Novel [Ga/Lu]Ga/Lu-AZ-093 as PSMA-Targeting Agent for Diagnosis and Radiotherapy.

Prostate-specific membrane antigen (PSMA) overexpressed in prostate cancer cells can serve as a target for imaging and radioligand therapy (RLT). Previously, [Ga]Ga-P16-093, containing a Ga(III) chelator, ,'-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-,'-diacetic acid (HBED-CC), displayed excellent PSMA-targeting properties and showed a high tumor uptake and retention useful for diagnosis in prostate cancer patients. Recently, [Lu]Lu-PSMA-617 has been approved by the U.

Comparison of novel PSMA-targeting [Lu]Lu-P17-087 with its albumin binding derivative [Lu]Lu-P17-088 in metastatic castration-resistant prostate cancer patients: a first-in-human study.

Purpose: Prostate-specific membrane antigen (PSMA) is a promising target for diagnosis and radioligand therapy (RLT) of prostate cancer. Two novel PSMA-targeting radionuclide therapy agents, [Lu]Lu-P17-087, and its albumin binder modified derivative, [Lu]Lu-P17-088, were evaluated in metastatic castration-resistant prostate cancer (mCRPC) patients. The primary endpoint was dosimetry evaluation, the second endpoint was radiation toxicity assessment (CTCAE 5.

Serotonin transporter imaging agent as a probe for β-cells of pancreas.

Objective: Diabetes mellitus (DM) is one of the major diseases in the world. Nuclear medicine imaging may be able to detect functional status of pancreatic β cells in vivo, which might elucidate the pathological mechanisms of diabetes and develop individualized treatment plans. In this study, we evaluated the ability of [I]ADAM, a serotonin transporter (SERT) imaging agent, as a probe for detecting pancreatic β-cell mass (BCM).

Free Energy Landscape of Type III Fibronectin Domain with Identified Intermediate State and Hierarchical Symmetry.

The tenth domain of type III fibronectin (FNIII_{10}) mediates cell adhesion to the extracellular matrix. Despite its structural similarity to immunoglobulin domains, FNIII_{10} exhibits unique unfolding behaviors. We employed magnetic tweezers to investigate the unfolding and folding dynamics of FNIII_{10} under physiological forces (4-50 pN).

[Ga]Ga-HBED-CC-FAPI Derivatives with Improved Radiolabeling and Specific Tumor Uptake.

Fibroblast activation protein (FAP) is selectively expressed in tumors and highly important for maintaining the microenvironment in malignant tumors. Radioisotope-labeled FAP inhibitors (FAPIs) were proven to be useful for diagnosis and radionuclide therapy of cancer and are under active clinical investigations. Ga-HBED complex displays a higher stability constant (log: 38.

Head-to-Head Comparison of 68 Ga-P16-093 and 68 Ga-PSMA-617 PET/CT in Patients With Primary Prostate Cancer : A Pilot Study.

Purpose: We aimed to compare the diagnostic performance of 68 Ga-P16-093 and 68 Ga-PSMA-617 PET/CT in primary prostate cancer (PCa) patients.

Patients And Methods: Thirty untreated primary PCa patients were enrolled. Each patient underwent 68 Ga-P16-093 and 68 Ga-PSMA-617 PET/CT within a week.

In vivo and in vitro binding of [ I]I-R-(+)-TISCH: A dopamine D receptor ligand for studying pancreatic β-cell mass.

Diabetes mellitus (DM) and insulinoma are mainly affected by the status of pancreatic β-cell mass (BCM). Development of imaging agents for BCM allows to study pancreatic β cells and the relationship between β cells and DM or insulinoma. In this study, we investigated the density of dopamine D receptor on the β cells and measured BCM by statistical image processing.

Free-energy landscape of two-state protein acylphosphatase with large contact order revealed by force-dependent folding and unfolding dynamics.

Acylphosphatase (AcP) is a small protein with 98 amino acid residues that catalyzes the hydrolysis of carboxyl-phosphate bonds. AcP is a typical two-state protein with slow folding rate due to its relatively large contact order in the native structure. The mechanical properties and unfolding behavior of AcP has been studied by atomic force microscope.

Clinical value of serum miR-92 and miR-122 expression level combined with pulmonary ultrasound score in the prognosis of neonatal acute respiratory distress syndrome.

Purpose: To explore the value of the expression of serum miR-92 and miR-122 combined with lung ultrasound score (LUS) in the prognosis of neonatal acute respiratory distress syndrome (ARDS).

Patients And Methods: This study involved 148 neonatal ARDS cases from January 2018 to October 2021, of which 77 children were discharged from hospital and 31 died. The children with ARDS were classified according to disease severity based on X-ray examination as mild (n = 69 cases) and severe (n = 39 cases).

Exploring the Key Factors of Shared Decision-Making Through an Influential Network Relation Map: The Orthopedic Nurse's Perspective.

Background: Few studies have used quantitative methods to explore the key factors affecting shared decision-making (SDM) in nursing decision-making from the perspective of orthopedic nurses.

Purpose: To understand the intercorrelations among shared decision-making questionnaire-nurse (SDM-Q-NUR) factors and identify key factors for clinical nursing care decisions in orthopedics.

Methods: In May 2021, this study investigated the interdependence of the SDM-Q-NUR scale and developed an influential network-relation map (INRM) from the clinical experience of 13 trained orthopedic nurses using the Decision-making Trial and Evaluation Laboratory method.

Kit-based preparation of [Ga]Ga-P16-093 (PSMA-093) using different commercial Ge/Ga generators.

Purpose: Prostate-specific membrane antigen (PSMA) is an important biomarker for molecular imaging and a target for radionuclide therapy of prostate cancer. Recently, U.S.

Evaluating [Ga]Ga-p14-032 as a Novel PET Tracer for Diagnosis Cerebral Amyloid Angiopathy.

We aimed to investigate the distribution of [Ga]Ga-p14-032, a novel PET ligand that binds to vascular amyloid, in patients diagnosed clinically with probable cerebral amyloid angiopathy (CAA) compared with patients with Alzheimer's disease (AD) and normal controls (NC). This longitudinal cohort study was composed of 10 subjects (three probable CAA patients, two AD patients, five NC subjects), recruited from a clinic in China. CAA patients had a history of lobar intracerebral hemorrhage (ICH) and met modified Boston criteria for probable CAA.

Two energy barriers and a transient intermediate state determine the unfolding and folding dynamics of cold shock protein.

Cold shock protein (Csp) is a typical two-state folding model protein which has been widely studied by biochemistry and single molecule techniques. Recently two-state property of Csp was confirmed by atomic force microscopy (AFM) through direct pulling measurement, while several long-lifetime intermediate states were found by force-clamp AFM. We systematically studied force-dependent folding and unfolding dynamics of Csp using magnetic tweezers with intrinsic constant force capability.

Protein folding mechanism revealed by single-molecule force spectroscopy experiments.

Force spectroscopy experiments use mechanical force as a control factor to regulate the folding and unfolding process of proteins. Atomic force microscopy has been widely used to study the mechanical stability of proteins, and obtained unfolding forces and unfolding distance of different proteins, while recently, more low force folding and unfolding measurements were done by optical tweezers and magnetic tweezers. Due to the relatively small distortion of the free energy landscape, low force measurements give the free energy landscape information over bigger conformational space.

Ga-labelled-exendin-4: New GLP1R targeting agents for imaging pancreatic β-cell and insulinoma.

Objective: Glucagon-like peptide-1 receptor (GLP1R) specifically expressed on the surface of pancreatic β-cells and insulinoma, is a potential biomarker for imaging β-cell mass (BCM). In this study, two new Ga-labelled GLP1R targeting agents were prepared and their biological properties for imaging BCM and insulinoma were evaluated.

Methods: [Ga]Ga-HBED-CC-MAL-Cys-exendin-4 ([Ga]Ga-4) and its dimer ([Ga]Ga-5) were synthesized from corresponding precursors.

Head-to-head comparison of [ Ga]Ga-P16-093 and [ Ga]Ga-PSMA-617 in dynamic PET/CT evaluation of the same group of recurrent prostate cancer patients.

Purpose: This study was prospectively designed to evaluate the early dynamic organ distribution and tumor detection capability of [ Ga]Ga-P16-093, which was compared with [ Ga]Ga-PSMA-617 in the same group of recurrent prostate cancer patients.

Methods: Twenty patients with recurrent prostate cancer were enrolled. In 2 consecutive days, each patient underwent a 60-min dynamic PET/CT scan after intravenous administration of 148-185 MBq (4-5 mCi) [ Ga]Ga-P16-093 and [ Ga]Ga-PSMA-617, respectively.

SpyTag/SpyCatcher tether as a fingerprint and force marker in single-molecule force spectroscopy experiments.

Single molecule force spectroscopy has emerged as a powerful tool to study protein folding dynamics, ligand-receptor interactions, and various mechanobiological processes. High force precision does not necessarily lead to high force accuracy, as the uncertainties in calibration can bring serious systematic errors. In the case of magnetic tweezers, accurate determination of the applied forces for short biomolecular tethers, by measuring thermal fluctuations of inhomogeneous magnetic beads, remains difficult.

Development and validation of a kit formulation of [Ga]Ga-P15-041 as a bone imaging agent.

One of the commonly performed studies in nuclear medicine are bone scans with [Tc]Tc-methylene diphosphonate (MDP) for detecting various bone lesions, including cancer metastasis. The recent emergence of commercially available Ge/Ga radionuclide generators makes it possible to provide Ga-labelled bisphosphonates as positron emission tomography (PET) tracers for bone imaging. Preliminary human studies suggested that [Ga]Ga-HBED-CC-BP ([Ga]Ga-P15-041) in conjunction with PET/computed tomography (CT) showed accumulation in known bone lesions, fast clearance from blood and soft tissue, and an ability to provide high contrast images.

Hidden Intermediate State and Second Pathway Determining Folding and Unfolding Dynamics of GB1 Protein at Low Forces.

Atomic force microscopy experiments found that GB1, a typical two-state model protein used for study of folding and unfolding dynamics, can sustain forces of more than 100 pN, but its response to low forces still remains unclear. Using ultrastable magnetic tweezers, we discovered that GB1 has an unexpected nonmonotonic force-dependent unfolding rate at 5-160 pN, from which a free energy landscape with two main barriers and a hidden intermediate state was constructed. A model combining two separate models by Dudko et al.

[Ga]Ga-HBED-CC-DiAsp: A new renal function imaging agent.

Introduction: [Ga]Ga-EDTA ([Ga]Ga-ethylenediaminetetraacetic acid) was previously reported as a renal imaging agent for measuring GFR (glomerular filtration rate). In an effort to provide new agents with better in vivo characteristics for renal imaging, [Ga]Ga-HBED-CC-DiAsp (Di-Aspartic acid derivative of N,N'-bis [2-hydroxy-5-(carboxyethyl)benzyl]-ethylenediamine-N,N'-diacetic acid) was prepared and tested.

Method: HBED-CC-DiAsp was synthesized and labeled with [Ga]GaCl at room temperature.

An improved preparation of [ F]AV-45 by simplified solid-phase extraction purification.

Amyvid (florbetapir f18, [ F]AV-45, [ F]5) was the first FDA-approved positron emission tomography imaging agent targeting β-amyloid (Aβ) plaques for assisting the diagnosis of Alzheimer disease. This work aimed to improve the [ F]AV-45 ([ F]5) preparation by using solid-phase extraction (SPE) purification. [ F]AV-45 ([ F]5) was synthesized by direct nucleophilic radiofluorination of O-tosylated precursor (1 mg) at 120°C in anhydrous dimethyl sulfoxide (DMSO), followed by acid hydrolysis of the N-Boc protecting group.

Rapid screening of nine unradiolabeled candidate compounds as PET brain imaging agents using cassette-wave microdosing and LC-MS/MS.

The R&D of PET imaging agents is a complex system engineering, simplifying screening steps and increasing screening efficiency have become popular issues. The purpose of this study is to develop a new screening procedure using cassette-wave microdosing and LC-MS/MS to enhance the screening throughput of unradiolabeled candidate compounds as PET imaging agents. Nine compounds were divided into 3 sets and made into 3 cassettes.

Synthesis and preliminary evaluation of a novel glutamine derivative: (2S,4S)4-[F]FEBGln.

We report the preparation of a novel glutamine derivative, (2S,4S)-2,5-diamino-4-(4-(2-fluoroethoxy)benzyl)-5-oxopentanoic acid, (2S, 4S)4-[F]FEBGln ([F]4), through efficient organic and radiosyntheses. In vitro assays of [F]4 using MCF-7 cells showed that it entered cells via multiple amino acid transporter systems including system L and ASC2 transporters but not through the system A transporter. [F]4 showed promising properties for tumor imaging and may serve as a lead compound for further optimizing and targeting the system L transporter associated with enhanced glutamine metabolism in cancer cells.