05-2005 Newsletter

Minnesota State University, Mankato, Library Services Newsletter for May 2005

PIXSIC: A Wireless Intracerebral Radiosensitive Probe in Freely Moving Rats

International audienceThe aim of this study was to demonstrate the potential of a wireless pixelated β+-sensitive intracerebral probe (PIXSIC) for in vivo positron emission tomographic (PET) radiopharmacology in awake and freely moving rodents. The binding of [ 11 C]raclopride to D 2 dopamine receptors was measured in anesthetized and awake rats following injection of the radiotracer. Competitive binding was assessed with a cold raclopride injection 20 minutes later. The device can accurately monitor binding of PET ligands in freely moving rodents with a high spatiotemporal resolution. Reproducible time-activity curves were obtained for pixels throughout the striatum and cerebellum. A significantly lower [ 11 C]raclopride tracer–specific binding was observed in awake animals. These first results pave the way for PET tracer pharmacokinetics measurements in freely moving rodents

Angiogenesis

APJ has been extensively described in the pathophysiology of angiogenesis and cell proliferation. The prognostic value of APJ overexpression in many diseases is now established. This study aimed to design a PET radiotracer that specifically binds to APJ. Apelin-F13A-NODAGA (AP747) was synthesized and radiolabeled with gallium-68 ([Ga]Ga-AP747). Radiolabeling purity was excellent (> 95%) and stable up to 2 h. Affinity constant of [Ga]Ga-AP747 was measured on APJ-overexpressing colon adenocarcinoma cells and was in nanomolar range. Specificity of [Ga]Ga-AP747 for APJ was evaluated in vitro by autoradiography and in vivo by small animal PET/CT in both colon adenocarcinoma mouse model and Matrigel plug mouse model. Dynamic of [Ga]Ga-AP747 PET/CT biodistributions was realized on healthy mice and pigs for two hours, and quantification of signal in organs showed a suitable pharmacokinetic profile for PET imaging, largely excreted by urinary route. Matrigel mice and hindlimb ischemic mice were submitted to a 21-day longitudinal follow-up with [Ga]Ga-AP747 and [Ga]Ga-RGD small animal PET/CT. [Ga]Ga-AP747 PET signal in Matrigel was significantly more intense than that of [Ga]Ga-RGD. Revascularization of the ischemic hind limb was followed by LASER Doppler. In the hindlimb, [Ga]Ga-AP747 PET signal was more than twice higher than that of [Ga]Ga-RGD on day 7, and significantly superior over the 21-day follow-up. A significant, positive correlation was found between the [Ga]Ga-AP747 PET signal on day 7 and late hindlimb perfusion on day 21. We developed a new PET radiotracer that specifically binds to APJ, [Ga]Ga-AP747 that showed more efficient imaging properties than the most clinically advanced tracer of angiogenesis, [Ga]Ga-RGD.France Life Imagin

Self-assembling supramolecular dendrimer nanosystem for PET imaging of tumors

Bioimaging plays an important role in cancer diagnosis and treatment. However, imaging sensitivity and specificity still constitute key challenges. Nanotechnology-based imaging is particularly promising for overcoming these limitations because nanosized imaging agents can specifically home in on tumors via the "enhanced permeation and retention" (EPR) effect, thus resulting in enhanced imaging sensitivity and specificity. Here, we report an original nanosystem for positron emission tomography (PET) imaging based on an amphiphilic dendrimer, which bears multiple PET reporting units at the terminals. This dendrimer is able to self-assemble into small and uniform nanomicelles, which accumulate in tumors for effective PET imaging. Benefiting from the combined dendrimeric multivalence and EPR-mediated passive tumor targeting, this nanosystem demonstrates superior imaging sensitivity and specificity, with up to 14-fold increased PET signal ratios compared with the clinical gold reference 2-fluorodeoxyglucose ([18F]FDG). Most importantly, this dendrimer system can detect imaging-refractory low-glucose-uptake tumors that are otherwise undetectable using [18F]FDG. In addition, it is endowed with an excellent safety profile and favorable pharmacokinetics for PET imaging. Consequently, this dendrimer nanosystem constitutes an effective and promising approach for cancer imaging. Our study also demonstrates that nanotechnology based on self-assembling dendrimers provides a fresh perspective for biomedical imaging and cancer diagnosis

Etude de transporteurs atypiques des monoamines (la familles des transporteurs de cations organiques (OCTs) et PMAT)

Les transporteurs de cations organiques (OCT) et PMAT (Plasma Membrane Monoamine Transporter) sont des transporteurs des monoamines à faible affinité. Une étude anatomique fine combinant hybridation in situ et immunohistochimie nous a permis de montrer que, dans le cerveau de rat, PMAT est exprimé principalement dans les corps cellulaires et les neurites des neurones des zones de projections des voies aminergiques, ce qui suggère un rôle dans la recapture au niveau post-synaptique. L étude anatomique d OCT2 montre que ce transporteur est fortement exprimé dans les régions limbiques. Les souris mutées pour OCT2 présentent des modifications de la neurotransmission aminergique, une réponse au stress altérée, un comportement de type dépressif , ainsi que des modifications de la sensibilité à des antidépresseurs sélectifs de la noradrénaline ou la sérotonine. Ce travail met en évidence un nouvel acteur dans les comportements liés à l humeur et la sensibilité aux antidépresseurs.PARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Estimating the change in cellular size variance during cell death using the polydisperse structure factor model

IEEE International Ultrasonics Symposium (IUS), Kobe, JAPAN, OCT 22-25, 2018International audienceQuantitative UltraSound (QUS) techniques for determining the tissue microstructure are promising tools to detect and quantify cell death, and thus monitor the tumor response to therapy. Previous in vitro experimental studies suggested that the changes in the backscatter coefficient (BSC) during cell death were linked to the increase of the cellular size variance. The aim of this work was to estimate the change in cellular size variance from the polydisperse structure factor model (SFM) by using experimental ultrasonic measurement before and after therapy. The polydisperse SFM was recently demonstrated to be efficient for explaining the measured BSCs on cell pellet biophantoms. Cell pellet biophantoms consist in centrifugated densely packed cells and serve as simplified in vitro versions of real tumors. Ultrasonic backscatter measurements were performed at frequencies ranging from 10 to 42 MHz on colon adenocarcinoma cell pellet biophantoms treated with staurosporine, a drug which induces mainly cell apoptosis. Blind estimates of QUS parameters were performed by fitting one measured BSC with a standard ultrasonic scattering model, namely the fluid sphere model (FSM). A novel approach was also proposed to estimate QUS parameters from the polydisperse SFM by using two measured BSCs before and after therapy. Finally, the relationship between the actual cellular structures and QUS parameters was investigated

Probing the cellular size distribution in cell samples undergoing cell death

International audienceA polydisperse scattering model adapted for concentrated medium, namely the polydisperse structure factor model, was examined in order to explain the backscatter coefficients (BSCs) measured from packed cell samples undergoing cell death. Cell samples were scanned using high-frequency ultrasound in the 10-42 MHz bandwidth. A parameter estimation procedure was proposed in order to estimate the volume fraction and the relative impedance contrast that could explain the changes in BSC pattern by considering the actual change in cellular size distribution. Quantitative ultrasound parameters were estimated and related to the percentage of dead cells determined by flow cytometry. The standard deviation of scatterer size distribution extracted from the polydisperse structure factor model and the spectral intercept were found to be strongly correlated to the percentage of dead cells (r^2 =0.79 and r^2 =0.72, respectively). The current study contributes to the understanding of ultrasonic scatteringfrom cells undergoing cell death toward the monitoring of cancer therapy

Estimating the change in cellular size variance during cell death using the polydisperse structure factor model

International audienceQuantitative UltraSound (QUS) techniques for determining the tissue microstructure are promising tools to detect and quantify cell death, and thus monitor the tumor response to therapy. Previous in vitro experimental studies suggested that the changes in the backscatter coefficient (BSC) during cell death were linked to the increase of the cellular size variance. The aim of this work was to estimate the change in cellular size variance from the polydisperse structure factor model (SFM) by using experimental ultrasonic measurement before and after therapy. The polydisperse SFM was recently demonstrated to be efficient for explaining the measured BSCs on cell pellet biophantoms. Cell pellet biophantoms consist in centrifugated densely packed cells and serve as simplified in vitro versions of real tumors. Ultrasonic backscatter measurements were performed at frequencies ranging from 10 to 42 MHz on colon adenocarcinoma cell pellet biophantoms treated with staurosporine, a drug which induces mainly cell apoptosis. Blind estimates of QUS parameters were performed by fitting one measured BSC with a standard ultrasonic scattering model, namely the fluid sphere model (FSM). A novel approach was also proposed to estimate QUS parameters from the polydisperse SFM by using two measured BSCs before and after therapy. Finally, the relationship between the actual cellular structures and QUS parameters was investigated

Estimating the change in cellular size variance during cell death using the polydisperse structure factor model

International audienceQuantitative UltraSound (QUS) techniques for determining the tissue microstructure are promising tools to detect and quantify cell death, and thus monitor the tumor response to therapy. Previous in vitro experimental studies suggested that the changes in the backscatter coefficient (BSC) during cell death were linked to the increase of the cellular size variance. The aim of this work was to estimate the change in cellular size variance from the polydisperse structure factor model (SFM) by using experimental ultrasonic measurement before and after therapy. The polydisperse SFM was recently demonstrated to be efficient for explaining the measured BSCs on cell pellet biophantoms. Cell pellet biophantoms consist in centrifugated densely packed cells and serve as simplified in vitro versions of real tumors. Ultrasonic backscatter measurements were performed at frequencies ranging from 10 to 42 MHz on colon adenocarcinoma cell pellet biophantoms treated with staurosporine, a drug which induces mainly cell apoptosis. Blind estimates of QUS parameters were performed by fitting one measured BSC with a standard ultrasonic scattering model, namely the fluid sphere model (FSM). A novel approach was also proposed to estimate QUS parameters from the polydisperse SFM by using two measured BSCs before and after therapy. Finally, the relationship between the actual cellular structures and QUS parameters was investigated

Altered aminergic neurotransmission in the brain of organic cation transporter 3-deficient mice

International audienceOrganic cation transporters (OCTs) are carrier-type polyspecific permeases known to participate in low-affinity extraneuronal catecholamine uptake in peripheral tissues. OCT3 is the OCT subtype most represented in the brain, yet its implication in central aminergic neurotransmission in vivo had not been directly demonstrated. In a detailed immunohistochemistry study, we show that OCT3 is expressed in aminergic pathways in the mouse brain, particularly in dopaminergic neurons of the substantia nigra compacta, non-aminergic neurons of the ventral tegmental area, substantia nigra reticulata (SNr), locus coeruleus, hippocampus and cortex. Although OCT3 was found mainly in neurons, it was also occasionally detected in astrocytes in the SNr, hippocampus and several hypothalamic nuclei. In agreement with this distribution, OCT3/Slc22a3-deficient mice show evidence of altered monoamine neurotransmission in the brain, with decreased intracellular content and increased turnover of aminergic transmitters. The behavioral characterization of these mutants reveal subtle behavioral alterations such as increased sensitivity to psychostimulants and increased levels of anxiety and stress. Altogether our data support a role of OCT3 in the homeostatic regulation of aminergic neurotransmission in the brain