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Organ Distribution (organ + distribution)
Selected AbstractsIn vivo magnetic resonance imaging of iron oxide,labeled, arterially-injected mesenchymal stem cells in kidneys of rats with acute ischemic kidney injury: Detection and monitoring at 3TJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 6 2007Harald Ittrich MD Abstract Purpose To evaluate MRI for a qualitative and quantitative in vivo tracking of intraaortal injected iron oxide,labeled mesenchymal stem cells (MSC) into rats with acute kidney injury (AKI). Materials and Methods In vitro MRI and R2* measurement of nonlabeled and superparamagnetic iron oxide (SPIO)-labeled MSC (MSCSPIO) was performed in correlation to cellular iron content and cytological examination (Prussian blue, electron microscopy). In vivo MRI and R2* evaluation were performed before and after ischemic/reperfusion AKI (N = 14) and intraaortal injection of 1.5 × 106 MSCSPIO (N = 7), fetal calf serum (FCS) (medium, N = 6), and SPIO alone (N = 1) up to 14 days using a clinical 3T scanner. Signal to noise ratios (SNR), R2* of kidneys, liver, spleen, and bone marrow, renal function (creatinine [CREA], blood urea nitrogen [BUN]), and kidney volume were measured and tested for statistical significance (Student's t -test, P < 0.05) in comparison histology (hematoxylin and eosin [H&E], Prussian blue, periodic acid-Schiff [PAS], CD68). Results In vitro, MSCSPIO showed a reduction of SNR and T2* with R2* , number of MSCSPIO (R2 = 0.98). In vivo MSCSPIO administration resulted in a SNR decrease (35 ± 15%) and R2* increase (101 ± 18.3%) in renal cortex caused by MSCSPIO accumulation in contrast to control animals (P < 0.01). Liver, spleen, and bone marrow (MSCSPIO) showed a delayed SNR decline/R2* increase (P < 0.05) resulting from MSCSPIO migration. The increase of kidney volume and the decrease in renal function (P < 0.05) was reduced in MSC-treated animals. Conclusion Qualitative and quantitative in vivo cell-tracking and monitoring of organ distribution of intraaortal injected MSCSPIO in AKI is feasible in MRI at 3T. J. Magn. Reson. Imaging 2007;25:1179,1191. © 2007 Wiley-Liss, Inc. [source] Evaluation of hepatotropic targeting properties of allogenic and xenogenic erythrocyte ghosts in normal and liver-injured ratsLIVER INTERNATIONAL, Issue 2 2008Olav A. Gressner Abstract Background/Aims: Haemoglobin-depleted erythrocyte ghosts have been recommended as vesicle carriers of drugs with hepatotropic properties. However, the influence of liver injury on ghost elimination and targeting has not been reported so far. Methods: Human and rat ghosts were prepared and loaded with model substances, and the basic parameters were characterized. Ghosts were injected intravenously into rats with acute, subacute and chronic liver injuries. Elimination from circulation, organ distribution and cellular targeting was measured. The uptake of ghosts by liver macrophages/Kupffer cells was determined in cell culture. Results: Ghosts are strong hepatotropic carriers with a recovery of 90% in normal liver. Kupffer cells are the almost exclusive target cell type. Hepatotropic properties remain in rats with chronic liver diseases, but are reduced by 60,70% in acute liver damage as a result of decline of phagocytosis of macrophages/Kupffer cells. Although the uptake of ghosts per gram liver tissue in chronic liver injury was also reduced by about 40%, the increase of liver mass and of macrophages/Kupffer cells compensated for the reduced phagocytotic activity. In subacute injury, the uptake per gram liver tissue was only moderately reduced. Conclusion: Drug targeting with ghosts might be feasible in chronic and subacute liver injuries, e.g. fibrogenesis and tumours, because the content of ingested ghosts is released by Kupffer cells into the micro-environment, providing the uptake by and pharmacological effects on adjacent cells. [source] Biodegradable comb polyesters containing polyelectrolyte backbones facilitate the preparation of nanoparticles with defined surface structure and bioadhesive properties,POLYMERS FOR ADVANCED TECHNOLOGIES, Issue 10-12 2002A. Breitenbach Abstract A major challenge in oral peptide and protein delivery remains the search for suitable carrier systems. Therefore, a new concept was investigated combining a modified three-dimensional architecture, increased hydrophilicity of poly(lactic- co -glycolic acid) (PLGA) and charged groups in a single polymer. Biodegradable comb PLGA were synthesized by grafting short PLGA chains onto different poly(vinyl alcohol) (PVA) based backbone polyols, poly(2-sulfobutyl-vinyl alcohol) and poly(diethylaminoethyl-vinyl alcohol). The polyelectrolyte backbones were obtained by etherification of PVA with charge-containing pendent groups. The comb polymer structure could be confirmed by nuclear magnetic resonance, infrared spectroscopy, differential scanning calorimetry, elemental analysis and measurement of intrinsic viscosity. Nanoparticles (NP), as potential mucosal carriers systems, were prepared by controlled precipitation and investigated as a function of polymer composition. The amphiphilic character and the three-dimensional architecture of the novel polyesters allowed the preparation of small nanoparticles even without the use of surfactants. Surface NMR, surface charge and hydrophobicity determination indicate a core,corona-like NP structure, especially in the case of negatively charged polyesters. A structural model is proposed for the NP with an inner polyester core and an outer charged-groups-containing surface, depending on polymer composition and backbone charge density. The higher the polymer backbone charge density, the more pronounced its influence on the nanoparticle surface properties. The possibility of preparing NP without the use of a surfactant, as well as of designing the NP surface characteristics by polymer backbone charge density and polymer hydrophilic,hydrophobic balance, will be a major advantage in protein adsorption, bioadhesion and organ distribution. This makes these biodegradable polymers promising candidates for colloidal protein and peptide delivery. Copyright © 2003 John Wiley & Sons, Ltd. [source] Pretargeted radioimmunoscintigraphy in patients with primary colorectal cancer using a bispecific anticarcinoembryonic antigen CEA X anti-di-diethylenetriaminepentaacetic acid F(ab,)2 antibody,,CANCER, Issue S4 2010Frits Aarts PhD Abstract BACKGROUND: Antibody-based imaging agents are available commercially, but their success has been limited, mainly because of low contrast and the emergence of 2-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) scanning. In pretargeting, administration of the radionuclide is separated from the antibody, thereby enhancing image contrast and allowing detection at earlier time points after injection. METHODS: The authors conducted an open-label, single-arm trial that assessed a pretargeting procedure in which an anticarcinoembryonic antigen x (anti-CEA x) anti-diethylenetriaminepentaacetic acid (anti-DTPA)-indum (In) antibody was used in combination with a 111In-labeled di-DTPA peptide for the diagnostic imaging of CEA-expressing colorectal cancer. Three patients received the 111In peptide alone to investigate tumor targeting, organ distribution, and clearance of the peptide. Thereafter, 11 patients received the bispecific antibody (bsAb) (5 mg) to pretarget the tumor. After 3 to 5 days, patients were injected with 185 megabecquerels of 111In-labeled peptide to assess the optimal interval for best image quality. RESULTS: Fourteen patients with primary colorectal cancer were enrolled. One of 3 patients who received 111In peptide alone had low-level tumor uptake. In 9 of 11 other patients, tumors were observed. In 1 patient, FDG-PET,positive lymph nodes were observed clearly with pretargeted immunoscintigraphy. Peptide pharmacokinetics revealed enhanced circulating levels of 111In-labeled peptide in patients in the 3-day interval cohort compared with the other cohorts. Tumor-to-background ratios ranged from 3.5 to 6.4 in the 3-day interval group, from 5.1 to 14.2 in the 4-day interval group, and from 3.5 to 3.9 in the 5-day interval group. The best images were acquired with a 4-day interval at 24 hours after injection of the radiolabeled peptide. Grade 1 adverse events were observed in 2 patients. CONCLUSIONS: Imaging of colorectal cancer using a 2-step, pretargeting system produced the best imaging results 24 hours after peptide administration using a 4-day interval between injection of the bsAb and the peptide. Cancer 2010;116(4 suppl):1111,7. © 2010 American Cancer Society. [source] Gastrointestinal persorption and tissue distribution of differently sized colloidal gold nanoparticlesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 12 2001Julián F. Hillyer Abstract The gastrointestinal uptake of micro- and nanoparticles has been the subject of recent efforts to develop effective carriers that enhance the oral uptake of drugs and vaccines. Here, we used correlative instrumental neutron activation analysis and electron microscopy to quantitatively and qualitatively study the gastrointestinal uptake and subsequent tissue/organ distribution of 4, 10, 28, and 58 nm diameter metallic colloidal gold particles following oral administration to mice. In our quantitative studies we found that colloidal gold uptake is dependent on particle size: smaller particles cross the gastrointestinal tract more readily. Electron microscopic studies showed that particle uptake occurred in the small intestine by persorption through single, degrading enterocytes in the process of being extruded from a villus. To our knowledge this is the first report, at the ultrastructural level, of gastrointestinal uptake of particulates by persorption through holes created by extruding enterocytes. © 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:1927,1936, 2001 [source] | ||||||||||