The action of acetyl-L-carnitine in dopaminergic neurotransmission

Acetyl-L-Carnitine (ALC) has been described as playing a neuroprotective effect against a variety of substances. However, the molecular mechanisms underlying its action, particularly regarding the induction of changes in neurotransmitter system, are still not fully understood. Using both a cell line and an animal model of exposure to methamphetamine (METH), we aim to contribute to clarify the mechanism by which the administration of ALC alters neurotransmitter release.info:eu-repo/semantics/publishedVersio

Usefulness of 99mTc(V)-dimercaptosuccinic acid scintigraphy in the assessment of response to external radiation therapy in soft tissue sarcoma in Giant Snauzer dog

A nine-year-old male black Giant Schnauzer dog was referred for the scintigraphic evaluation with a history of malignant fibrosarcoma with a rapidly growing non painful mass on the left shoulder region quite near to the site of an operation performed four months ago. We carried out oncological scintigraphy using pentavalent 99mTechnetium labelled dimercaptosuccinic acid [99mTc(V)-DMSA], a tumour localising radiopharmaceutical agent. The study was performed to assess the margins, vascularity of the tumour and response to the cancer therapy. Uniform intense radiopharmaceutical uptake was observed in the lesion indicating its margins, vascularity and malignant nature. The dog was subjected to external radiation therapy to control the growth of the cancer and to bring the tumour mass to an operable size. The dog was followed up with 99mTc(V)-DMSA scintigraphy pre-irradiation and post-irradiation. Immediately after the post-irradiation scintigraphy, the dog was operated on. During the surgery, resection of the tumour margins was performed carefully using a hand held gamma probe to assure that no tumour tissue was left inside. In conclusion, the authors would like to state that 99mTc(V)-DMSA oncoscintigraphy is valuable in the assessment and evaluation of therapy in canine soft tissue cancer

Preparation and in vitro stability study of 188Re-HEDP as a bone seeking radiopharmaceutical

The majority of patients with bone metastases will require some kind of therapy for bone pain palliation withtheobjective of improving the quality of live. Bone seeking radiopharmaceuticals emitting beta particles have been used for palliation of bone metastases.Recently,scientists propose a slightly different radionuclide, 188Re that showssuch promise for treating primary and metastatic tumorsas a radiopharmaceutical 188Re-HEDP.188Re-HEDP is a chemical complex of a bisphosphonate ligand with an incorporated atom of radioactive 188Re. Bisphosphonates are ligands that contain the P-C-P bond which makes the molecules resistant to breakdown by enzymatic hydrolysis and are chemically very stable.In this study, we showed the conditions for the labeling of HEDP with 188Re, and the in vitro stability of the radiopharmaceutical complex. 188Re-HEDPis intended for the treatment of patients whose condition often requiresfor the therapeutic dose to be transported to the institution where the patient is hospitalized. Our stability study is performed in order to determine the optimal storage conditions of the radiopharmaceutical if it is not applied to a patient immediately after preparation. The results of radiochemical purity of 188Re HEDP using ITLC quality control technique wasabove 98%. Thestability studyfor 188Re HEDP stored at different ambiental conditions showed that the complex is most stable in the first 3 hours after preparation, if it is stored at +4oC in the dark.It can be concluded that the prescribed preparation conditions (composition and concentration of chemical components, temperature and incubation time) are optimal for the formation of high percentageand stable initial chelating complex of 188Re-HEDP

Aluminium hydroxide stabilised MnFe2O4 and Fe3O4 nanoparticles as dual-modality contrasts agent for MRI and PET imaging

Magnetic nanoparticles (NPs) MnFe2O4 and Fe3O4 were stabilised by depositing an Al(OH)3 layer via a hydrolysis process. The particles displayed excellent colloidal stability in water and a high affinity to [18F]-fluoride and bisphosphonate groups. A high radiolabeling efficiency, 97% for 18F-fluoride and 100% for 64Cu-bisphosphonate conjugate, was achieved by simply incubating NPs with radioactivity solution at room temperature for 5min. The properties of particles were strongly dependant on the thickness and hardness of the Al(OH)3 layer which could in turn be controlled by the hydrolysis method. The application of these Al(OH)3 coated magnetic NPs in molecular imaging has been further explored. The results demonstrated that these NPs are potential candidates as dual modal probes for MR and PET. In vivo PET imaging showed a slow release of 18F from NPs, but no sign of efflux of 64Cu

Evaluation of Brain Nuclear Medicine Imaging Tracers in a Murine Model of Sepsis-Associated Encephalopathy

PURPOSE: The purpose of this study was to evaluate a set of widely used nuclear medicine imaging agents as possible methods to study the early effects of systemic inflammation on the living brain in a mouse model of sepsis-associated encephalopathy (SAE). The lipopolysaccharide (LPS)-induced murine systemic inflammation model was selected as a model of SAE. PROCEDURES: C57BL/6 mice were used. A multimodal imaging protocol was carried out on each animal 4 h following the intravenous administration of LPS using the following tracers: [(99m)Tc][2,2-dimethyl-3-[(3E)-3-oxidoiminobutan-2-yl]azanidylpropyl]-[(3E)-3-hyd roxyiminobutan-2-yl]azanide ([(99m)Tc]HMPAO) and ethyl-7-[(125)I]iodo-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carbox ylate ([(125)I]iomazenil) to measure brain perfusion and neuronal damage, respectively; 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) to measure cerebral glucose uptake. We assessed microglia activity on another group of mice using 2-[6-chloro-2-(4-[(125)I]iodophenyl)-imidazo[1,2-a]pyridin-3-yl]-N-ethyl-N-methyl -acetamide ([(125)I]CLINME). Radiotracer uptakes were measured in different brain regions and correlated. Microglia activity was also assessed using immunohistochemistry. Brain glutathione levels were measured to investigate oxidative stress. RESULTS: Significantly reduced perfusion values and significantly enhanced [(18)F]FDG and [(125)I]CLINME uptake was measured in the LPS-treated group. Following perfusion compensation, enhanced [(125)I]iomazenil uptake was measured in the LPS-treated group's hippocampus and cerebellum. In this group, both [(18)F]FDG and [(125)I]iomazenil uptake showed highly negative correlation to perfusion measured with ([(99m)Tc]HMPAO uptake in all brain regions. No significant differences were detected in brain glutathione levels between the groups. The CD45 and P2Y12 double-labeling immunohistochemistry showed widespread microglia activation in the LPS-treated group. CONCLUSIONS: Our results suggest that [(125)I]CLINME and [(99m)Tc]HMPAO SPECT can be used to detect microglia activation and brain hypoperfusion, respectively, in the early phase (4 h post injection) of systemic inflammation. We suspect that the enhancement of [(18)F]FDG and [(125)I]iomazenil uptake in the LPS-treated group does not necessarily reflect neural hypermetabolism and the lack of neuronal damage. They are most likely caused by processes emerging during neuroinflammation, e.g., microglia activation and/or immune cell infiltration

Automated material map generation from MRI scout pairs for preclinical PET attenuation correction

A novel method is presented to perform material map segmentation from preclinical MRI for corresponding PET attenuation correction. MRI does not provide attenuation ratio, hence segmenting a material map from it is challenging. Furthermore the MRI images often suffer from ghost artifacts. On the contrary MRI has no radiation dose. Our method operated with fast spin echo scout pairs that had perpendicular frequency directions. This way the direction of the ghost artifacts were perpendicular as well. Our body-air segmentation method built on this a priori information and successfully erased the ghost artifacts from the final binary mask. Visual and quantitative validation was performed by two preclinical specialists. Results indicate that our method is effective against MRI scout ghost artifacts and that PET attenuation correction based on MRI makes sense even on preclinical images

Alzheimer’s Disease: A Molecular View of β-Amyloid Induced Morbific Events

Amyloid-β (Aβ) is a dynamic peptide of Alzheimer’s disease (AD) which accelerates the disease progression. At the cell membrane and cell compartments, the amyloid precursor protein (APP) undergoes amyloidogenic cleavage by β- and γ-secretases and engenders the Aβ. In addition, externally produced Aβ gets inside the cells by receptors mediated internalization. An elevated amount of Aβ yields spontaneous aggregation which causes organelles impairment. Aβ stimulates the hyperphosphorylation of tau protein via acceleration by several kinases. Aβ travels to the mitochondria and interacts with its functional complexes, which impairs the mitochondrial function leading to the activation of apoptotic signaling cascade. Aβ disrupts the Ca2+ and protein homeostasis of the endoplasmic reticulum (ER) and Golgi complex (GC) that promotes the organelle stress and inhibits its stress recovery machinery such as unfolded protein response (UPR) and ER-associated degradation (ERAD). At lysosome, Aβ precedes autophagy dysfunction upon interacting with autophagy molecules. Interestingly, Aβ act as a transcription regulator as well as inhibits telomerase activity. Both Aβ and p-tau interaction with neuronal and glial receptors elevate the inflammatory molecules and persuade inflammation. Here, we have expounded the Aβ mediated events in the cells and its cosmopolitan role on neurodegeneration, and the current clinical status of anti-amyloid therapy

Cyclotron activated nanoparticles: application in PET/SPECT imaging

Introduction: Nanoparticles (NP) are widely used in everyday life. Pigments, cosmetic products, some foods, suncream, and many other products may contain NPs, and possible environmental pollution may be associated with wastes and NP release. Investigation of possible toxicological effects from exposure to NPs requires in vivo bio-distribution studies. Three frequently applied NPs: silver (Ag), zinc oxide (ZnO) and titanium dioxide (TiO2) were tested by our research group in activated form for quantification and tomographic detection using PET and SPECT. Materials and Methods: Activated NPs were produced in the JRC Cyclotron (Scanditronix MC40). Dry NP powders were placed in sample holders and activated for several hours by proton or deuterium irradiation. The resulting target material was left to decay for 2 weeks to allow irrelevant short-lived isotopes to decay away. Ag-105 (Ag-NP), Zn-65 (ZnO-NP) and V-48 (TiO2-NP) isotopic purity and radioactivity were determined precisely with gamma spectroscopy (Canberra GX2518 HPGe) using Genie 2000 software. The data were used to adjust quantification factors for imaging instruments NanoSPECT/CTPlus (Mediso Ltd.) and nanoScan PET/MRI (Mediso Ltd.). Using SPECT several peaks of the different gamma photon energies characteristic of the specific isotope spectra were applied. We detected 64.0, 280.5, 443.4 and 344.5 keV peaks for Ag-105, and the 560 keV peak for V-48 in addition to detecting the 511 keV annihilation peak of Zn-65 for PET. The HiSPECT (SciVis Gmbh, Germany) reconstruction algorithm was used to calculate volumes from multiplexing overlapping multi-pinhole SPECT while Tera-Tomo (Mediso Ltd) 2-D and 3-D iterative reconstruction algorithms were used to calculate PET volumes. Results: The specific activity of all the NP types used was between 1-1.5 MBq/mg. The radiation emission of Zn-65 was detected using PET, Ag-105 and V-48 were detected with both PET and SPECT. All nanoparticle samples have shown adequate signal-to-noise ratio in their spectral properties for SPECT (Ag-105, V-48) and PET (Ag-105, Zn-65 and V-48) imaging in durations between 40 minutes and 120 minutes of signal integration. Conclusion: All PET and SPECT imaging data were capable of determining the original radioactivity and distribution of the nanoparticles. Quantitation error was 24,3%. These findings provide the basis for the application of non-conventional long-lived isotope tracking of nanoparticles. The actual practicality and usefulness of the technique at realistic NP doses and at lower doses in various organs after biodistribution still has to be studied. Acknowledgement. This study was in part supported by EC-FP7 Transnational Access Facilities grant QNANO.JRC.I.4-Nanobioscience

Anticancer Potential of L-Histidine-Capped Silver Nanoparticles against Human Cervical Cancer Cells (SiHA)

This study reports the synthesis of silver nanoparticles using amino acid L-histidine as a reducing and capping agent as an eco-friendly approach. Fabricated L-histidine-capped silver nanoparticles (L-HAgNPs) were characterized by spectroscopic and microscopic studies. Spherical shaped L-HAgNPs were synthesized with a particle size of 47.43 ± 19.83 nm and zeta potential of −20.5 ± 0.95 mV. Results of the anticancer potential of L-HAgNPs showed antiproliferative effect against SiHa cells in a dose-dependent manner with an IC50 value of 18.25 ± 0.36 µg/mL. Fluorescent microscopic analysis revealed L-HAgNPs induced reactive oxygen species (ROS) mediated mitochondrial dysfunction, leading to activation of apoptotic pathway and DNA damage eventually causing cell death. To conclude, L-HAgNPs can act as promising candidates for cervical cancer therapy

A novel SPECT-based approach reveals early mechanisms of central and peripheral inflammation after cerebral ischemia.

Inflammation that develops in the brain and peripheral organs after stroke contributes profoundly to poor outcome of patients. However, mechanisms through which inflammation impacts on brain injury and overall outcome are improperly understood, in part because the earliest inflammatory events after brain injury are not revealed by current imaging tools. Here, we show that single-photon emission computed tomography (NanoSPECT/CT Plus) allows visualization of blood brain barrier (BBB) injury after experimental stroke well before changes can be detected with magnetic resonance imaging (MRI). Early 99mTc-DTPA (diethylene triamine pentaacetic acid) signal changes predict infarct development and systemic inflammation preceding experimental stroke leads to very early perfusion deficits and increased BBB injury within 2 hours after the onset of ischemia. Acute brain injury also leads to peripheral inflammation and immunosuppression, which contribute to poor outcome of stroke patients. The SPECT imaging revealed early (within 2 hours) changes in perfusion, barrier function and inflammation in the lungs and the gut after experimental stroke, with good predictive value for the development of histopathologic changes at later time points. Collectively, visualization of early inflammatory changes after stroke could open new translational research avenues to elucidate the interactions between central and peripheral inflammation and to evaluate in vivo 'multi-system' effects of putative anti-inflammatory treatments