In vivo SPECT imaging of Tc-99m radiolabeled exosomes from human umbilical-cord derived mesenchymal stem cells in small animals.

Extracellular vesicles derived from human umbilical cord-derived mesenchymal stem cells (UCMSC-EVs) have been postulated to have therapeutic potential for various diseases. However, the biodistribution and pharmacokinetics of these vesicles are still unclear. For a better understanding of the in vivo properties of UCMSC-EVs, in the present study, these vesicles were first radiolabeled with Technetium-99m (Tc-UCMSC-EVs) and evaluated using in vivo single photon emission computed tomography (SPECT) imaging and biodistribution experiments.

Fluorine-18 labeling PEGylated 6-boronotryptophan for PET scanning of mice for assessing the pharmacokinetics for boron neutron capture therapy of brain tumors.

Two tryptophan compound classes 5- and 6-borono PEGylated boronotryptophan derivatives have been prepared for assessing their aqueous solubility as formulation of injections for boron neutron capture therapy (BNCT). The PEGylation has improved their aqueous solubility thereby increasing their test concentration in 1 mM without suffering from toxicity. In-vitro uptake assay of PEGylated 5- and 6-boronotryptophan showed that the B-10 concentration can reach 15-50 ppm in U87 cell whereas the uptake in LN229 cell varies.

Dextromethorphan moderates reward deficiency associated with central serotonin transporter availability in 3,4-methylenedioxy-methamphetamine-treated animals.

Background: The neurotoxicity of 3,4-methylenedioxy-methamphetamine (MDMA) to the serotonergic system is well-documented. Dextromethorphan (DM), an antitussive drug, decreased morphine- or methamphetamine (MA)-induced reward in rats and may prevent MDMA-induced serotonergic deficiency in primates, as indicated by increased serotonin transporter (SERT) availability. We aimed to investigate the effects of DM on reward, behavioral sensitization, and neurotoxicity associated with loss of SERT induced by chronic MDMA administration in rats.

Evaluation of Chelator-to-Antibody Ratio on Development of Zr-iPET Tracer for Imaging of PD-L1 Expression on Tumor.

Zr-iPET has been widely used for preclinical and clinical immunotherapy studies to predict patient stratification or evaluate therapeutic efficacy. In this study, we prepared and evaluated Zr-DFO-anti-PD-L1-mAb tracers with varying chelator-to-antibody ratios (CARs), including Zr-DFO-anti-PD-L1-mAb_3X (), Zr-DFO-anti-PD-L1-mAb_10X (), and Zr-DFO-anti-PD-L1-mAb_20X (). The DFO-anti-PD-L1-mAb conjugates with varying CARs were prepared using a random conjugation method and then subjected to quality control.

Cyanopyridoimidazole/1,2-Aminothiol Click Reaction: A Novel Bioorthogonal Reaction for Synthesis of Radiotracers.

We herein described the design and synthesis of the cyanopyridoimidazoles (CPIs) as new bioorthogonal click reagents toward 1,2-aminothiol groups. Kinetic and density functional theory-based studies of the synthetic compounds revealed that incorporating an electron-withdrawing substituent into the CPI scaffold lowers its lowest unoccupied molecular orbital energy, consequently increasing reactivity. Optimized CPI showed rapid reactivity and high stability in physiological conditions and has been demonstrated to be suitable for various radiotracer synthetic methods.

Identification of the Hepatic Metabolites of Flumazenil and their Kinetic Application in Neuroimaging.

Studies of the neurobiological causes of anxiety disorders have suggested that the γ-aminobutyric acid (GABA) system increases synaptic concentrations and enhances the affinity of GABA (type A) receptors for benzodiazepine ligands. Flumazenil antagonizes the benzodiazepine-binding site of the GABA/benzodiazepine receptor (BZR) complex in the central nervous system (CNS). The investigation of flumazenil metabolites using liquid chromatography (LC)-tandem mass spectrometry will provide a complete understanding of the in vivo metabolism of flumazenil and accelerate radiopharmaceutical inspection and registration.

Automated Synthesis of [F]Flumazenil Application in GABA Receptor Neuroimaging Availability for Rat Model of Anxiety.

Clinical studies have demonstrated that the γ-aminobutyric acid type A (GABA) receptor complex plays a central role in the modulation of anxiety. Conditioned fear and anxiety-like behaviors have many similarities at the neuroanatomical and pharmacological levels. The radioactive GABA/BZR receptor antagonist, fluorine-18-labeled flumazenil, [F]flumazenil, behaves as a potential PET imaging agent for the evaluation of cortical damage of the brain in stroke, alcoholism, and for Alzheimer disease investigation.

Antiinflammation Derived Suzuki-Coupled Fenbufens as COX-2 Inhibitors: Minilibrary Construction and Bioassay.

A small fenbufen library comprising 18 compounds was prepared via Suzuki Miyara coupling. The five-step preparations deliver 9-17% biphenyl compounds in total yield. These fenbufen analogs exert insignificant activity against the IL-1 release as well as inhibiting cyclooxygenase 2 considerably.

Synthesis, Radiolabeling, and Preliminary in vivo Evaluation of [Ga] IPCAT-NOTA as an Imaging Agent for Dopamine Transporter.

Introduction: Novel radiotracer development for imaging dopamine transporters is a subject of interest because although [Tc]TRODAT-1, [I]β-CIT, and [I]FP-CIT are commercially available; Mo/Tc generator is in short supply and I production is highly dependent on compact cyclotron. Therefore, we designed a novel positron emission tomography (PET) tracer based on a tropane derivative through C-2 modification to conjugate NOTA for chelating Ga, a radioisotope derived from a Ge/Ga generator.

Methods: IPCAT-NOTA was synthesized and labeled with [Ga]GaCl at room temperature.

Synthesis and evaluation of -[F] fluorocelecoxib for COX-2 cholangiocarcinoma imaging.

Background: An F-tagged NSAID analog was prepared for use as a probe for COX-2 expression, which is associated with tumor development.

Methods: The in vivo uptake of celecoxib was monitored with -[F]fluorocelecoxib using positron emission tomography (PET). The binding affinity of -[F]fluorocelecoxib to COX-1 and COX-2 enzymes were assessed using the competitor celecoxib.

Development and validation of a reversed-phase HPLC method for analysis of radiochemical purity in [I]IBZM.

[I]IBZM is used widely for in vivo imaging of D receptors in human brain and shows relatively fast kinetics and a greater susceptibility to synaptic dopamine release than other single-photon emission computed tomography (SPECT) radioligands. A reliable and reversed-phase HPLC method using UV/VIS and radiometric detectors has been developed for qualitative analysis of BZM and IBZM and radiochemical purity in [I]IBZM preparations. The method uses gradient elution on a Zorbax XDB C-18 column with a mobile phase that consists of 10mM 3,3-dimethylglutaric acid (DMGA), pH 7.

Study of [18F]FLT and [123I]IaraU for cellular imaging in HSV1 tk-transfected murine fibrosarcoma cells: evaluation of the tracer uptake using 5-fluoro, 5-iodo and 5-iodovinyl arabinosyl uridines as competitive probes.

As one of the most intensively studied probes for imaging of the cellular proliferation, [(18)F]FLT was investigated whether the targeting specificity of thymidine kinase 1 (TK1) dependency could be enhanced through a synergistic effect mediated by herpes simplex type 1 virus (HSV1) tk gene in terms of the TK1 or TK2 expression. 5-[(123)I]Iodo arabinosyl uridine ([(123)I]IaraU) was prepared in a radiochemical yield of 8% and specific activity of 21 GBq/μmol, respectively. Inhibition of the cellular uptake of these two tracers was compared by using the arabinosyl uridine analogs such as 5-iodo, 5-fluoro and 5-(E)-iodovinyl arabinosyl uridine along with 2'-fluoro-5-iodo arabinosyl uridine (FIAU).

Development and validation of an anion-exchange HPLC method for the determination of fluoride content and radiochemical purity in [18F]NaF.

(18)F-labeled sodium fluoride ([(18)F]NaF) is a useful bone imaging agent that has been demonstrated to be significantly more accurate than (99m)Tc-labeled methylene diphosphonate for the detection of both sclerotic and lytic lesions in various malignancies. A reliable anion-exchange HPLC method equipped with suppressed conductivity and radioactive detectors has been developed in order to analyze the content of NaF and radiochemical purity in [(18)F]NaF radiopharmaceuticals. The method described for fluoride analysis uses an isocratic elution of NaF in a Hamilton anion-exchange column using a mobile phase that consists of 7.

Development and validation of 2-deoxy-2-chloro-d-glucose impurity analysis in [(18)F]FDG by three potential-time waveforms of high-performance liquid chromatography/pulsed amperometric detection.

A suitable three potential-time waveforms for the electrochemical detection of 2-deoxy-2-chloro-d-glucose (ClDG) by gold working electrode and palladium reference electrode have been developed and method validation was performed on Waters 2796 Bioalliance HPLC system coupled with pulsed amperometric detection (HPLC/PAD). FDG and ClDG could be completely separated by 50 mM NaOH mobile phase at a flow rate of 1.0 ml/min; 30 degrees C analytical column temperature; and E1 of 200 mV, T1 of 900 mS; E2 of -770 mV, T2 of 10 mS; E3 of 1400 mV, T3 of 10 mS; acquisition delay (AD) of 300 mS.