Development of In-Labeled Monoclonal Antibodies Targeting SFTSV Structural Proteins for Molecular Imaging of SFTS Infectious Diseases by SPECT.

No effective vaccines or treatments are currently available for severe fever with thrombocytopenia syndrome (SFTS), a fatal tick-borne infectious disease caused by the SFTS virus (SFTSV). This study evaluated the potential of In-labeled anti-SFTSV antibodies targeting SFTSV structural proteins as single-photon emission computed tomography (SPECT) imaging agents for the selective visualization of SFTSV-infected sites. This study used nuclear medicine imaging to elucidate the pathology of SFTS and assess its therapeutic efficacy.

Peptide-Based Turn-On Fluorescent Probes for Highly Specific Detection of Survivin Protein in the Cancer Cells.

Survivin is highly expressed in most human cancers, making it a promising target for cancer diagnosis and treatment. In this study, we developed peptide probes consisting of Bor, a high-affinity survivin-binding peptide, and a survivin protein segment using peptide linkers as survivin-sensitive fluorescent probes (SSFPs). All conjugates were attached to 5(6)-carboxyfluorescein (FAM) at the -terminal as a fluorophore and to 4((4(dimethylamino)phenyl)azo)benzoic acid (DABCYL) at the -terminal as a quencher.

Borealin-Derived Peptides as Survivin-Targeting Cancer Imaging and Therapeutic Agents.

Survivin is overexpressed in most cancer cells but is rarely expressed in normal adult tissues. It is associated with poor prognosis and resistance to radiation therapy and chemotherapy. In this study, we designed and synthesized borealin-derived small peptides (Bor peptides) to function as survivin-targeting agents for the diagnosis and treatment of cancers.

Synthesis and Biological Evaluation of Novel 2-(Benzofuran-2-yl)-chromone Derivatives for In Vivo Imaging of Prion Deposits in the Brain.

Prion diseases are fatal neurodegenerative disorders caused by the deposition of scrapie prion protein aggregates (PrP) in the brain. We previously reported that styrylchromone (SC) and benzofuran (BF) derivatives have potential as imaging probes for PrP. To further improve their properties, we designed and synthesized 2-(benzofuran-2-yl)-chromone (BFC) derivatives hybridized with SC and BF backbones as novel single-photon emission computed tomography probes for the detection of cerebral PrP deposits.

Identification and removal of aflatoxin coprecipitates derived from plant samples on immunoaffinity chromatographic purification.

The non-polar compounds that coprecipitate with aflatoxins and interfere aflatoxin analysis using an immunoaffinity column (IAC) were identified and an effective pretreatment method was developed in combination with IAC. The proanthocyanidins fractionated from cinnamon coprecipitated with four major aflatoxins (B, G, B and G) and were effectively removed using zirconia-coated silica gel. A pretreatment method which combined zirconia-coated silica gel and an IAC was developed for LC-MS/MS analysis of aflatoxins and the combined method substantially improved the recovery of the analytes.

Synthesis and Characterization of Hydroxyethylamino- and Pyridyl-Substituted 2-Vinyl Chromone Derivatives for Detection of Cerebral Abnormal Prion Protein Deposits.

Prion diseases are fatal neurodegenerative diseases characterized by the deposition of abnormal prion protein aggregates (PrP) in the brain. In this study, we developed hydroxyethylamino-substituted styrylchromone (SC) and 2-(2-(pyridin-3-yl)vinyl)-4H-chromen-4-one (VPC) derivatives for single-photon emission computed tomography (SPECT) imaging of PrP deposits in the brain. The binding affinity of these compounds was evaluated using recombinant mouse prion protein (rMoPrP) aggregates, which resulted in the inhibition constant (K) value of 61.

Peptidyl-prolyl cis-trans isomerase A participates in the selenium transport into the rat brain.

Selenium, an essential micronutrient, plays vital roles in the brain. Selenoprotein P (SELENOP), a major plasma selenoprotein, is thought to transport selenium to the brain. However, Selenop-knockout mice fed a diet containing an adequate amount of selenium shows no objective neurological dysfunction which is observed in the selenium-deficient diet-fed Selenop-knockout mice.

Synthesis and Characterization of Radiogallium-Labeled Cationic Amphiphilic Peptides as Tumor Imaging Agents.

SVS-1 is a cationic amphiphilic peptide (CAP) that exhibits a preferential cytotoxicity towards cancer cells over normal cells. In this study, we developed radiogallium-labeled SVS-1 (Ga-NOTA-KV6), as well as two SVS-1 derivatives, with the repeating KV residues replaced by RV or HV (Ga-NOTA-RV6 and Ga-NOTA-HV6). All three peptides showed high accumulation in epidermoid carcinoma KB cells (53-143% uptake/mg protein).

Feasibility studies of radioiodinated pyridyl benzofuran derivatives as potential SPECT imaging agents for prion deposits in the brain.

Introduction: Prion diseases are fatal neurodegenerative disorders caused by the deposition of abnormal prion protein aggregates (PrP) in the central nervous system. This study aimed to evaluate the use of iodinated pyridyl benzofuran (IPBF) derivatives as single-photon emission computed tomography (SPECT) probes for the detection of cerebral PrP deposits.

Methods: In vitro binding assays of IPBF derivatives were carried out in the recombinant mouse prion protein (rMoPrP) and brain sections of mouse-adapted bovine spongiform encephalopathy (mBSE)-infected mice.

Discovery of inner centromere protein-derived small peptides for cancer imaging and treatment targeting survivin.

Survivin belongs to the inhibitor of apoptosis protein family, which is consistently overexpressed in most cancer cells but rarely expressed in normal adult tissues. Therefore, the detection and inhibition of survivin are regarded as attractive strategies for cancer-specific treatment. In this study, we designed and synthesized 7-19 residues of inner centromere protein (INCENP)-derived small peptides (INC peptides) as novel survivin-targeting agents.

Synthesis and evaluation of radioactive/fluorescent peptide probes for imaging of legumain activity.

Legumain or asparaginyl endopeptidase is an enzyme overexpressed in some cancers and involved in cancer migration, invasion, and metastasis. We have developed radioiodine- ([I]I-LCP) or fluorescein-labeled peptides (FL-LCP) with a cell-permeable d-Arg nonamer fused to an anionic d-Glu nonamer via a legumain-cleavable linker, to function as peptide probes that measure and monitor legumain activity. Non-cleavable probes of FL-NCP and [I]I-NCP were similarly prepared and evaluated as negative control probes by altering their non-cleavable sequence.

Development of Radioiodinated Benzofuran Derivatives for Imaging of Prion Deposits in the Brain.

Prion diseases are fatal neurodegenerative disorders associated with the deposition of abnormal prion protein aggregates (PrP) in the brain tissue. Here, we report the development of I-labeled iodobenzofuran (IBF) derivatives as single photon emission computed tomography (SPECT) imaging probes to detect cerebral PrP deposits. We synthesized and radioiodinated several 5-IBF and 6-IBF derivatives.

In vitro assessment of bioavailability of selenium from a processed Japanese anchovy, Niboshi.

Niboshi is a commonly used foodstuff that is processed from Japanese anchovy (Engraulis japonicus) in Japanese cuisine. It was previously demonstrated that Niboshi and its water extract contained highly bioavailable selenium for selenium deficient mice. In this study, we assessed the selenium bioavailability from the extract of the Niboshi, using cultured cells.

Synthesis and characterization of radioiodinated 3-phenethyl-2-indolinone derivatives for SPECT imaging of survivin in tumors.

Survivin, overexpressed in most cancers, is associated with poor prognosis and resistance to radiation therapy and chemotherapy. Herein, we report the synthesis of three 3-phenethyl-2-indolinone derivatives and their application as in vivo imaging agents for survivin. Of these, 3-(2-(benzo[d][1,3]dioxol-5-yl)-2-oxoethyl)-3-hydroxy-5- iodoindolin-2-one (IPI-1) showed the highest binding affinity (K = 68.

Cardiac myoglobin participates in the metabolic pathway of selenium in rats.

As an essential micronutrient, selenium deficiency is a leading cause of cardiovascular diseases. The heart is continuously beating to deliver blood to the entire body, and this requires a high amount of energy. An adult heart normally obtains 50-70% of its adenosine 5'-triphosphate from fatty acid β-oxidation.

Selenoprotein L-inspired nano-vesicular peroxidase mimics based on amphiphilic diselenides.

In this study, we developed selenoprotein L-inspired nano-vesicular peroxidase mimics based on amphiphilic diselenides. Selenocystine (SeCyst) was used as the starting material for the synthesis of four liposomal membrane-compatible diselenide derivatives (R-Se-Se-R') with two hydrophobic tails and a polar part. The diselenide derivatives were successfully incorporated into the phosphatidylcholine (PC)-based nano-vesicular scaffold.

Characterization of Selenium Species in the Shijimi Clam.

Selenium is an essential trace element for humans and animals. Fish and shellfish are known to be rich in selenium and suppose to be an effective selenium source. In this study, we characterized the selenium species in the Shijimi clam (Corbicula japonica), which is a typical clam eaten in Japan.

Development of a Ge/Ga Generator System Using Polysaccharide Polymers and Its Application in PET Imaging of Tropical Infectious Diseases.

Gallium-68 (Ga) is a positron emitter for clinical positron emission tomography (PET) applications that can be produced by a Ge/Ga generator without cyclotron. However, commercially available Ge/Ga generator systems require multiple steps for the preparation of Ga radiopharmaceuticals and are sometimes plagued by metallic impurities in the Ga eluent. We developed a Ge/Ga generator system using polysaccharide-based adsorbents and direct application of the generator-eluted Ga-citrate to PET imaging of tropical infectious diseases.

Development of radioiodinated acridine derivatives for in vivo imaging of prion deposits in the brain.

Prion diseases are caused by deposition of abnormal prion protein aggregates (PrP) in the central nervous system. This study aimed to develop in vivo imaging probes that can detect cerebral PrP deposits. We synthesized several quinacrine-based acridine (AC) derivatives with 2,9-substitution and radioiodinated them.

Amyloid formation characteristics of GNNQQNY from yeast prion protein Sup35 and its seeding with heterogeneous polypeptides.

Sup35 is a prion-like protein from yeast and shares the ability to transmit its aberrant fold and to aggregate into amyloid fibrils. GNNQQNY from the prion-determining domain of Sup35 was reported to form an amyloid. We first investigated the self-aggregation transition behavior of GNNQQNY to the β-sheet amyloid state under various conditions.

Synthesis of Nanovesicular Glutathione Peroxidase Mimics with a Selenenylsulfide-Bearing Lipid.

In this article, we describe the development of a nanosized-glutathione peroxidase (GPx) mimic based on liposomes of which the amphiphilic selenenylsulfide derivative (R-Se-S-R') was incorporated into a lipid membrane. A lipid membrane-compatible selenenylsulfide derivative, 1-oxo-headecyl-seleno-l-cysteine-methyl--yl--l-penicillamine methyl ester (OHSeP), was synthesized. X-ray photoelectron spectroscopy revealed that the sulfur and selenium atoms of the OHSeP molecule formed a selenenylsulfide linkage.

Synthesis and evaluation of a radioiodinated 4,6-diaryl-3-cyano-2-pyridinone derivative as a survivin targeting SPECT probe for tumor imaging.

Survivin is overexpressed in most of the cancerous tissues but not in terminally differentiated normal tissues, making it an attractive target for diagnosis and therapy of various types of cancers. In this study, we aimed to develop 4,6-diaryl-3-cyano-2-pyridinone (DCP) derivatives, as novel cancer imaging probes that target survivin. Chloro and iodo analogs of DCP (CDCP and IDCP, respectively) were successfully synthesized by using a previously unreported carbon monoxide-free procedure.

A Comprehensive Analysis of Selenium-Binding Proteins in the Brain Using Its Reactive Metabolite.

The intracellular metabolism of selenium in the brain currently remains unknown, although the antioxidant activity of this element is widely acknowledged to be important in maintaining brain functions. In this study, a comprehensive method for identifying the selenium-binding proteins using PenSSeSPen as a model of the selenium metabolite, selenotrisulfide (RSSeSR, STS), was applied to a complex cell lysate generated from the rat brain. Most of the selenium from L-penicillamine selenotrisulfide (PenSSeSPen) was captured by the cytosolic protein thiols in the form of STS through the thiol-exchange reaction (R-SH+PenSSeSPen→R-SSeSPen+PenSH).

Characterisation of radioiodinated flavonoid derivatives for SPECT imaging of cerebral prion deposits.

Prion diseases are fatal neurodegenerative diseases characterised by deposition of amyloid plaques containing abnormal prion protein aggregates (PrP(Sc)). This study aimed to evaluate the potential of radioiodinated flavonoid derivatives for single photon emission computed tomography (SPECT) imaging of PrP(Sc). In vitro binding assays using recombinant mouse PrP (rMoPrP) aggregates revealed that the 4-dimethylamino-substituted styrylchromone derivative (SC-NMe2) had higher in vitro binding affinity (Kd = 24.