Jang S.J.,Molecular Imaging Research Center |
Lee Y.J.,Molecular Imaging Research Center |
Lim S.,Korea Atomic Energy Research Institute |
Kim K.I.,Molecular Imaging Research Center |
And 8 more authors.
International Journal of Medical Microbiology | Year: 2012
The importance of noninvasive imaging methods to bacterial infections is widely recognized. To obtain bacterial infection imaging with radioisotope-labeled nucleosides, bacterial thymidine kinase (tk) activities of Salmonella typhimurium with [ 125I]5-iodo-1-(2'-fluoro-2'-deoxy-β-d-arabinofuranosyl)uracil ([ 125I]FIAU) or 3'-deoxy-3'-[ 18F]fluorothymidine ([ 18F]FLT) were measured. The infection model in BALB/c mice was imaged with [ 125I]FIAU or [ 18F]FLT using small-animal Single Photon Emission Computed Tomography (SPECT) or Positron Emission Tomography (PET), respectively.The accumulated radioactivity of [ 125I]FIAU or [ 18F]FLT in the two strains showed a linearly increased pattern with increasing incubation time or bacterial numbers. The image clearly demonstrated a high uptake of [ 125I]FIAU and [ 18F]FLT in the bacterial infection site. [ 18F]FLT uptake in the infection site of was 7.286±2.405, whereas that in the uninfected site was 0.519±0.561. The relative activity ratio of the infected region in relation to the uninfected region was 2.98 at 4h after an injection with [ 125I]FIAU determined by biodistribution data.In conclusion, the bacterial tk activity was confirmed by the cellular uptake and imaging with [ 125I]FIAU or [ 18F]FLT. Therefore, a localized bacterial infection in living mice can be monitored using radioisotope-labeled nucleosides with a nuclear medicine imaging modality. © 2012 Elsevier GmbH.
Aron Badin R.,Molecular Imaging Research Center |
Aron Badin R.,CEA Fontenay-aux-roses |
Spinnewyn B.,Ipsen |
Gaillard M.-C.,Molecular Imaging Research Center |
And 22 more authors.
PLoS ONE | Year: 2013
The development of dyskinesias following chronic L-DOPA replacement therapy remains a major problem in the long-term treatment of Parkinson's disease. This study aimed at evaluating the effect of IRC-082451 (base of BN82451), a novel multitargeting hybrid molecule, on L-DOPA-induced dyskinesias (LIDs) and hypolocomotor activity in a non-human primate model of PD. IRC-082451 displays multiple properties: it inhibits neuronal excitotoxicity (sodium channel blocker), oxidative stress (antioxidant) and neuroinflammation (cyclooxygenase inhibitor) and is endowed with mitochondrial protective properties. Animals received daily MPTP injections until stably parkinsonian. A daily treatment with increasing doses of L-DOPA was administered to parkinsonian primates until the appearance of dyskinesias. Then, different treatment regimens and doses of IRC-082451 were tested and compared to the benchmark molecule amantadine. Primates were regularly filmed and videos were analyzed with specialized software. A novel approach combining the analysis of dyskinesias and locomotor activity was used to determine efficacy. This analysis yielded the quantification of the total distance travelled and the incidence of dyskinesias in 7 different body parts. A dose-dependent efficacy of IRC-082451 against dyskinesias was observed. The 5 mg/kg dose was best at attenuating the severity of fully established LIDs. Its effect was significantly different from that of amantadine since it increased spontaneous locomotor activity while reducing LIDs. This dose was effective both acutely and in a 5-day sub-chronic treatment. Moreover, positron emission tomography scans using radiolabelled dopamine demonstrated that there was no direct interference between treatment with IRC-082451 and dopamine metabolism in the brain. Finally, post-mortem analysis indicated that this reduction in dyskinesias was associated with changes in cFOS, FosB and ARC mRNA expression levels in the putamen. The data demonstrates the antidyskinetic efficacy of IRC-082451 in a primate model of PD with motor complications and opens the way to the clinical application of this treatment for the management of LIDs. © 2013 Aron Badin et al.
Chung J.-K.,Seoul National University |
Youn H.W.,Seoul National University |
Kang J.H.,Molecular Imaging Research Center |
Lee H.Y.,Seoul National University |
Kang K.W.,Seoul National University
Nuclear Medicine and Molecular Imaging | Year: 2010
Since the specific accumulation of iodide in thyroid was found in 1915, radioiodine has been widely applied to diagnose and treat thyroid cancer. Iodide uptake occurs across the membrane of the thyroid follicular cells and cancer cells through an active transporter process mediated by the sodium iodide symporter (NIS). The NIS coding genes were cloned and identified from rat and human in 1996. Evaluation of the NIS gene and protein expression is critical in the management of thyroid cancer, and several approaches have been tried to increase NIS levels. Identification of the NIS gene has provided a means of expanding its role in the radionuclide gene therapy of nonthyroidal cancers as well as thyroid cancer. In this article, we explain the relationship between NIS expression and the treatment of thyroid carcinoma with I-131, and we include a review of the results of our experimental and clinical trials. © Korean Society of Nuclear Medicine 2010.
Mokaleng B.B.,University of Pretoria |
Ebenhan T.,University of Pretoria |
Ebenhan T.,University of South Africa |
Ramesh S.,University of South Africa |
And 8 more authors.
BioMed Research International | Year: 2015
Noninvasive imaging is a powerful tool for early diagnosis and monitoring of various disease processes, such as infections. An alarming shortage of infection-selective radiopharmaceuticals exists for overcoming the diagnostic limitations with unspecific tracers such as 67/68Ga-citrate or 18F-FDG. We report here TBIA101, an antimicrobial peptide derivative that was conjugated to DOTA and radiolabeled with 68Ga for a subsequent in vitro assessment and in vivo infection imaging using Escherichia coli-bearing mice by targeting bacterial lipopolysaccharides with PET/CT. Following DOTA-conjugation, the compound was verified for its cytotoxic and bacterial binding behaviour and compound stability, followed by 68Gallium-radiolabeling. μPET/CT using 68Ga-DOTA-TBIA101 was employed to detect muscular E. coli-infection in BALB/c mice, as warranted by the in vitro results. 68Ga-DOTA-TBIA101-PET detected E. coli-infected muscle tissue (SUV=1.3-2.4) > noninfected thighs (P=0.322) > forearm muscles (P=0.092) > background (P=0.021) in the same animal. Normalization of the infected thigh muscle to reference tissue showed a ratio of 3.0 ± 0.8 and a ratio of 2.3 ± 0.6 compared to the identical healthy tissue. The majority of the activity was cleared by renal excretion. The latter findings warrant further preclinical imaging studies of greater depth, as the DOTA-conjugation did not compromise the TBIA101's capacity as targeting vector. Copyright © 2015 Botshelo B. Mokaleng et al.
Kim J.,Kyungpook National University |
Pandya D.N.,Kyungpook National University |
Lee W.,Kyungpook National University |
Park J.W.,Kyungpook National University |
And 6 more authors.
ACS Medicinal Chemistry Letters | Year: 2014
By developing a new bimodal radioactive tracer that emits both luminescence and nuclear signals, a trimodal liposome for optical, nuclear, and magnetic resonance imaging is efficiently prepared. Fast clearance of the radiotracer from reticuloendothelial systems enables vivid tumor imaging with minimum background. © 2014 American Chemical Society.
Bel A.,Assistance Publique Hopitaux de Paris |
Borik W.,Assistance Publique Hopitaux de Paris |
Davidson S.,Royal Brompton Hospital |
Helies J.-M.,Molecular Imaging Research Center |
And 10 more authors.
European Journal of Cardio-thoracic Surgery | Year: 2016
OBJECTIVES: Heparin and protamine are standard for anticoagulation and reversal for cardiopulmonary bypass (CPB). The REGADO biosciences protocol 1 (REG1) anticoagulant system, consisting of the Factor IXa (FIXa)-inhibitor pegnivacogin and its reversal agent (anivamersen), has been studied in patients undergoing coronary catheterization and in CPB in sheep and pigs. Prior to first human use in CPB, we wanted to test the safety and efficacy of REG1 in a primate model. METHODS: Fourteen baboons undergoing 2 h of CPB followed by 1 h of reperfusion were studied. Three received heparin/protamine and 11 received 1 of 2 doses of pegnivacogin followed by anivamersen. Thrombin-generating capacity was tested in additional in vitro experiments. RESULTS: Targeted drug levels and near-complete FIXa inhibition were achieved. Bypass was run uneventfully in all animals without any clotting in the circuit and bleeding was minimal in the two groups. However, in contrast to heparin-treated baboons, those receiving pegnivacogin/anivamersen displayed thrombi in the bypass cannulae upon cannulation and kidney cortical infarcts. Inter-species comparisons revealed that in the presence of high levels of FIXa inhibition, tissue factor-mediated thrombin generation in baboons was much higher than that in other species. CONCLUSIONS: These data highlight the limitations of the baboon model for assessing factor-specific coagulation inhibitors during CPB. The justification for Phase 1 human studies using REG1 for CPB is unclear. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
Cambon K.,Molecular Imaging Research Center |
Deglon N.,University of Lausanne
Methods in Molecular Biology | Year: 2013
This chapter describes the potential use of viral-mediated gene transfer in the central nervous system for the silencing of gene expression using RNA interference in the context of Huntington's disease (HD). Protocols provided here describe the design of small interfering RNAs, their encoding in lentiviral vectors (LVs) and viral production, as well as procedures for their stereotaxic injection in the rodent brain. © Springer Science+Business Media New York 2013.
Nam W.H.,KAIST |
Ahn I.J.,KAIST |
Kim K.M.,Molecular Imaging Research Center |
Kim B.I.,Molecular Imaging Research Center |
Physics in Medicine and Biology | Year: 2013
Positron emission tomography (PET) is widely used for diagnosis and follow up assessment of radiotherapy. However, thoracic and abdominal PET suffers from false staging and incorrect quantification of the radioactive uptake of lesion(s) due to respiratory motion. Furthermore, respiratory motion-induced mismatch between a computed tomography (CT) attenuation map and PET data often leads to significant artifacts in the reconstructed PET image. To solve these problems, we propose a unified framework for respiratory-matched attenuation correction and motion compensation of respiratory-gated PET. For the attenuation correction, the proposed algorithm manipulates a 4D CT image virtually generated from two low-dose inhale and exhale CT images, rather than a real 4D CT image which significantly increases the radiation burden on a patient. It also utilizes CT-driven motion fields for motion compensation. To realize the proposed algorithm, we propose an improved region-based approach for non-rigid registration between body CT images, and we suggest a selection scheme of 3D CT images that are respiratory-matched to each respiratory-gated sinogram. In this work, the proposed algorithm was evaluated qualitatively and quantitatively by using patient datasets including lung and/or liver lesion(s). Experimental results show that the method can provide much clearer organ boundaries and more accurate lesion information than existing algorithms by utilizing two low-dose CT images. © 2013 Institute of Physics and Engineering in Medicine.
PubMed | Molecular Imaging Research Center
Type: | Journal: Methods in molecular biology (Clifton, N.J.) | Year: 2013
This chapter describes the potential use of viral-mediated gene transfer in the central nervous system for the silencing of gene expression using RNA interference in the context of Huntingtons disease (HD). Protocols provided here describe the design of small interfering RNAs, their encoding in lentiviral vectors (LVs) and viral production, as well as procedures for their stereotaxic injection in the rodent brain.
PubMed | University of Pretoria, Radiochemistry Section Necsa, North West University South Africa, University of KwaZulu - Natal and 2 more.
Type: | Journal: BioMed research international | Year: 2015
Noninvasive imaging is a powerful tool for early diagnosis and monitoring of various disease processes, such as infections. An alarming shortage of infection-selective radiopharmaceuticals exists for overcoming the diagnostic limitations with unspecific tracers such as (67/68)Ga-citrate or (18)F-FDG. We report here TBIA101, an antimicrobial peptide derivative that was conjugated to DOTA and radiolabeled with (68)Ga for a subsequent in vitro assessment and in vivo infection imaging using Escherichia coli-bearing mice by targeting bacterial lipopolysaccharides with PET/CT. Following DOTA-conjugation, the compound was verified for its cytotoxic and bacterial binding behaviour and compound stability, followed by (68)Gallium-radiolabeling. PET/CT using (68)Ga-DOTA-TBIA101 was employed to detect muscular E. coli-infection in BALB/c mice, as warranted by the in vitro results. (68)Ga-DOTA-TBIA101-PET detected E. coli-infected muscle tissue (SUV = 1.3-2.4) > noninfected thighs (P = 0.322) > forearm muscles (P = 0.092) > background (P = 0.021) in the same animal. Normalization of the infected thigh muscle to reference tissue showed a ratio of 3.0 0.8 and a ratio of 2.3 0.6 compared to the identical healthy tissue. The majority of the activity was cleared by renal excretion. The latter findings warrant further preclinical imaging studies of greater depth, as the DOTA-conjugation did not compromise the TBIA101s capacity as targeting vector.