An At-labeled alpha-melanocyte stimulating hormone peptide analog for targeted alpha therapy of metastatic melanoma.

Purpose: Patients who develop metastatic melanoma have a very poor prognosis, and new treatments are needed to improve the response rates. Melanocortin-1 receptor (MC1R) is a promising target for radionuclide therapy of metastatic melanoma, and alpha-melanocyte stimulating hormone (α-MSH) peptide analogs show high affinities to MC1Rs. Because targeted alpha therapy (TAT) can be a desirable treatment for metastatic melanoma, this study aimed to develop an At-labeled α-MSH peptide analog for TAT of metastatic melanoma.

Asymmetric Atomic Coordination of Platinum Skin Layer on Intermetallic Platinum-Cobalt Particles.

Pt-based intermetallic alloy particles with a Pt skin layer have higher catalytic activity than solid-solution alloy particles and have attracted considerable attention for practical applications in polymer electrolyte fuel cells. However, the reason for the superior performance of intermetallic alloys is not yet fully understood. Because the catalytic reaction proceeds on the topmost surface of the particle, it is necessary to clarify the relationship between the periodic structure of the intermetallic alloy and the Pt atomic coordination on the surface.

Development of LAT1-Selective Nuclear Medicine Therapeutics Using Astatine-211.

We investigated nuclear medicine therapeutics targeting the L-type amino acid transporter 1 (LAT1). We previously reported that a nuclear medicine therapeutic drug using astatine 211 (At), an alpha-emitting nuclide that can be produced in an accelerator and targets LAT1 as a molecular target, is effective. The seed compound was 3-[At] Astato-α-methyl-L-tyrosine (At-AAMT-OH-L).

Comparison Length of Linker in Compound for Nuclear Medicine Targeting Fibroblast Activation Protein as Molecular Target.

Novel nuclear medicine therapeutics are being developed by labeling medium-molecular-weight compounds with short-lived alpha-emitting radionuclides. Fibroblast activation protein α (FAPα) is recognized as a highly useful molecular target, and its inhibitor, FAPI, is a compound capable of , both therapeutic and diagnostic, for cancer treatment. In this study, we compared the functions of two compounds that target FAPα: At-FAPI1 and At-FAPI2.

Evaluation of Targeted Alpha Therapy Using [At]FAPI1 in Triple-Negative Breast Cancer Xenograft Models.

Triple-negative breast cancer (TNBC) presents limited therapeutic options and is associated with poor prognosis. Early detection and the development of novel therapeutic agents are therefore imperative. Fibroblast activation protein (FAP) is a membrane protein expressed on cancer-associated fibroblasts (CAFs) that plays an essential role in TNBC proliferation, migration, and invasion.

Dose-efficient phase-contrast imaging of thick weak phase objects via OBF STEM using a pixelated detector.

Optimum bright-field scanning transmission electron microscopy (OBF STEM) is a recently developed low-dose imaging technique that uses a segmented or pixelated detector. While we previously reported that OBF STEM with a segmented detector has a higher efficiency than conventional STEM techniques such as annular bright field (ABF), the imaging efficiency is expected to be further improved by using a pixelated detector. In this study, we adopted a pixelated detector for the OBF technique and investigated the imaging characteristics.

Ferroelectric freestanding hafnia membranes with metastable rhombohedral structure down to 1-nm-thick.

Two-dimensional freestanding membranes of materials, which can be transferred onto and make interfaces with any material, have attracted attention in the search for functional properties that can be utilized for next-generation nanoscale devices. We fabricated stable 1-nm-thick hafnia membranes exhibiting the metastable rhombohedral structure and out-of-plane ferroelectric polarizations as large as 13 μC/cm. We also found that the rhombohedral phase transforms into another metastable orthorhombic phase without the ferroelectricity deteriorating as the thickness increases.

Preclinical Evaluation of Biodistribution and Toxicity of [At]PSMA-5 in Mice and Primates for the Targeted Alpha Therapy against Prostate Cancer.

Astatine (At) is a cyclotron-produced alpha emitter with a physical half-life of 7.2 h. In our previous study, the At-labeled prostate-specific membrane antigen (PSMA) compound ([At]PSMA-5) exhibited excellent tumor growth suppression in a xenograft model.

Production of [At]NaAt solution under GMP compliance for investigator-initiated clinical trial.

Background: The alpha emitter astatine-211 (At) is garnering attention as a novel targeted alpha therapy for patients with refractory thyroid cancer resistant to conventional therapy using beta emitter radioiodine (I). Herein, we aimed to establish a robust method for the manufacturing and quality control of [At]NaAt solution for intravenous administration under the good manufacturing practice guidelines for investigational products to conduct an investigator-initiated clinical trial.

Results: At was separated and purified via dry distillation using irradiated Bi plates containing At obtained by the nuclear reaction of Bi(He, 2n)At.

Neopentyl glycol-based radiohalogen-labeled amino acid derivatives for cancer radiotheranostics.

Background: L-type amino acid transporter 1 (LAT1) is overexpressed in various cancers; therefore, radiohalogen-labeled amino acid derivatives targeting LAT1 have emerged as promising candidates for cancer radiotheranostics. However, At-labeled amino acid derivatives exhibit instability against deastatination in vivo, making it challenging to use At for radiotherapy. In this study, radiohalogen-labeled amino acid derivatives with high dehalogenation stability were developed.

Comparison of Nuclear Medicine Therapeutics Targeting PSMA among Alpha-Emitting Nuclides.

Currently, targeted alpha therapy (TAT) is a new therapy involving the administration of a therapeutic drug that combines a substance of α-emitting nuclides that kill cancer cells and a drug that selectively accumulates in cancer cells. It is known to be effective against cancers that are difficult to treat with existing methods, such as cancer cells that are widely spread throughout the whole body, and there are high expectations for its early clinical implementation. The nuclides for TAT, including Tb, At, Bi, Pb (for Bi), Ra, Ac, Th, and U, are known.

Development and Utility of an Imaging System for Internal Dosimetry of Astatine-211 in Mice.

In targeted radionuclide therapy, determining the absorbed dose of the ligand distributed to the whole body is vital due to its direct influence on therapeutic and adverse effects. However, many targeted alpha therapy drugs present challenges for in vivo quantitative imaging. To address this issue, we developed a planar imaging system equipped with a cadmium telluride semiconductor detector that offers high energy resolution.

Artifactual atomic displacements on surfaces using annular dark-field images with image simulation.

We investigated artifactual atomic displacements on a Pt (111) surface using annular dark-field (ADF) scanning transmission electron microscopy images under ideal conditions with multi-slice image simulation. Pt atomic columns on the surface exhibited artifact displacement. The bright spots shifted slightly toward the interior of the crystal, indicating that ADF imaging underestimates atomic distance measurements on the crystal surface.

A successful plasma exchange in bridging to rituximab for severe neuropsychiatric lupus and lupus nephritis with viral infections and aspiration pneumonia.

Systematic lupus erythematosus (SLE) is a chronic autoimmune disease involving several organs such as the kidneys, skin, vessels, and central nervous system. Neuropsychiatric SLE (NPSLE) is a life-threatening condition that needs treatment with the combination of glucocorticoids and Immunosuppressants (IS). This includes cyclophosphamide and rituximab (RTX) which can lead to several infections.

Immuno-PET and Targeted α-Therapy Using Anti-Glypican-1 Antibody Labeled with Zr or At: A Theranostic Approach for Pancreatic Ductal Adenocarcinoma.

Glypican-1 (GPC1) is overexpressed in several solid cancers and is associated with tumor progression, whereas its expression is low in normal tissues. This study aimed to evaluate the potential of an anti-GPC1 monoclonal antibody (GPC1 mAb) labeled with Zr or At as a theranostic target in pancreatic ductal adenocarcinoma. GPC1 mAb clone 01a033 was labeled with Zr or At with a deferoxamine or decaborane linker, respectively.

Negative correlation between organ heteroplasmy, particularly hepatic heteroplasmy, and age at death revealed by post-mortem studies of m.3243A > G cases.

Mitochondrial DNA m.3243A > G mutation causes mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and its associated multi-organ disorders, including diabetes. To clarify associations between m.

Direct imaging of local atomic structures in zeolite using optimum bright-field scanning transmission electron microscopy.

Zeolites are used in industries as catalysts, ion exchangers, and molecular sieves because of their unique porous atomic structures. However, direct observation of zeolitic local atomic structures via electron microscopy is difficult owing to low electron irradiation resistance. Subsequently, their fundamental structure-property relationships remain unclear.

Exploring a Nuclear-Selective Radioisotope Delivery System for Efficient Targeted Alpha Therapy.

Targeted alpha therapy (TAT) has garnered significant interest as an innovative cancer therapy. Owing to their high energy and short range, achieving selective α-particle accumulation in target tumor cells is crucial for obtaining high potency without adverse effects. To meet this demand, we fabricated an innovative radiolabeled antibody, specifically designed to selectively deliver At (α-particle emitter) to the nuclei of cancer cells.

Evaluation of Astatine-211-Labeled Fibroblast Activation Protein Inhibitor (FAPI): Comparison of Different Linkers with Polyethylene Glycol and Piperazine.

Fibroblast activation proteins (FAP) are overexpressed in the tumor stroma and have received attention as target molecules for radionuclide therapy. The FAP inhibitor (FAPI) is used as a probe to deliver nuclides to cancer tissues. In this study, we designed and synthesized four novel At-FAPI(s) possessing polyethylene glycol (PEG) linkers between the FAP-targeting and At-attaching moieties.

Advantages of FBPA PET in evaluating early response of anti-PD-1 immunotherapy in B16F10 melanoma-bearing mice: Comparison to FDG PET.

Purpose: PET with L-4-borono-2-[F] fluoro-phenylalanine (FBPA) was reported to be useful to differentiate malignant tumors and inflammation. Although immunotherapy with immune checkpoint inhibitors (ICIs) has been applied to cancer treatment recently, FDG PET may not be suitable to determine the effect of ICIs because of false-positive findings caused by treatment-related inflammation. In this study, we aimed to demonstrate that FBPA PET allowed detection of the early response of anti-PD-1 immunotherapy in tumor-bearing mice, comparing the results with those of FDG PET.

Mathematical Model for Evaluation of Tumor Response in Targeted Radionuclide Therapy with At Using Implanted Mouse Tumor.

Recent introduction of alpha-emitting radionuclides in targeted radionuclide therapy has stimulated the development of new radiopharmaceuticals. Preclinical evaluation using an animal experiment with an implanted tumor model is frequently used to examine the efficiency of the treatment method and to predict the treatment response before clinical trials. Here, we propose a mathematical model for evaluation of the tumor response in an implanted tumor model and apply it to the data obtained from the previous experiment of At treatment in a thyroid cancer mouse model.

Effect to Therapy of Sodium-Iodine Symporter Expression by Alpha-Ray Therapeutic Agent via Sodium/Iodine Symporter.

This study confirmed the effect of sodium/iodine symporter (NIS) expression on existing drugs by in vitro and in vivo tests using cultured cell lines. The tumor growth inhibitory effect of sodium astatide ([At]NaAt) was evaluated by in vitro and in vivo tests using human thyroid cancer cells (K1, K1/NIS and K1/NIS-DOX). NIS expression in cancer cells was controlled using the Tet-On system.

Targeted α-therapy using astatine (At)-labeled PSMA1, 5, and 6: a preclinical evaluation as a novel compound.

Purpose: Targeted α-therapy (TAT) for prostate-specific membrane antigen (PSMA) is a promising treatment for metastatic castration-resistant prostate cancer (CRPC). Astatine is an α-emitter (half-life=7.2 h) that can be produced by a 30-MeV cyclotron.