A Phase II Study of I-rituximab for Patients With Relapsed or Refractory Marginal Zone Lymphoma.

Background: Radioimmunotherapy (RIT) is a rare treatment option for relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL). We investigated the safety and efficacy of I-rituximab in patients with relapsed or refractory marginal zone lymphomas.

Methods: Patients with pathologically confirmed marginal zone lymphoma who relapsed or were resistant to prior therapy were enrolled.

Comparison of the Effects of DOTA and NOTA Chelators on Cu-Cudotadipep and Cu-Cunotadipep for Prostate Cancer.

Background: This study compared the effects of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) as Cu-chelating agents in newly developed prostate-specific membrane antigen (PSMA) target compounds, Cu-cudotadipep and Cu-cunotadipep, on pharmacokinetics.

Methods: The in vitro stability of the chelators was evaluated using human and mouse serum. In vitro PSMA-binding affinity and cell uptake were compared using human 22Rv1 cells.

Exploration of Tetrahydroisoquinoline- and Benzo[]azepine-Based Sphingosine 1-Phosphate Receptor 1 Agonists for the Treatment of Multiple Sclerosis.

Because of the wide use of Fingolimod for the treatment of multiple sclerosis (MS) and its cardiovascular side effects such as bradycardia, second-generation sphingosine 1-phosphate receptor 1 (S1P1) agonist drugs for MS have been developed and approved by FDA. The issue of bradycardia is still present with the new drugs, however, which necessitates further exploration of S1P1 agonists with improved safety profiles for next-generation MS drugs. Herein, we report a tetrahydroisoquinoline or a benzo[]azepine core-based S1P1 agonists such as and after systematic examination of hydrophilic groups and cores.

Radioimmunotherapy with I-rituximab for patients with relapsed or refractory follicular or mantle cell lymphoma.

Aim: This study aimed to evaluate the safety and efficacy of I-rituximab in patients with relapsed or refractory follicular or mantle cell lymphoma.

Methods: Twenty-four patients with relapsed or refractory follicular or mantle cell lymphoma were administered unlabeled rituximab (70 mg) immediately before receiving a therapeutic dose of I-rituximab. Contrast-enhanced 18F-fluorodeoxyglucose positron emission tomography/computed tomography was used a month later to assess tumor response.

The role of 18F-FDG PET/CT in patients with diffuse large B-cell lymphoma after radioimmunotherapy using 131I-rituximab as consolidation therapy.

Purpose: To evaluate the prognostic value of pretreatment 18F-FDG PET/CT after consolidation therapy of 131I-rituximab in patients with diffuse large B-cell lymphoma (DLBCL) who had acquired complete remission after receiving chemotherapy.

Methods: Patients who were diagnosed with DLBCL via histologic confirmation were retrospectively reviewed. All patients had achieved complete remission after 6 to 8 cycles of R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisolone) chemotherapy after which they underwent consolidation treatment with 131I-rituximab.

64 Cu-DOTA-Rituximab PET/CT of B-Cell Non-Hodgkin Lymphoma for Imaging the CD20 Expression.

64 Cu-DOTA-rituximab PET/CT was performed on a 62-year-old and a 71-year-old men diagnosed with B-cell non-Hodgkin lymphoma. Compared with 18 F-FDG PET/CT, lesions could be detected more sensitively, and it was confirmed that there was no discernible 64 Cu-DOTA-rituximab uptake in the tumor other than lymphoma. 64 Cu-DOTA-rituximab PET/CT could be a powerful tool for the diagnosis and monitoring treatment response of lymphoma because of imaging the CD20 expression.

The Prediction of HER2-Targeted Treatment Response Using Cu-Tetra-Azacyclododecanetetra-Acetic Acid (DOTA)-Trastuzumab PET/CT in Metastatic Breast Cancer: A Case Report.

A 45-year-old woman diagnosed with breast cancer reported disease progression in the form of metastatic lung and recurrent breast lesions following chemotherapy and human epidermal growth factor receptor 2 (HER2)-targeted therapy. The patient underwent Cu-tetra-azacyclododecanetetra-acetic acid (DOTA)-trastuzumab positron emission tomography/computed tomography (PET/CT) to evaluate the HER2 expression status. Cu-DOTA-trastuzumab accumulated in the left breast and lymph nodes but not in the lung lesions.

Prediction of Neoadjuvant Chemotherapy Response in Osteosarcoma Using Convolutional Neural Network of Tumor Center F-FDG PET Images.

We compared the accuracy of prediction of the response to neoadjuvant chemotherapy (NAC) in osteosarcoma patients between machine learning approaches of whole tumor utilizing fluorine-fluorodeoxyglucose (F-FDG) uptake heterogeneity features and a convolutional neural network of the intratumor image region. In 105 patients with osteosarcoma, F-FDG positron emission tomography/computed tomography (PET/CT) images were acquired before (baseline PET0) and after NAC (PET1). Patients were divided into responders and non-responders about neoadjuvant chemotherapy.

Improving Theranostic Gallium-68/Lutetium-177-Labeled PSMA Inhibitors with an Albumin Binder for Prostate Cancer.

We developed a novel therapeutic radioligand, [Lu], with an albumin binding motif and evaluated it in a prostate-specific membrane antigen (PSMA)-expressing tumor xenograft mouse model. Fourteen PSMA target candidates were synthesized, and binding affinity was evaluated with an competitive binding assay. First, four compound candidates were selected depending on binding affinity results.

CHIP-mediated hyperubiquitylation of tau promotes its self-assembly into the insoluble tau filaments.

The tau protein is a highly soluble and natively unfolded protein. Under pathological conditions, tau undergoes multiple post-translational modifications (PTMs) and conformational changes to form insoluble filaments, which are the proteinaceous signatures of tauopathies. To dissect the crosstalk among tau PTMs during the aggregation process, we phosphorylated and ubiquitylated recombinant tau using GSK3β and CHIP, respectively.

Pharmacophore-Based Virtual Screening of Novel Competitive Inhibitors of the Neurodegenerative Disease Target Kynurenine-3-Monooxygenase.

The pathogenesis of several neurodegenerative diseases such as Alzheimer's or Huntington's disease has been associated with metabolic dysfunctions caused by imbalances in the brain and cerebral spinal fluid levels of neuroactive metabolites. Kynurenine monooxygenase (KMO) is considered an ideal therapeutic target for the regulation of neuroactive tryptophan metabolites. Despite significant efforts, the known KMO inhibitors lack blood-brain barrier (BBB) permeability and upon the mimicking of the substrate binding mode, are subject to produce reactive oxygen species as a side reaction.

A Phase 0 Microdosing PET/CT Study Using O-[18F]Fluoromethyl-d-Tyrosine in Normal Human Brain and Brain Tumor.

Purpose: The aim of the present study was to obtain information about distribution, radiation dosimetry, toxicity, and pharmacokinetics of O-[18F]fluoromethyl-d-tyrosine (d-18F-FMT), an amino acid PET tracer, in patients with brain tumors.

Patients And Methods: A total of 6 healthy controls (age = 19-25 years, 3 males and 3 females) with brain PET images and radiation dosimetry and 12 patients (median age = 60 years, 6 males and 6 females) with primary (n = 5) or metastatic brain tumor (n = 7) were enrolled. We acquired 60-minute dynamic brain PET images after injecting 370 MBq of d-18F-FMT.

Targeted alpha immunotherapy of CD20-positive B-cell lymphoma model: dosimetry estimate of Ac-DOTA-rituximab using Cu-DOTA-rituximab.

Objective: The aim of this study was to evaluate the radiation dosimetry of alpha-emitter Ac-DOTA-rituximab using Monte Carlo simulation of Cu-DOTA-rituximab.

Methods: CD20 expression was evaluated in lymphoma cell lines (Jurkat and Raji). DOTA-rituximab was conjugated and then chelated by Cu.

The translocator protein ligands as mitochondrial functional modulators for the potential anti-Alzheimer agents.

Small molecule modulators of mitochondrial function have been attracted much attention in recent years due to their potential therapeutic applications for neurodegenerative diseases. The mitochondrial translocator protein (TSPO) is a promising target for such compounds, given its involvement in the formation of the mitochondrial permeability transition pore in response to mitochondrial stress. In this study, we performed a ligand-based pharmacophore design and virtual screening, and identified a potent hit compound, () as a TSPO ligand.

A preliminary clinical trial to evaluate Cu-NOTA-Trastuzumab as a positron emission tomography imaging agent in patients with breast cancer.

Background: The purpose of this study was to evaluate both the biodistribution and safety of Cu-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA)-Trastuzumab, a novel Cu-labeled positron emission tomography (PET) tracer for human epidermal growth factor receptor 2 (HER2) in patients with breast cancer.

Methods: PET images at 1, 24, and 48 h after 296 MBq of Cu-NOTA-Trastuzumab injection were obtained from seven patients with breast cancer. Both the primary tumors' and metastatic lesions' maximum standardized uptake value (SUV) was evaluated.

The Feasibility of Cu-PSMA I&T PET for Prostate Cancer.

The goal of this research was to investigate the feasibility of Cu labeling in prostate-specific membrane antigen imaging and therapy (PSMA I&T) for PSMA positron emission tomography (PET) imaging and biodistribution evaluation. PSMA I&T was labeled with Cu, and stability in human and mouse sera was evaluated. Prostate cancer cell lines were used for specific uptake assays (22RV1 for PSMA-positive, PC-3 for -negative).

Early prediction of neoadjuvant chemotherapy response for advanced breast cancer using PET/MRI image deep learning.

This study aimed to investigate the predictive efficacy of positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) for the pathological response of advanced breast cancer to neoadjuvant chemotherapy (NAC). The breast PET/MRI image deep learning model was introduced and compared with the conventional methods. PET/CT and MRI parameters were evaluated before and after the first NAC cycle in patients with advanced breast cancer [n = 56; all women; median age, 49 (range 26-66) years].

Performance of an impedance-variable pulsed high-power electron-beam accelerator based on energy efficient transmission.

Versatile high-power pulsed electron-beam accelerators that meet the requirements of pulsed high-power specifications are needed for appropriate applications in medical industry, defense, and other industries. The pulsed electron beam accelerator comprising a Marx generator and Blumlein pulse forming line (PFL) is designed to accelerate the electron beams at the level of 1 MeV when electrostatically discharging. The performance specifications of Marx generators consisting of a 100 kV DC power supply, R-L-C circuit, and high voltage switch are at a maximum 800 kV.

F-labeled 1,2,3-triazole-linked Glu-urea-Lys-based PSMA ligands have good pharmacokinetic properties for positron emission tomography imaging of prostate cancer.

Background: Prostate-specific membrane antigen (PSMA) is increasingly recognized as an excellent target for prostate cancer imaging and therapy. Finding compounds with a high target-to-nontarget ratio are an important challenge in the development of positron emission tomography (PET) imaging agents. In this study, we attempted to find a suitable compound from a simply-synthesized compound library.

Aggresomal sequestration and STUB1-mediated ubiquitylation during mammalian proteaphagy of inhibited proteasomes.

The 26S proteasome, a self-compartmentalized protease complex, plays a crucial role in protein quality control. Multiple levels of regulatory systems modulate proteasomal activity for substrate hydrolysis. However, the destruction mechanism of mammalian proteasomes is poorly understood.

A microdose clinical trial to evaluate [F]Florastamin as a positron emission tomography imaging agent in patients with prostate cancer.

Purpose: To evaluate the biodistribution of [F]Florastamin, a novel F-labelled positron emission tomography (PET) tracer for prostate-specific membrane antigen (PSMA) for the diagnosis of prostate cancer.

Methods: PET was performed for five healthy controls and 10 patients with prostate cancer at 0, 10, 30, 70, and 120 mins after injecting 370 MBq of [F]Florastamin. The maximum standardised uptake value (SUV) was evaluated in the primary tumour.

The correlation of neuropsychological evaluation with 11C-PiB and 18F-FC119S amyloid PET in mild cognitive impairment and Alzheimer disease.

For the diagnosis of mild cognitive impairment (MCI) and Alzheimer disease (AD), variable neuroimaging and neuropsychological tests have been used. We aimed to evaluate the correlation of neuropsychological domain with new amyloid positron emission tomography (PET) study and to validate the availability of new PET tracer.We enrolled 20 patients who underwent C-PiB-PET/CT, new PET tracer F-FC119S PET/CT from November, 2014 to July, 2015.