Outcomes of patients aged 70 years or younger with aggressive ATL at core hospitals for ATL treatment in Tokyo.

Adult T-cell leukemia-lymphoma (ATL) is one of the most intractable peripheral T-cell neoplasms caused by human T-cell leukemia virus type I (HTLV-1) infection. Recently, the incidence of HTLV-1 infection and ATL has increased in non-endemic metropolitan areas in Japan. This retrospective study evaluated the clinical features and outcomes of patients with aggressive ATL aged 70 years or younger treated at a core hospital in Tokyo between 2004 and 2016.

Characterization of genetic mutations in hepatitis B virus isolated from HBsAg+/HBcAb+/HBsAb-/HBV DNA + Japanese blood donors.

In Japan, a universal hepatitis B (HB) vaccination was introduced in 2016. Through continuous analysis of HBV DNA mutations, the changes in HBV prevalence before and after the introduction of the universal HB vaccine can be monitored. In this study, we conducted mutational analysis of HBV DNA in HB small protein antigen-positive/HBV core antibody-positive/HB small protein antibody-positive/HBV DNA-positive donor blood samples, with the aim of establishing a baseline prior to the introduction of universal vaccination.

[RI Therapy for Hematopoietic Tumors, Targeted α-Particle Therapy, and Future Prospects for Nuclear Medicine Therapies].

Nuclear medicine treatment is a treatment in which RI is administered to patients, and hematopoietic tumors were treated with 90Y-conjugated anti-CD20 antibodies for low-grade B-cell lymphoma from 2008 to 2021. Targeted α-particle therapy has attracted attention because they have a remarkable therapeutic effect and is effective in cases refractory to β-particle therapy. In Japan, astatine-211(211At)-labeled drugs are being developed due to the restriction of the production and supply of actinium-225(225Ac).

Multivalent At-Radiolabeled Fibroblast Activation Protein Inhibitors for Targeted Alpha-Therapy of Glioma.

Multivalent ligand strategy prevails recently in the design of radioligands for small-molecules due to its successes in enhancing the therapeutic efficacy of radiometallic ligands. In this work, At-FAPI-Dimer and At-APBA-FAPI-Dimer, two multivalent At-conjugated fibroblast activation protein inhibitors (FAPIs), were successfully synthesized with the expectation of narrowing the significant gap between extant radioastatinated FAPIs and clinical application. Cellular pharmacokinetic assessments show that the multivalent strategy could improve the cellular internalization and retention of the radioligand but compromise cellular uptake efficiency relative to monovalent FAPI ligand.

Mutual Tissue Microchimerism of Hepatoblastomas in Monozygotic Twins From a Familial Adenomatous Polyposis Family.

Patients with familial adenomatous polyposis (FAP) have increased risk of hepatoblastoma (HB). We report monozygotic twins with HB in a FAP family. To explore genetic alterations in the HBs of the twins, we carried out whole exome sequencing (WES), RNA-seq, and immunohistochemical analyses of the tumors.

Giant extrachromosomal element "Inocle" potentially expands the adaptive capacity of the human oral microbiome.

Survival strategy of bacteria is expanded by extrachromosomal elements (ECEs). However, their genetic diversity and functional roles for adaptability are largely unknown. Here, we discover a novel family of intracellular ECEs using 56 saliva samples by developing an efficient microbial DNA extraction method coupled with long-read metagenomics assembly.

Production of At and automated radiosynthesis of [At]MABG via electrophilic astatodesilylation.

Background: [At]m-Astatobenzylguanidine ([At]MABG) has demonstrated potent antitumor efficacy in preclinical models of malignant neuroendocrine tumours including neuroblastoma and pheochromocytoma/paraganglioma. The high linear energy transfer and short tissue penetration range of alpha particles enable highly localized cytotoxic effects, potentially overcoming therapeutic limitations associated with conventional beta-emitting radiopharmaceuticals. However, under clinical-scale (i.

Engineering a Radiohybrid PSMA Ligand with an Albumin-Binding Moiety and Pharmacokinetic Modulation via an Albumin-Binding Competitor for Radiotheranostics.

The prostate-specific membrane antigen (PSMA) is a well-established target for radiotheranostics in prostate cancer. We previously demonstrated that 4-(-astatophenyl)butyric acid (APBA), an albumin-binding moiety (ABM) labeled with astatine-211 (At), enables the modulation of pharmacokinetics and enhancement of therapeutic efficacy when combined with the post-administration of an albumin-binding competitor. However, this strategy has not been explored in PSMA-targeting ligands.

Regional assessment is useful for identifying populations at high-risk of hepatitis B virus transmission: A nationwide analysis of population-based surveillance including the COVID-19 pandemic era.

Prevention of new infections is important for the elimination of viral hepatitis B. Assessing the impact of the Coronavirus disease 2019 (COVID-19) pandemic on hepatitis B incidence is important for future infection control measures. A recent hospital-based questionnaire survey implied that a regional assessment in each country would be useful for establishing new preventive measures.

A non-invasive, reference region-based method for quantification of cerebral blood flow and oxygen metabolism using oxygen-15 labeled gases and positron emission tomography.

Objectives: Measurement of cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO) by positron emission tomography (PET) with oxygen-15 labeled gases is widely used for investigation into the pathophysiology of occlusive cerebrovascular disease. However, all methods for quantification of CBF, CBV, OEF, and CMRO by PET with oxygen-15 labeled gases require invasive arterial blood sampling. The present study developed a reference region-based method for quantification of CBF, CBV, OEF, and CMRO using PET and oxygen-15 labeled gases based on the steady-state method without invasive arterial blood sampling.

Macranthoside B Enhances Paclitaxel-induced Human Cervical Cancer Cell Apoptosis Through ROS-JNK Pathway.

Background/aim: This study aims to elucidate whether Macranthoside B (MB) intensifies paclitaxel (PTX)-induced apoptosis in human cervical adenocarcinoma HeLa cells as well as the underlying mechanisms.

Materials And Methods: The MTT assay was used to test the HeLa cell viability after MB and PTX co-treatment, and colony formation assay was utilized to evaluate cell proliferation. Reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were analyzed by flow cytometry.

Extended single-dose toxicity study of [At]meta-astatobenzylguanidine in normal mice in preparation for the first-in-human clinical trial of targeted alpha therapy for pheochromocytoma and paraganglioma.

Objective: Targeted alpha-particle therapy (TAT) is promising with a greater therapeutic effect than conventional beta radionuclide therapy. To develop human clinical trials of [At]meta-astatobenzylguanidine ([At]MABG), we have conducted an extended single-dose toxicity study of [At]MABG in normal mice in consultation with the Pharmaceuticals and Medical Devices Agency (PMDA). We are currently working for human clinical trials of [At]MABG.

Sequential Radiosynthetic Methodology: Assembly of Boronic Ester Precursors on a Diol Resin and Radioiodination Using Copper-Mediated Radioiododeboronation and Azide-Alkyne Cycloaddition.

A streamlined radiosynthetic methodology enables the precise sequential assembly of boronic ester precursors on diol resin, seamlessly integrating copper-mediated radioiododeboronation and azide-alkyne cycloaddition. This approach yields radioiodinated compounds with high radiochemical conversion (>90%) without requiring column purification until the final stage, thereby accelerating the efficient development of advanced radioiodinated molecular probes.

Neurogenin 2-induced central neurons generated from NPC patient-derived iPSC display attenuated neurite outgrowth while accumulating cholesterol.

Niemann-Pick disease type C (NPC) is a lysosome disease hallmarked by autosomal recessive mutations in the NPC1 or NPC2 genes. It results in the accumulation of unesterified cholesterol in the late endosome/lysosome compartment, and then induces progressive neurodegeneration in affected individuals. Previous studies have primarily used fibroblasts derived from NPC patients to examine the cellular pathology and test therapeutic agents.

Prediction of intrahepatic covalently closed circular DNA levels in patients with resolved hepatitis B virus infection: Impact of serum antibody to hepatitis B core antigen titers.

Aim: The correlation between intrahepatic covalently closed circular DNA (cccDNA) levels and serum hepatitis B virus (HBV) markers in patients with resolved HBV infection (hepatitis B surface antigen [HBsAg]-negative and antibody to hepatitis B core antigen [anti-HBc]-positive) is unclear. We therefore examined the utility of anti-HBc titers as a surrogate marker of intrahepatic cccDNA levels in patients with resolved HBV infections.

Methods: Among 1005 patients who underwent hepatectomy between 2010 and 2018, a retrospective review was performed in 114 patients (76 with resolved HBV infection and 38 HBsAg-positive) with frozen specimens of the background liver.

Comparison and cutoff values of two amyloid PET scaling methods: centiloid scale and amyloid-β load.

Objective: To enhance amyloid-β (Aβ) positron emission tomography (PET) diagnostic accuracy and adjust for tracer differences, the amyloid-β load (Aβ) and centiloid (CL) scale were developed. However, the correlation and superiority of these indicators remain unclear. This study aimed to elucidate the correlation and determine cutoff values.

A web questionnaire-based survey on post-COVID-19 condition for infectious disease specialists in Japan.

Introduction: A nationwide survey was conducted to elucidate the current status and challenges of post-COVID-19 condition (PCC) management in Japanese medical institutions with infectious disease specialists, as PCC remains a significant health concern about accumulating knowledge regarding its impact on quality of life.

Materials And Methods: Between January 18 and March 9, 2024, a web-based survey comprising up to 24 questions was administered to 880 infectious disease specialists nationwide. The survey investigated respondents' attributes and backgrounds, management experience, patient characteristics, treatment status, and PCC conditions among medical staff.

Enhancer of zeste homolog 1/2 dual inhibitor valemetostat outperforms enhancer of zeste homolog 2-selective inhibitors in reactivating latent HIV-1 reservoirs .

For the eradication of human immunodeficiency virus type 1 (HIV-1) provirus from people living with HIV-1, reactivation of latently HIV-1-infected cells is essential. Although several latency reversing agents have been identified, eradication of HIV-infected cells has been a challenge. Here, we investigated whether the novel enhancer of zeste homolog 1/2 (EZH1/2) dual inhibitor valemetostat/DS-3201/()-OR-S2 could efficiently reactivate latently HIV-1-infected cells and .

Left ventricular diastolic inflow and myocardial flow reserve in patients with coronary artery disease: simultaneous analysis of 4D-Flow and myocardial perfusion using hybrid PETMR.

Purpose: This study aimed to simultaneously evaluate the association between diastolic left ventricular (LV) inflow and myocardial flow reserve (MFR) using a hybrid PET/MR system in patients with coronary artery disease (CAD).

Methods: Sixty-seven patients (mean 66 ± 15 years, male 55) with CAD who underwent rest-pharmacological stress N-ammonia PET/MR were included. MFR, perfusion defect, and peak filling rate (PFR) were obtained through rest-stress PET.

[New Investment for Theranostics in Europe].

The Japanese government has shown increasing expectations for the medical application of radioactive isotopes (RIs), as reflected in the 2024 Basic Policy on Economic and Fiscal Management and Reform. Additionally, the Fukushima Instutute for Research, Education and Innovation (F-REI) has launched RI-based diagnostic and therapeutic drug development projects, and the Ministry of Health, Labour and Welfare has proposed a draft guideline for clinical and non-clinical studies of radiopharmaceuticals for therapeutic use. Meanwhile, in Europe, three large-scale theranostics projects began in October 2024.

Analysis of clinical factors associated with incomplete standard protocol Lu-DOTATATE treatment in neuroendocrine tumor patients.

Purpose: To investigate the clinical features of patients with neuroendocrine tumors (NETs) who could not complete the standard protocol (4 cycles of 7.4 GBq per 8 weeks) Lu-DOTATATE treatment.

Materials And Methods: A retrospective single-center analysis was conducted on 26 patients who underwent Lu-DOTATATE treatment between December 2021 and August 2024.

Design of a Tetravalent RGD Peptide Capable of Simultaneous Binding with Multiple Integrin αvβ3 for Targeted Radionuclide Therapy.

For targeted radionuclide therapy, radioligands that exhibit high and persistent tumor uptake are indispensable. We previously synthesized a Tc-labeled hexavalent RGD peptide (Tc-(RGD)) as a tumor imaging agent targeting integrin αvβ3. Tc-(RGD) showed high in vivo tumor uptake with long retention due to simultaneous binding to multiple integrin αvβ3 receptors.