scholarly journals In Vivo Imaging of Peripheral Benzodiazepine Receptors in Mouse Lungs: A Biomarker of Inflammation

2005 ◽  
Vol 4 (4) ◽  
pp. 7290.2005.05133 ◽  
Author(s):  
Matthew J. Hardwick ◽  
Ming-Kai Chen ◽  
Kwamena Baidoo ◽  
Martin G. Pomper ◽  
Tomás R. Guilarte
Keyword(s):  
In Vivo Imaging ◽  
Ex Vivo ◽  
Inflammatory Diseases ◽  
Imaging Techniques ◽  
Benzodiazepine Receptors ◽  
Small Animal ◽  
Small Animal Pet ◽  
Planar Imaging ◽  
Peripheral Benzodiazepine Receptors

The ability to visualize the immune response with radioligands targeted to immune cells will enhance our understanding of cellular responses in inflammatory diseases. Peripheral benzodiazepine receptors (PBR) are present in monocytes and neutrophils as well as in lung tissue. We used lipopolysaccharide (LPS) as a model of inflammation to assess whether the PBR could be used as a noninvasive marker of inflammation in the lungs. Planar imaging of mice administrated 10 or 30 mg/kg LPS showed increased [123I]-( R)-PK11195 radioactivity in the thorax 2 days after LPS treatment relative to control. Following imaging, lungs from control and LPS-treated mice were harvested for ex vivo gamma counting and showed significantly increased radioactivity above control levels. The specificity of the PBR response was determined using a blocking dose of nonradioactive PK11195 given 30 min prior to radiotracer injection. Static planar images of the thorax of nonradioactive PK11195 pretreated animals showed a significantly lower level of radiotracer accumulation in control and in LPS-treated animals ( p < .05). These data show that LPS induces specific increases in PBR ligand binding in the lungs. We also used in vivo small-animal PET studies to demonstrate increased [11C]-( R)-PK11195 accumulation in the lungs of LPS-treated mice. This study suggests that measuring PBR expression using in vivo imaging techniques may be a useful biomarker to image lung inflammation.

In vivo imaging of brain lesions with [11C]CLINME, a new PET radioligand of peripheral benzodiazepine receptors

Glia ◽  
2007 ◽  
Vol 55 (14) ◽  
pp. 1459-1468 ◽  
Author(s):  
Hervé Boutin ◽  
Fabien Chauveau ◽  
Cyrille Thominiaux ◽  
Bertrand Kuhnast ◽  
Marie-Claude Grégoire ◽  
...  
Keyword(s):  
In Vivo Imaging ◽  
Benzodiazepine Receptors ◽  
Brain Lesions ◽  
Peripheral Benzodiazepine Receptors

Implementation of 89Zr production and in vivo imaging of B-cells in mice with 89Zr-labeled anti-B-cell antibodies by small animal PET/CT

2011 ◽  
Vol 69 (6) ◽  
pp. 852-857 ◽  
Author(s):  
Martin Walther ◽  
Peter Gebhardt ◽  
Philipp Grosse-Gehling ◽  
Lydia Würbach ◽  
Ingo Irmler ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
In Vivo Imaging ◽  
Small Animal ◽  
Small Animal Pet ◽  
Animal Pet ◽  
Pet Ct

scholarly journals A Semi Rigid Novel Hydroxamate AMPED-Based Ligand for 89Zr PET Imaging

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5819
Author(s):  
Lisa Russelli ◽  
Francesco De Rose ◽  
Loredana Leone ◽  
Sybille Reder ◽  
Markus Schwaiger ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Ex Vivo ◽  
Small Animal ◽  
Biologically Active ◽  
Small Animal Pet ◽  
Organ Distribution ◽  
Complexing Agent ◽  
Distribution Studies

In this work, we designed, developed, characterized, and investigated a new chelator and its bifunctional derivative for 89Zr labeling and PET-imaging. In a preliminary study, we synthesized two hexadentate chelators named AAZTHAS and AAZTHAG, based on the seven-membered heterocycle AMPED (6-amino-6-methylperhydro-1,4-diazepine) with the aim to increase the rigidity of the 89Zr complex by using N-methyl-N-(hydroxy)succinamide or N-methyl-N-(hydroxy)glutaramide pendant arms attached to the cyclic structure. N-methylhydroxamate groups are the donor groups chosen to efficiently coordinate 89Zr. After in vitro stability tests, we selected the chelator with longer arms, AAZTHAG, as the best complexing agent for 89Zr presenting a stability of 86.4 ± 5.5% in human serum (HS) for at least 72 h. Small animal PET/CT static scans acquired at different time points (up to 24 h) and ex vivo organ distribution studies were then carried out in healthy nude mice (n = 3) to investigate the stability and biodistribution in vivo of this new 89Zr-based complex. High stability in vivo, with low accumulation of free 89Zr in bones and kidneys, was measured. Furthermore, an activated ester functionalized version of AAZTHAG was synthesized to allow the conjugation with biomolecules such as antibodies. The bifunctional chelator was then conjugated to the human anti-HER2 monoclonal antibody Trastuzumab (Tz) as a proof of principle test of conjugation to biologically active molecules. The final 89Zr labeled compound was characterized via radio-HPLC and SDS-PAGE followed by autoradiography, and its stability in different solutions was assessed for at least 4 days.

scholarly journals Iodine-124 PET quantification of organ-specific delivery and expression of NIS-encoding RNA

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Matthias Miederer ◽  
Stefanie Pektor ◽  
Isabelle Miederer ◽  
Nicole Bausbacher ◽  
Isabell Sofia Keil ◽  
...  
Keyword(s):  
Cell Lines ◽  
Ex Vivo ◽  
Small Animal ◽  
Protein Translation ◽  
The Body ◽  
Small Animal Pet ◽  
Animal Pet ◽  
Organ Specific

Abstract Background RNA-based vaccination strategies tailoring immune response to specific reactions have become an important pillar for a broad range of applications. Recently, the use of lipid-based nanoparticles opened the possibility to deliver RNA to specific sites within the body, overcoming the limitation of rapid degradation in the bloodstream. Here, we have investigated whether small animal PET/MRI can be employed to image the biodistribution of RNA-encoded protein. For this purpose, a reporter RNA coding for the sodium-iodide-symporter (NIS) was in vitro transcribed in cell lines and evaluated for expression. RNA-lipoplex nanoparticles were then assembled by complexing RNA with liposomes at different charge ratios, and functional NIS protein translation was imaged and quantified in vivo and ex vivo by Iodine-124 PET upon intravenous administration in mice. Results NIS expression was detected on the membrane of two cell lines as early as 6 h after transfection and gradually decreased over 48 h. In vivo and ex vivo PET/MRI of anionic spleen-targeting or cationic lung-targeting NIS-RNA lipoplexes revealed a visually detectable rapid increase of Iodine-124 uptake in the spleen or lung compared to control-RNA-lipoplexes, respectively, with minimal background in other organs except from thyroid, stomach and salivary gland. Conclusions The strong organ selectivity and high target-to-background acquisition of NIS-RNA lipoplexes indicate the feasibility of small animal PET/MRI to quantify organ-specific delivery of RNA.

In vivo imaging and quantitative analysis of TSPO in rat peripheral tissues using small-animal PET with [18F]FEDAC

2010 ◽  
Vol 37 (7) ◽  
pp. 853-860 ◽  
Author(s):  
Kazuhiko Yanamoto ◽  
Katsushi Kumata ◽  
Masayuki Fujinaga ◽  
Nobuki Nengaki ◽  
Makoto Takei ◽  
...  
Keyword(s):  
Quantitative Analysis ◽  
In Vivo Imaging ◽  
Small Animal ◽  
Small Animal Pet ◽  
Peripheral Tissues ◽  
Animal Pet

scholarly journals Preclinical and clinical study on [18F]DRKXH1: a novel β-amyloid PET tracer for Alzheimer’s disease

2021 ◽  
Author(s):  
MiaoMiao Xu ◽  
Jun Guo ◽  
JiaCheng Gu ◽  
LinLin Zhang ◽  
ZiHao Liu ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Ex Vivo ◽  
Small Animal ◽  
Small Animal Pet ◽  
Animal Pet ◽  
In Vitro Autoradiography ◽  
Healthy Control ◽  
The Brain

Abstract Background The deposition of β-amyloid (Aβ) in the brain is a biomarker of Alzheimer’s disease (AD). Highly sensitive Aβ positron emission tomography (PET) imaging plays an essential role in diagnosing and evaluating the therapeutic effects of AD. Aim To synthesize a new Aβ tracer [18F]DRKXH1 (5-(4-(6-(2-[18]fluoroethoxy)ethoxy)imidazo[1,2-alpha]pyridin-2-yl)phenyl) and evaluate the tracer performance by biodistribution analysis, in vivo small-animal PET-CT dynamic scan, ex vivo and in vitro autoradiography, and PET in human subjects. Methods [18F]DRKXH1 was synthesized automatically by the GE FN module. Log D (pH 7.4) and biodistribution of [18F]DRKXH1 were investigated. Small-animal-PET was used for [18F]DRKXH1 and [18F]AV45 imaging study in AD transgenic mice (APPswe/PSEN1dE9) and age-matched normal mice. The distribution volume ratios (DVR) and standardized uptake value ratios (SUVRs) were calculated with the cerebellum as the reference region. The deposition of Aβ plaques in the brain of AD transgenic mice was determined by ex vivo autoradiography and immunohistochemistry. In vitro autoradiography was performed in the postmortem brain sections of AD patients and healthy controls. Two healthy control subjects and one AD patient was subjected to in vivo PET study using [18F]DRKXH1. Results The yield of [18F]DRKXH1 was 40%, and the specific activity was 156.64 ± 11.55 GBq/μmol. [18F]DRKXH1 was mainly excreted through the liver and kidney. The small-animal PET study showed high initial brain uptake and rapid washout of [18F]DRKXH1. The concentration of [18F]DRKXH1 was detected in the cortex and hippocampus of AD transgenic mice brain. The cortex DVR of AD transgenic mice was higher than that of WT mice (P < 0.0001). Moreover, the SUVRs of AD transgenic mice were higher than those of WT mice based on the 0–60-min dynamic scanning. In vitro autoradiography showed a significant concentration of tracer in the Aβ plaque-rich areas in the brain of AD transgenic mice. The DVR value of [18F]-DRKXH1 is higher than that of [18F]-AV45 (1.29 ± 0.05 vs. 1.05 ± 0.08; t = 5.33, P = 0.0003). Autoradiography of postmortem human brain sections showed [18F]DRKXH1-labeled Aβ plaques in the AD brain. The AD patients had high retention in cortical regions, while healthy control subjects had uniformly low radioactivity uptake. Conclusions [18F]DRKXH1 is an Aβ tracer with high sensitivity in preclinical study and has the potential for in vivo detection of the human brain.

A Small Animal In Vivo Imaging Model of Expanded vs. Unexpanded UCB Stem Cells Reveals Differential Patterns of Engraftment.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1191-1191
Author(s):  
David Steiner ◽  
Simon N. Robinson ◽  
William K. Decker ◽  
Frank C. Marini ◽  
Elizabeth J. Shpall ◽  
...  
Keyword(s):  
Stem Cells ◽  
In Vivo Imaging ◽  
Cultured Cells ◽  
Ex Vivo ◽  
Small Animal ◽  
Firefly Luciferase ◽  
Pathologic Evaluation ◽  
Imaging Model ◽  
Cd34 Cells

Abstract INTRODUCTION: Use of HLA-mismatched umbilical cord blood (UCB) allows transplant of patients who lack related HLA identical or matched unrelated donors. A major disadvantage of UCB is the limited number of stem cells available within the graft, a contributor to delayed engraftment, especially in adults. Two strategies have been adopted clinically in an attempt to overcome this barrier. 1. ex vivo expansion of some or all of critical graft subfractions; 2. transplantation of two different UCB grafts. These two strategies are not mutually exclusive and are also sometimes used in combination. Little is known about the basic biology that underlies the differential migration and homing of the graft components. To study the biology of complex UCB transplants, we have developed a small animal in vivo imaging model. METHODS: CD34-selected UCB cells were transduced overnight with a lentiviral construct consisting of GFP or a firefly luciferase/GFP fusion. After 24 hours, SCF, FLT3, G-CSF, and thrombopoietin were added and the cells were cultured for 3 to 8 days. All cultured cells were then injected into non-lethally irradiated, immunocompetent mice (NOD/SCID/IL-2Rγ − /−). Transduced cells were tracked weekly by bioluminescent imaging. RESULTS: On culture day 3, >99% of cells remained CD34+ and no expansion was observed. After expansion in culture between days 3 and 8, 19% +/− 18.5% of transduced cells were GFP+CD45+ (n= 8). Cells cultured for three days (non-expanded) (3-11x105 CD34+ cells/3-8.6x104 GFP+) were able to create a detectable engraftment signal by post-transplant day 8. The engraftment signal was delayed until day 10 when an 8-fold excess of the expanded cultured cells (4.2x106 total consisting of 1.21x106 CD34+ cells/2.3x105 GFP+ and 6.51x105 CD34-GFP+ cells) were injected. Long term engraftment (>30 days) was unaffected by expansion in culture. However, expanded UCB exhibited a differential pattern of homing and engraftment in comparison to unexpanded UCB. Mice receiving unexpanded UCB exhibited a strong engraftment signal from the area of the calvarium in addition to signals from other marrow spaces. The calvarium signal was only weakly and intermittently observed among mice who received the expanded UCB graft. Pathologic evaluation of these areas is in progress. CONCLUSIONS: 1. Expanded cells were capable of supporting engraftment, though at a slower rate than their unexpanded counterparts. This delay might ultimately be addressed through the optimization of the expansion technique. 2. The physiologic significance of the differential engraftment pattern(s) is unclear and will require further study. Figure Figure

scholarly journals State of the art in vivo imaging techniques for laboratory animals

2017 ◽  
Vol 51 (5) ◽  
pp. 465-478 ◽  
Author(s):  
David Tibor Lauber ◽  
András Fülöp ◽  
Tibor Kovács ◽  
Krisztián Szigeti ◽  
Domokos Máthé ◽  
...  
Keyword(s):  
Computed Tomography ◽  
In Vivo Imaging ◽  
State Of The Art ◽  
Imaging Techniques ◽  
Small Animal Imaging ◽  
Small Animal ◽  
Response To Therapy ◽  
Imaging Modalities ◽  
Animal Imaging

In recent decades, imaging devices have become indispensable tools in the basic sciences, in preclinical research and in modern drug development. The rapidly evolving high-resolution in vivo imaging technologies provide a unique opportunity for studying biological processes of living organisms in real time on a molecular level. State of the art small-animal imaging modalities provide non-invasive images rich in quantitative anatomical and functional information, which renders longitudinal studies possible allowing precise monitoring of disease progression and response to therapy in models of different diseases. The number of animals in a scientific investigation can be substantially reduced using imaging techniques, which is in full compliance with the ethical endeavours for the 3R (reduction, refinement, replacement) policies formulated by Russell and Burch; furthermore, biological variability can be alleviated, as each animal serves as its own control. The most suitable and commonly used imaging modalities for in vivo small-animal imaging are optical imaging (OI), ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI), and finally the methods of nuclear medicine: positron emission tomography (PET) and single photon emission computed tomography (SPECT).

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