Quantification of dynamic contrast-enhanced MR imaging of the knee in children with juvenile rheumatoid arthritis based on pharmacokinetic modeling

Improved management of arthritis requires a reliable, quantifiable, noninvasive method to monitor the degree of inflammation and therapeutic response during the early phase of the disease. For this purpose, the uptake of Gd-DTPA in the distal femoral physis and synovium in children with juvenile rheumatoid arthritis (JRA) was evaluated with a two-compartment pharmacokinetic model and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Employing a two-compartment pharmacokinetic model, the theoretical signal enhancement from Gd-DTPA enhanced dynamic 3D gradient-recalled echo (GRE) images was shown to have a simple linear relationship with tissue concentration independent of flip angle. The signal-enhancement patterns for each individual knee were found to be characterized by three pharmacokinetic parameters: k(ep) (min(-1)), the rate constant; k(el) (min(-1)), the elimination rate constant; and E(R) (min(-1)), the initial enhancement rate, which is proportional to the transfer constant K(trans) (min(-1)). Characteristic patterns were observed in the image signal intensity-time course. The initial enhancement rate, E(R), in regions of interest (ROIs) was found to have a wide range of variation: 5 to 38 min(-1) over the distal femoral physis and 1 to 10 min(-1) in the synovium. The E(R) of the synovium was correlated with the E(R) of the distal femoral physis (P<.05). In addition, the E(R) of the synovium was correlated to the clinical outcome measures of knee swelling. Further investigation is needed to determine whether wide variations in the pharmacokinetic parameters reflect the degree of disease activity, and whether there are changes in response to therapy. This method can also be applied in adults with rheumatoid arthritis (RA) and other disorders where T(1)-weighted contrast is used (breast cancer, brain tumors).     

Gold‐Aryl nanoparticles coated with polyelectrolytes for adsorption and protection of DNA against nuclease degradation

Binding DNA on nanoparticles was pursued to form nanoplatform for formation of non‐viral gene system. Carboxyl derivatized gold‐aryl nanoparticles can bind with biodegradable cationic polyelectrolytes such as polydiallyldimethylammonium chloride (PDADMAC). In our study, we used gold‐aryl nanoparticles (AuNPs) treated with PDADMAC to form conjugates with non‐thiol or non‐disulfide modified oligonucleotide DNA. Both AuNPs‐DNA and PDADMAC‐AuNPs‐DNA biomaterials were characterized using UV–Vis, dynamic light scattering (DLS), atomic force microscopy (AFM), transmission electron microscopy (TEM) and agarose gel electrophoresis. UV–Vis showed a red shift in the plasmon peak as compared with unconjugated AuNPs. DLS measurements also showed difference in the size of AuNPs‐DNA and PDADMAC‐AuNPs‐DNA. AFM and TEM results showed proper conjugation of DNA with AuNPs. Gel electrophoresis proved the presence of interaction between PDADMAC‐AuNPs and negatively charged DNA. The binding of DNA in the described bioconjugate enhanced its protection against nuclease degradation and prolonged its presence in the digestive environment of DNase‐I. From the results we expect that these biomaterials can be used in nanomedicine with emphasis on non‐viral gene system.