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Transferrin receptor (TfR) is highly expressed on rapidly dividing inflammatory cells, but not in nonproliferating cells. We investigated whether scintigraphic imaging using 99mTechnetium-radiolabeled transferrin (99mTc-Tf) is useful for early detection of synovial inflammation of collagen-induced arthritis (CIA) mouse. 99mTc-Tf conjugate was synthesized to target the TfR in inflamed synovium. 99mTc-Tf scintigraphic images were obtained in nonarthritic normal mouse and advanced phase of CIA mouse. 99mTc-Tf and 99mTc-methylenediphosphonate (99mTc-MDP) bone scintigraphic images were obtained in same early phase of CIA mouse. Western blot analysis, hematoxylin & eosin (H&E), and immunohistochemical staining were performed to determine development of arthritis and expression of TfR. Image analyses revealed that the uptake of 99mTc-Tf in inflamed joints of advanced phase of CIA mouse was markedly higher than those by normal nonarthritic mouse. 99mTc-Tf scintigraphy also showed higher uptake in knee joint prior to significant joint swelling in early phase of CIA mouse but 99mTc-MDP bone scintigraphy does not. These scintigraphic findings are well correlated with the results of Western blot, H&E and immunohistochemical analysis. In conclusion, TfR can be used as a specific target for molecular imaging in CIA mouse, and 99mTc-Tf scintigraphy detects synovial inflammation prior to significant clinical findings in CIA mouse.

Transferrin is one of acute phase reactants in inflamed lesion. Expression of transferrin receptor is increased in activated macrophage during inflammation process. Conjugates of target ligand with novel water-soluble chitosan for fast excretion of background radioactivity have been shown to be selectively taken up via the target molecules. In this study, radiolabeled 99m Tc-Transferrin conjugate was synthesized and evaluated its efficacy in vivo as a targeted agent for the rapid detection of inflamed lesion that expresses relatively high level of transferrin receptors. Transferrin was conjugated with HYNIC-chitosan and radiolabeled with 99m Tc. The biodistribution and scintigraphic images with the 99m Tc-HYNIC-chitosan-Transferrin conjugate (99m Tc-Tfc) were studied in a murine infection model in which the infection was induced with Escherichia coli (2 x 10(6) colonies). The %ID/g was as follows: 1.612 +/- 0.098, 2.473 +/- 0.202 and 2.617 +/- 0.646% at 30, 120 min and 6 h after injection, respectively. Gamma camera imaging rapidly visualized the infection/inflammation lesion, with the lesion-to-background ratio improving with time up to 5.68 +/- 0.48. 99m Tc-Tfc scintigraphy allows rapid and good imaging of an inflamed lesion.

Our goal is to develop the functionalized superparamagnetic iron oxide nanoparticles (SPIONs) demonstrating the capacities to be delivered in liver specifically and to be dispersed in physiological environment stably. For this purpose, SPIONs were coated with polyvinylbenzyl-O-β-D-galactopyranosyl-D-gluconamide (PVLA) having galactose moieties to be recognized by asialoglycoprotein receptors (ASGP-R) on hepatocytes. For use as a control, we also prepared SPIONs coordinated with 2-pyrrolidone. The sizes, size distribution, structure, and coating of the nanoparticles were characterized by transmission electron microscopy (TEM), electrophoretic light scattering spectrophotometer (ELS), X-ray diffractometer (XRD), and Fourier transform infrared (FT-IR), respectively. Intracellular uptake of the PVLA-coated SPIONs was visualized by confocal laser scanning microscopy, and their hepatocyte-specific delivery was also investigated through magnetic resonance (MR) images of rat liver. MRI experimental results indicated that the PVLA-coated SPIONs possess the more specific accumulation property in liver compared with control, which suggests their potential utility as liver-targeting MRI contrast agent.

A self-assembled multilayer (SAMu) including the alginate layer was prepared for detecting Pseudomonas aeruginosa cells in a solution and its potential was evaluated with a BIAcore system. After layer-by-layer formation, the refractive units (RU) values monitored with the biosensor increased by the interaction between the layers. The responses by the binding of P. aeruginosa cells to the alginate-immobilized SAMu were visualized immediately upon injection of the cell suspension. The RU values after injection of the cells were measured with approximately 1152, 656 and 173 for 1 × 109, 1 × 108 and 1 × 107 CFU/ml. This result suggests that the alginate-immobilized SAMu will have useful application for detecting P. aeruginosa cells in a biosensor analysis.

Hydrocortisone (HC)-loaded rosin nanoparticles were prepared by a dispersion and dialysis method without addition of surfactant. They were spherical: 167-332 nm diam. The drug was loaded approximately 50% of initial feeding amount in all formulation. Release of hydrocortisone from the nanoparticles in vitro gradually decreased with increasing initial rosin content at pH 7.4. HC was also released very slowly at pH 1.2. Nanoparticles based on rosin thus are potentially useful as a drug delivery system.

Background and Objectives: Reperfusion of ischemic myocardium is necessary to salvage tissue from eventual death. However, new pathophysiological changes are initiated after reperfusion. The aim of this study was to investigate one of the mechanisms of ischemia/reperfusion (I/R) injury, and we focused on transferrin. Materials and Methods: Male Spragre-Dawley (SD) rats were used for the I/R model. Myocardial ischemia was produced by occlusion of the left anterior descending coronary artery for 30 minutes. Tc Transferrin-Chitosan-hydrazino nicotinate hydrochloride (HYNIC) (Tfc) (≒37 MBq/mL) was injected once after the reperfusion was finished. Autoradiography, hematoxylin and eosin (H & E) staining and determination of the tissue myeloperoxidase (MPO) activity were performed. Results: Autoradiography showed remarkable Tc-Tfc uptake in the left ventricular myocardium at the reperfusion period from 0 to 1.5 hours, whereas no uptake was demonstrated at 3 hours. The uptake was increased again at 6 and 24 hours. Western blotting showed that the transferrin receptor (TfR) proteins were increased at 0 to 1.5 hours compared with that of the control; this expression of TfR disappeared at 3 hours, and it showed up for the second time at 6 and 24 hours. The MPO activity only at 24 hours was significantly higher than that of the control and those MPO activities at 0 to 6 hours (p=0.001). Conclusion: In the rodent model of 30 minutes occlusion and reperfusion, our study revealed, with using Tc-Tfc, that the TfR expression increased in the myocardium till 3 hours after reperfusion. TfR-mediated entry of iron into the cardiomyocytes may represent that this process plays a role in the I/R injury during the early reperfusion period. (Korean Circ J 2008;38:360-365)

The aim of this study was to ascertain the folate receptor (FR) targetability by an in vitro study and to acquire FR-targeted images in vivo models by using synthetic folate conjugates. PEG-folate was synthesized and labeled with (99m)Tc and fluorescein isothiocynate (FITC). Cell uptake studies were carried out in KB cells (FR-positive) and A549 cells (FR-negative) using FITC- and the (99m)Tc-labeled conjugates. The radiolabeled conjugate was intravenously injected to KB tumor xenografted mice. After it was injected, gamma images were recorded at 30 min, 1, 2, 3 and 4 hr. Cell uptake studies showed a difference between the KB cells and the A549 cells by flow cytometry analysis and gamma counting. On in vivo images, the tumor-to-normal muscle ratio was greater than 4. It ascertained that the PEG-folate conjugate specifically binds to the FR expressed on tumor cells in vitro. Moreover, it was possible to acquire the FR-targeted gamma images using PEG-folate conjugates in tumor models.