Pulsed nuclear magnetic resonance studies were carried out on small ice particles with large surface to volume ratios to investigate the so-called quasi-liquid layer (Q.L.L.) on an ice surface. The temperature dependence of features of the NMR spectra and dynamical properties such as the correlation the for rotational motion and the self diffusion coefficient of the Q.L.L. were described. The frequency of the rotational molecular motion and the self diffusion coefficient were larger than those of bulk ice by about five orders and by two orders, respectively
Metallic radionuclides provide target-specific radiolabeled probes for molecular imaging in radiochemical yields sufficient for administration to subjects without purification. However, unlabeled ligands in the injectate can compete for targeted molecules with radiolabeled probes, which eventually necessitates postlabeling purification. Herein we describe a "1 to 3" design to circumvent the issue by taking advantage of inherent coordination properties of technetium-99m ((99m)Tc). A monovalent RGD ligand possessing an isonitrile as a coordinating moiety (CN-RGD) was reacted with [(99m)Tc(CO)3(OH2)3](+) to prepare [(99m)Tc(CO)3(CN-RGD)3](+) in over 95% radiochemical yields. This complex exhibited higher integrin αvβ3 binding affinity than its unlabeled monovalent ligand, primarily due to its multivalency. This compound visualized a murine tumor without removing unlabeled ligands, while a (99m)Tc-labeled monovalent probe derived from a monovalent ligand could not. The metal coordination-mediated synthesis of radiolabeled multivalent probes thereby can be a useful approach for preparing ready-to-use target-specific probes labeled with (99m)Tc and other metallic radionuclides of interest.
The performance of hepatitis B surface antigen (HBsAg) screening assays is continuously improved to reduce the risk of transfusion-associated hepatitis B. In this study, a semiautomated immune complex transfer chemiluminescence enzyme immunoassay (ICT-CLEIA) for the detection of HBsAg, which is as sensitive as hepatitis B virus (HBV) DNA PCR, was developed; the ICT-CLEIA assay performance was compared with the performance of the Architect HBsAg QT assay and HBV DNA PCR. The specificities in the initial assay and after retesting were 99.50% (1,988/1,998 samples) and 99.95% (1,997/1,998 samples), respectively. The analytical detection limit was determined to be 0.2 mIU/ml using the 2nd International WHO HBsAg standard, and the cutoff value (0.5 mIU/ml) of the ICT-CLEIA assay was 8.0 standard deviations (SD) above the mean of the HBsAg-negative specimens. The ICT-CLEIA assay could detect HBsAg even in the presence of anti-HBs antibodies and demonstrated a 23.6-dayshorter window period using commercially available HBsAg seroconversion panels than the Architect HBsAg QT assay. Furthermore, the monitoring of the viral kinetics by the ICT-CLEIA assay and the HBV DNA PCR produced very similarly shaped curves during both the HBsAg seroconversion and reverse seroconversion periods. Therefore, the ICT-CLEIA assay may be useful not only for an earlier detection of HBV reactivation but also for the monitoring of hepatitis B patients.
In the synthesis of technetium-99m (Tc) labeled target-specific ligands, the presence of a large excess of unlabeled ligands over Tc in the injectate hinders target accumulation ofTc-labeled ligands by competing for target molecules. To circumvent the problem, we recently developed a concept of the metal coordination-mediated multivalency, and proved the concept with a Tc-labeled trivalent compound [Tc(CO)(CN-RGD)]. In this study, D-penicillamine (Pen) was selected as a chelating molecule and a cyclic RGDfK peptide was conjugated to Pen via a hexanoic linkage (Pen-Ahx-c(RGDfK)). Tc complexation reaction, and the stability, integrin αβ binding affinity, and biodistribution of the Tc-labeled probe were investigated to evaluate the applicability of the concept to bivalent probes.Tc-[Pen-Ahx-c(RGDfK)] was obtained over 95% radiochemical yields under low Pen-Ahx-c(RGDfK) concentration (50 μM). Tc-[Pen-Ahx-c(RGDfK)] showed approximately 10-times higher integrin αβ binding affinity than the monovalent compounds, Pen-Ahx-c(RGDfK) and c(RGDyV). In biodistribution studies, the tumor accumulation of Tc-[Pen-Ahx-c(RGDfK)] was decreased to 77% and 43% of HPLC-purified (Pen-Ahx-c(RGDfK)-free) Tc-[Pen-Ahx-c(RGDfK)] by the presence of 5 nmol of unlabeled Pen-Ahx-c(RGDfK) and Re-[Pen-Ahx-c(RGDfK)], respectively. Tc-[Pen-Ahx-c(RGDfK)] provided tumor image without removing unlabeled ligand, while a Tc-labeled monovalent probe prepared from a monovalent ligand could not. These findings indicate the availability of the design concept to prepareTc-labeled bivalent probes with a variety of Tc core and other metallic radionuclides of clinical relevance.
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