Targeted Thrombolysis with Magnetic Nanotherapeutics: A Translational Assessment.

Plasminogen activators, such as recombinant tissue-type plasminogen activators (rtPAs), while effective in treating thromboembolic diseases, often induce hemorrhagic complications due to non-specific enzyme activities in the systemic circulation. This study evaluated the targeting efficiency, efficacy, biodistribution, and potential toxicity of a rtPA covalently attached to chitosan-coated magnetic nanoparticles (chitosan-MNP-rtPA). The thrombolytic activity of a chitosan-MNP-rtPA was preserved by protection from an endogenous plasminogen activator inhibitor-1 (PAI-1) in whole blood and after circulation in vivo, as examined by thromboelastometry.

Correlation between visual association memory test and structural changes in patients with Alzheimer's disease and amnestic mild cognitive impairment.

Background: Visual association memory test (VAMT) is a brief 6-point cognition test that has been shown to be effective in differentiating Alzheimer's disease (AD) from other types of dementia. This study aimed to investigate the correlation of the VAMT performance with amyloid plaque burden and hippocampal atrophy.

Methods: Fourteen patients with AD, 29 with amnestic mild cognitive impairment (aMCI), and 11 normal cognition (NC) subjects were recruited.

Therapeutic effects of honokiol on motor impairment in hemiparkinsonian mice are associated with reversing neurodegeneration and targeting PPARγ regulation.

Parkinson's disease (PD) is a profound neurodegenerative disorder with gradual loss of dopamine nigrostriatal neurons linked to serious behavioral symptoms. While the current treatment strategies present limitations on halting the progression of PD, this study aimed to investigate the therapeutic potential of honokiol, as a partial peroxisome proliferator-activated receptor-gamma (PPARγ) mimic, on the proceeding behavioral and biochemical alterations in hemiparkinsonian mice. Results showed that unilateral striatal 6-hydroxydopamine (6-OHDA)-lesioned mice exhibited motor impairment, reflecting the contralateral rotation induced by apomorphine at 1-3 weeks post-lesion.

Visualization of ischemic stroke-related changes on F-THK-5351 positron emission tomography.

Background: The F-THK-5351 radiotracer has been used to detect the in vivo tau protein distribution in patients with tauopathy, such as Alzheimer's disease and corticobasal syndrome. In addition, F-THK-5351 can also monitor neuroinflammatory process due to high affinity to astrogliosis. We aimed to explore F-THK-5351 distribution patterns and characteristics in patients with recent ischemic stroke.

Passivating Injured Endothelium with Kinexins in Thrombolytic Therapy.

Without conjunctive administration of an anticoagulant, endothelial injury-induced thrombosis is resistant to thrombolysis and prone to re-thrombosis. We hypothesized that co-delivery of recombinant tissue plasminogen activator (rtPA) with annexin V-containing anticoagulants that specifically target the injured endothelium may passivate the thrombogenic elements of the vascular injury site and enhance rtPA-induced thrombolysis. In this study, the effects of conjunctive administration of Kinexins (Kunitz inhibitor-annexin V fusion proteins) with rtPA on thrombolysis were determined and .

Radiosensitization of ultrasmall GNP-PEG-cRGDfK in ALTS1C1 exposed to therapeutic protons and kilovoltage and megavoltage photons.

Purpose: One of the promising radiosensitizers is the ultrasmall gold nanoparticle (GNP) with a hydrodynamic diameter <3 nm. We studied functionalized ultrasmall GNPs (1.8 nm diameter) coated by polyethylene glycol (PEG) and conjugated with cyclic RGDfK (2.

Early-phase 18F-AV-45 PET Imaging can Detect Crossed Cerebellar Diaschisis Following Carotid Artery Stenosis and Cerebral Hypoperfusion.

Background: Carotid artery stenosis (CAS) may induce cerebral hypoperfusion. Early-phase 18F-Florbetapir (AV-45/Amyvid, 18F-AV-45) positron emission tomography (PET) imaging can provide perfusion-like property (pAV-45) for the estimation of cerebral blood flow (CBF). Supra-tentorial lesions may cause decreased blood flow and metabolism in the contralateral cerebellum known as crossed cerebellar diaschisis (CCD).

[F]FP-(+)-DTBZ PET study in a lactacystin-treated rat model of Parkinson disease.

Objective: Lactacystin has been used to establish rodent models of Parkinson disease (PD), with cerebral α-synuclein inclusions. This study evaluated the uptake of [F]9-fluoropropyl-(+)-dihydrotetrabenazine ([F]FP-(+)-DTBZ), a vesicular monoamine transporter type 2 (VMAT2)-targeting radiotracer, through positron emission tomography (PET) in lactacystin-treated rat brains.

Methods: Adult male Sprague-Dawley rats were randomly treated with a single intracranial dose of lactacystin (2 or 5 μg) or saline (served as the sham control) into the left medial forebrain bundle.

Biodistribution and Radiation Dosimetry for the Tau Tracer F-THK-5351 in Healthy Human Subjects.

F-THK-5351 is a novel radiotracer that demonstrates high binding selectivity and affinity for tau pathology and exhibits better pharmacokinetics in the living brain than previous THK tau probes. The aim of the present study was to estimate the radiation dose of F-THK-5351 in humans and to compare the clinical radiation dosimetry results to estimations published previously with preclinical data. Serial whole-body PET/CT imaging was performed for 240 min on 12 healthy volunteers after injecting F-THK-5351 (mean administered activity, 377.

Quantitative analysis of the therapeutic effect of magnolol on MPTP-induced mouse model of Parkinson's disease using in vivo 18F-9-fluoropropyl-(+)-dihydrotetrabenazine PET imaging.

18F-9-Fluoropropyl-(+)-dihydrotetrabenazine [18F-FP-(+)-DTBZ] positron emission tomography (PET) has been shown to detect dopaminergic neuron loss associated with Parkinson's disease (PD) in human and neurotoxin-induced animal models. A polyphenol compound, magnolol, was recently proposed as having a potentially restorative effect in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)- or 6-hydroxydopamine-treated animal models. In this study, 18F-FP-(+)-DTBZ PET was used to determine the therapeutic efficacy of magnolol in an MPTP-PD mouse model that was prepared by giving an intraperitoneally (i.

Imaging characteristic of dual-phase (18)F-florbetapir (AV-45/Amyvid) PET for the concomitant detection of perfusion deficits and beta-amyloid deposition in Alzheimer's disease and mild cognitive impairment.

Purpose: We investigated dual-phase (18)F-florbetapir (AV-45/Amyvid) PET imaging for the concomitant detection of brain perfusion deficits and beta-amyloid deposition in patients with Alzheimer's disease (AD) and amnestic mild cognitive impairment (MCI), and in cognitively healthy controls (HCs).

Methods: A total of 82 subjects (24 AD patients, 44 MCI patients and 14 HCs) underwent both dual-phase (18)F-AV-45 PET and MRI imaging. Dual-phase dynamic PET imaging consisted of (1) five 1-min scans obtained 1 - 6 min after tracer injection (perfusion (18)F-AV-45 imaging, pAV-45), and (2) ten 1-min scans obtained 50 - 60 min after tracer injection (amyloid (18)F-AV-45 imaging).

Self-assembling bubble carriers for oral protein delivery.

Successful oral delivery of therapeutic proteins such as insulin can greatly improve the quality of life of patients. This study develops a bubble carrier system by loading diethylene triamine pentaacetic acid (DTPA) dianhydride, a foaming agent (sodium bicarbonate; SBC), a surfactant (sodium dodecyl sulfate; SDS), and a protein drug (insulin) in an enteric-coated gelatin capsule. Following oral administration to diabetic rats, the intestinal fluid that has passed through the gelatin capsule saturates the mixture; concomitantly, DTPA dianhydride produces an acidic environment, while SBC decomposes to form CO2 bubbles at acidic pH.

Correlation of Parkinson disease severity and 18F-DTBZ positron emission tomography.

Importance: Currently, diagnosis of Parkinson disease is mainly based on clinical criteria characterized by motor symptoms including bradykinesia, rigidity, resting tremor, and postural instability. Reliable in vivo biomarkers to monitor disease severity and reflect the underlying dopaminergic degeneration are important for future disease-modifying therapy in Parkinson disease.

Objectives: To use [18F]9-fluoropropyl-(+)-dihydrotetrabenazine (18F-DTBZ; [18F]AV-133) positron emission tomography (PET) to explore the characteristics of vesicular monoamine transporter type 2 imaging in patients with Parkinson disease (PD) with different severity levels as well as to investigate its capability in monitoring clinical severity.

Hyperthermia-mediated local drug delivery by a bubble-generating liposomal system for tumor-specific chemotherapy.

As is widely suspected, lysolipid dissociation from liposomes contributes to the intravenous instability of ThermoDox (lysolipid liposomes), thereby impeding its antitumor efficacy. This work evaluates the feasibility of a thermoresponsive bubble-generating liposomal system without lysolipids for tumor-specific chemotherapy. The key component in this liposomal formulation is its encapsulated ammonium bicarbonate (ABC), which is used to actively load doxorubicin (DOX) into liposomes and trigger a drug release when heated locally.

Anoxic androgen degradation by the denitrifying bacterium Sterolibacterium denitrificans via the 2,3-seco pathway.

The biodegradation of steroids is a crucial biochemical process mediated exclusively by bacteria. So far, information concerning the anoxic catabolic pathways of androgens is largely unknown, which has prevented many environmental investigations. In this work, we show that Sterolibacterium denitrificans DSMZ 13999 can anaerobically mineralize testosterone and some C19 androgens.

Comparison of 99mTc-TRODAT-1 SPECT and 18 F-AV-133 PET imaging in healthy controls and Parkinson's disease patients.

Unlabelled: (99m)Tc-TRODAT-1 is the first clinical routine (99m)Tc radiopharmaceutical to evaluate dopamine neurons loss in Parkinson's disease (PD). (18)F-AV-133 is a novel PET radiotracer targeting the vesicular monoamine transporter type 2 (VMAT2) to detect monoaminergic terminal reduction in PD patients. The aim of this study is to compare both images in the same health control (HC) and PD subjects.

Treatment of chemotherapy-induced neutropenia in a rat model by using multiple daily doses of oral administration of G-CSF-containing nanoparticles.

Chemotherapy-induced neutropenia often increases the likelihood of life-threatening infections. In this study, a nanoparticle (NP) system composed of chitosan and poly(γ-glutamic acid) conjugated with diethylene triamine pentaacetic acid (γPGA-DTPA) was prepared for oral delivery of granulocyte colony-stimulating factor (G-CSF), a hematopoietic growth factor. The therapeutic potential of this NP system for daily administration of G-CSF to treat neutropenia associated with chemotherapy was evaluated in a rat model.

In vivo detection of monoaminergic degeneration in early Parkinson disease by (18)F-9-fluoropropyl-(+)-dihydrotetrabenzazine PET.

Unlabelled: PET with (18)F-9-fluoropropyl-(+)-dihydrotetrabenzazine ((18)F-DTBZ), a novel radiotracer targeting vesicular monoamine transporter type 2 (VMAT2), has been proven as a useful imaging marker to measure dopaminergic integrity.

Methods: The aim of this study was to evaluate the capability of (18)F-DTBZ PET in detecting the monoaminergic degeneration in early Parkinson disease (PD) in vivo. Seventeen age-matched healthy subjects and 30 PD patients at early stage of disease (duration of disease ≤ 5 y) with mild and unilateral motor symptoms underwent (18)F-DTBZ PET scans.

Brain imaging of vesicular monoamine transporter type 2 in healthy aging subjects by 18F-FP-(+)-DTBZ PET.

Unlabelled: (18)F-FP-(+)-DTBZ is a novel PET radiotracer targeting vesicular monoamine transporter type 2 (VMAT2). The goal was to explore the image features in normal human brains with (18)F-FP-(+)-DTBZ as a reference of molecular landmark for clinical diagnosis in Parkinson's disease (PD) and related disorders.

Materials And Methods: A total of 22 healthy subjects (59.

The effect of PEG-5K grafting level and particle size on tumor accumulation and cellular uptake.

PEG-modified gold nanoparticles (PEG-modified GNs) with diameters of 40 nm and 70 nm were prepared to elucidate the effect of extent of PEG (M.W. 5000) grafting and particle size on tumor accumulation and cellular uptake.

EGRF conjugated PEGylated nanographene oxide for targeted chemotherapy and photothermal therapy.

Low accumulation of chemotherapeutic agent in tumor tissue and multidrug resistance (MDR) present a major obstacle to curing cancer treatment. Therefore, how to combine several therapeutics in one system is a key issue to overcome the problem. Here, we demonstrate epidermal growth factor receptor (EGFR) antibody-conjugated PEGylated nanographene oxide (PEG-NGO) to carry epirubicin (EPI) for tumor targeting and triple-therapeutics (growth signal blocking, chemotherapy, photothermal therapy) in tumor treatment.

Non-invasive synergistic treatment of brain tumors by targeted chemotherapeutic delivery and amplified focused ultrasound-hyperthermia using magnetic nanographene oxide.

The combination of chemo-thermal therapy is the best strategy to ablate tumors, but how to heat deep tumor tissues effectively without side-damage is a challenge. Here, a systemically delivered nanocarrier is designed with multiple advantages, including superior heat absorption, highly efficient hyperthermia, high drug capacity, specific targeting ability, and molecular imaging, to achieve both high antitumor efficacy and effective amplification of hyperthermia with minimal side effects.

Noninvasive imaging oral absorption of insulin delivered by nanoparticles and its stimulated glucose utilization in controlling postprandial hyperglycemia during OGTT in diabetic rats.

This work examined the feasibility of preparing a pH-responsive nanoparticle (NP) system composed of chitosan and poly(γ-glutamic acid) conjugated with ethylene glycol tetraacetic acid (γPGA-EGTA) for oral insulin delivery in diabetic rats during an oral glucose tolerance test (OGTT). OGTT has been used largely as a model to mimic the period that comprises and follows a meal, which is often associated with postprandial hyperglycemia. Based on Förster resonance energy transfer (FRET), this work also demonstrated the ability of γPGA-EGTA to protect insulin from an intestinal proteolytic attack in living rats, owing to its ability to deprive the environmental calcium.

Pharmacodynamic analysis of magnetic resonance imaging-monitored focused ultrasound-induced blood-brain barrier opening for drug delivery to brain tumors.

Microbubble-enhanced focused ultrasound (FUS) can enhance the delivery of therapeutic agents into the brain for brain tumor treatment. The purpose of this study was to investigate the influence of brain tumor conditions on the distribution and dynamics of small molecule leakage into targeted regions of the brain after FUS-BBB opening. A total of 34 animals were used, and the process was monitored by 7T-MRI.