Fluorescence-based endoscopic imaging of Thomsen–Friedenreich antigen to improve early detection of colorectal cancer

Thomsen–Friedenreich (TF) antigen belongs to the mucin-type tumor-associated carbohydrate antigen. Notably, TF antigen is overexpressed in colorectal cancer (CRC) but is rarely expressed in normal colonic tissue. Increased TF antigen expression is associated with tumor invasion and metastasis. In this study, we sought to validate a novel nanobeacon for imaging TF-associated CRC in a preclinical animal model. We developed and characterized the nanobeacon for use with fluorescence colonoscopy. In vivo imaging was performed on an orthotopic rat model of CRC. Both white light and fluorescence colonoscopy methods were utilized to establish the ratio-imaging index for the probe. The nanobeacon exhibited specificity for TF-associated cancer. Fluorescence colonoscopy using the probe can detect lesions at the stage which is not readily confirmed by conventional visualization methods. Further, the probe can report the dynamic change of TF expression as tumor regresses during chemotherapy. Data from this study suggests that fluorescence colonoscopy can improve early CRC detection. Supplemented by the established ratio-imaging index, the probe can be used not only for early detection, but also for reporting tumor response during chemotherapy. Furthermore, since the data obtained through in vivo imaging confirmed that the probe was not absorbed by the colonic mucosa, no registered toxicity is associated with this nanobeacon. Taken together, these data demonstrate the potential of this novel probe for imaging TF antigen as a biomarker for the early detection and prediction of the progression of CRC at the molecular level

Li-rod structure in high-temperature gas-cooled reactor as a tritium production device for fusion reactors

Production of tritium using a high-temperature gas-cooled reactor (HTGR) has been studied for a prior engineering test with tritium handling and for the startup operation of a demonstration fusion reactor. For this purpose, the hydrogen absorption speed of Zr in a Li-loading rod for the reactor operation is experimentally measured, and an analysis model is presented to evaluate the tritium outflow from the Li rod in a high-temperature engineering test reactor (HTTR). On the basis of the presented model, the structure of the Li-loading rod for the demonstration test using the HTTR is proposed

The T-containment properties of a Zr-containing Li rod in a high-temperature gas-cooled reactor as a T production device for fusion reactors

The production of tritium (T) using high-temperature gas-cooled reactors (HTGRs) has been studied for a prior engineering research with T handling and initial T possession in demonstration fusion reactors. Stable containment of T in Li-loading rods during HTGR operation is a critical issue. This study investigates this for an irradiation test to examine T-containment performance in Li-loading rods and develops an analytical model of evaluating the amount of T outflow to a He coolant. The hydrogen absorption characteristics, including the deterioration of the hydrogen absorption speed after Zr has sufficiently absorbed the hydrogen, is experimentally measured assuming an HTGR setting. We present an analytical model of evaluating the T outflow from a Li rod and, on the basis of this model, estimate the total T outflow, assuming the presence of a gas-turbine high-temperature reactor of 300 MWe with a nominal capacity and a high-temperature engineering test reactor. It is demonstrated that, by loading a sufficient amount of Zr into the Li rod, the T outflow can be suppressed to less than a small percent of the total T produced during 360 days of reactor operation

Biocompatible Polymers Modified with d‑Octaarginine as an Absorption Enhancer for Nasal Peptide Delivery

Peptide and protein drugs, which are categorized as biologics, exhibit poor membrane permeability. This pharmacokinetic disadvantage has largely restricted the development of noninvasive dosage forms of biologics that deliver into systemic circulation. We have been investigating the potential use of cell-penetrating peptide-linked polymers as a novel absorption enhancer to overcome this challenge. Since our previous study revealed that biocompatible poly­(<i>N</i>-vinylacetamide-<i>co</i>-acrylic acid) modified with d-octaarginine, a typical cell-penetrating peptide, enhanced in vitro permeation of biomolecules such as plasmid DNA and bovine serum albumin through cell membranes, the present study evaluated whether the polymers enhanced in vivo absorption of biologics applied on the mucosa. Mouse experiments demonstrated that d-octaarginine-linked polymers drastically enhanced nasal absorption of exendin-4, whose injection is clinically used. The mean bioavailability was 20% relative to subcutaneous administration, even though it fell short of 1% when exendin-4 alone was administered nasally. The absorption-enhancing function of the polymers was superior to that of sodium caprate and sodium <i>N</i>-(8-(2-hydroxybenzoyl)­amino) caprylate, which have been used for humans as an absorption enhancer. In vitro experiments using several biologics with different characteristics revealed that biologics interacted with d-octaarginine-linked polymers and were taken up into cells when incubated with the polymers. The interaction and cellular uptake were enhanced as molecular weights of the biologics increased; however, their charge-dependent in vitro performance was not clearly observed. The current data suggested that biologics formulated with our polymers became an alternative to their conventional invasive parenteral formulations