little is known about the involvement of glutamatergic transmission in mephedrone effects. In this study, we comprehensively evaluated glutamatergic involvement in rewarding effects of mephedrone using an interdisciplinary approach including (1) behavioural study on effects of memantine (non-selective NMDA antagonist) on expression of mephedrone-induced conditioned place preference (CPP) in rats; (2) evaluation of glutamate concentrations in the hippocampus of rats following 6 days of mephedrone administration, using in vivo magnetic resonance spectroscopy (MRS); and (3) determination of glutamate levels in the hippocampus of rats treated with mephedrone and subjected to MRS, using ion-exchange chromatography. In the presented research, we confirmed priorly reported mephedrone-induced rewarding effects in the CPP paradigm and showed that memantine (5 mg/kg) was able to reverse the expression of this effect. MRS study showed that subchronic mephedrone administration increased glutamate level in the hippocampus when measured in vivo 24 h (5 mg/kg, 10 mg/kg and 20 mg/kg) and 2 weeks (5 mg/kg and 20 mg/kg) after last injection. Ex vivo chromatographic analysis did not show significant changes in hippocampal glutamate concentrations; however, it showed similar results as obtained in the MRS study proving its validity. Taken together, the presented study provides new insight into glutamatergic involvement in rewarding properties of mephedrone.


2021 ◽  
Vol 96-97 ◽  
pp. S106-S107
Author(s):  
Elisavet Lambidis ◽  
Chun Chieh Chen ◽  
Mo Baikoghli ◽  
Surachet Imlimthan ◽  
Mirkka Sarparanta ◽  
...  

2020 ◽  
Vol 3 (4) ◽  
pp. 67
Author(s):  
Julie Brogaard Larsen ◽  
Anne-Mette Hvas

Disturbance in the balance between fibrin formation and fibrinolysis can lead to either bleeding or thrombosis; however, our current routine coagulation assays are not sensitive to altered fibrinolysis. The clot formation and lysis assay is a dynamic plasma-based analysis that assesses the patient’s capacity for fibrin formation and fibrinolysis by adding an activator of coagulation as well as fibrinolysis to plasma and measuring ex vivo fibrin clot formation and breakdown over time. This assay provides detailed information on the fibrinolytic activity but is currently used for research only, as the assay is prone to inter-laboratory variation and as it demands experienced laboratory technicians as well as specialized personnel to validate and interpret the results. Here, we describe a protocol for the clot formation and lysis assay used at our research laboratory.


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 ◽  
...  

2010 ◽  
Vol 79 (4) ◽  
pp. 613-620 ◽  
Author(s):  
Lucie Urbanová ◽  
Robert Srnec ◽  
Pavel Proks ◽  
Ladislav Stehlík ◽  
Zdeněk Florian ◽  
...  

The study deals with the determination of mechanical properties, namely resistance to bending forces, of flexible buttress osteosynthesis using two different bone-implant constructs stabilizing experimental segmental femoral bone defects (segmental ostectomy) in a miniature pig ex vivo model using 4.5 mm titanium LCP and a 3 mm intramedullary pin (“plate and rod” construct) (PR-LCP), versus the 4.5 mm titanium LCP alone (A-LCP). The “plate and rod” fixation (PR-LCP) of the segmental femoral defect is significantly more resistant (p < 0.05) to bending forces (200 N, 300 N, and 500 N) than LCP alone (A-LCP). Stabilisation of experimental segmental lesions of the femoral diaphysis in miniature pigs by flexible bridging osteosynthesis 4.5 mm LCP in combination with the “plate and rod” construct appears to be a suitable fixation of non-reducible fractures where considerable strain of the implants by bending forces can be assumed. These findings will be used in upcoming in vivo experiments in the miniature pig to investigate bone defect healing after transplantation of mesenchymal stem cells in combination with biocompatible scaffolds.


2007 ◽  
Author(s):  
K. Bamert ◽  
R. Kallenbach ◽  
M. Hilchenbach ◽  
C. W. Smith
Keyword(s):  

2015 ◽  
Vol 28 (05) ◽  
pp. 295-300 ◽  
Author(s):  
M. D. O’Donnell ◽  
G. Bobe ◽  
R. P. Scholz ◽  
J. E. Wiest ◽  
S. Nemanic ◽  
...  

Summary Objectives: To compare the results of femoral head and neck excision (FHNE) ostectomy performed by two novice veterinarians using an osteotome and mallet or microsagittal saw. Methods: In this ex vivo cadaveric study, hindlimbs of eight canine cadavers were randomized to FHNE with osteotome or micro sagittal saw as performed by two recently graduated veterinarians. The hindimbs were imaged by computed tomography (CT) before and after the osteotomy. Post FHNE CT images were evaluated by a board certified radiologist blinded to the ostectomy technique for assessment of the number of bone fragments, fissures, smoothness of osteotomy margination, and volume of residual fe-moral neck. Results: Femoral head and neck excision performed with the osteotome produced more peri-ostectomy bone fragments, cortical fissures, irregular margins, and residual femoral neck volume, compared with osteotomy using a saw. Clinical relevance: Compared to FHNE performed with a sagittal saw, osteotome FHNE resulted in a greater bone trauma and residual neck bone volume, which would require post-ostectomy modification in a clinical setting.


2022 ◽  
Vol 8 ◽  
Author(s):  
James A. Garnett ◽  
Joseph Atherton

Historically proteins that form highly polymeric and filamentous assemblies have been notoriously difficult to study using high resolution structural techniques. This has been due to several factors that include structural heterogeneity, their large molecular mass, and available yields. However, over the past decade we are now seeing a major shift towards atomic resolution insight and the study of more complex heterogenous samples and in situ/ex vivo examination of multi-subunit complexes. Although supported by developments in solid state nuclear magnetic resonance spectroscopy (ssNMR) and computational approaches, this has primarily been due to advances in cryogenic electron microscopy (cryo-EM). The study of eukaryotic microtubules and bacterial pili are good examples, and in this review, we will give an overview of the technical innovations that have enabled this transition and highlight the advancements that have been made for these two systems. Looking to the future we will also describe systems that remain difficult to study and where further technical breakthroughs are required.


2001 ◽  
Vol 33 (4) ◽  
pp. 529-549 ◽  
Author(s):  
Y. LE STRAT ◽  
J. C. THALABARD

A large multicentre epidemiological study was carried out by WHO between 1991 and 1995 to analyse the duration of lactational amenorrhoea in relation to breast-feeding. The main results of this analysis, which used classical statistical modelling, have been already published. However, some specific aspects of the postpartum fertility amenorrhoea and breast-feeding covariates, and more specifically the observed progressive exhaustion of the breast-feeding inhibitory effect on the reproductive axis, may justify a closer look at the validity of the statistical tools. Indeed, as has already been emphasized, analysis of large longitudinal data sets in reproduction often faces three difficulties: (i) the precise determination of the event of interest, (ii) the way to handle the time evolution of both the studied variables and their effect on the event of interest and (iii) the often discrete nature of the data and the associated problem of tied events. The first objective of the present work was to give additional insights into the estimation and quantification of the dynamics of the effect of breast-feeding over time, considering this covariate either as fixed or time-dependent. The second objective was to show how to perform the analyses using corresponding adapted procedures in widely available statistical packages, without the need for acquiring particular programming skills.


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