Introduction: Intranasal (IN) administration, often referred to as nose-to-brain (N2B) drug delivery, is an attractive approach for delivering drugs to the central nervous system. However, the efficacy of this method is limited because of the small size of the nasal olfactory region, which limits the drug dosage. Using permeation enhancers could improve drug delivery from this region to the brain, though their effects are not fully understood.
View Article and Find Full Text PDFAs drug-metabolizing enzyme activities are affected by a variety of factors, such as drug-drug interactions, a method to evaluate drug-metabolizing enzyme activities in real time is needed. In this study, we developed a novel SPECT imaging probe for evaluation of hepatic CYP2D activity. Iodine-123- and 125-labeled 4-iodobenzylmequitazine (I-BMQ) was synthesized with high labeling and purity.
View Article and Find Full Text PDFUnlabelled: Cytomegalovirus (CMV), a type of herpes virus, is the predominant cause of congenital anomalies due to intrauterine infections in humans. Adverse outcomes related to intrauterine infections with human cytomegalovirus (HCMV) vary widely, depending on factors such as fetal infection timing, infection route, and viral virulence. The precise mechanism underlying HCMV susceptibility remains unclear.
View Article and Find Full Text PDFCough is known as a protective reflex to keep the airway free from harmful substances. Although brain activity during cough was previously examined mainly by functional magnetic resonance imaging (fMRI) with model analysis, this method does not capture real brain activity during cough. To obtain accurate measurements of brain activity during cough, we conducted whole-brain scans during different coughing tasks while correcting for head motion using a restraint-free positron emission tomography (PET) system.
View Article and Find Full Text PDFThe nose-to-brain (N2B) pathway has garnered attention because it transports drugs directly into the brain. Although recent studies have suggested the necessity of selective drug administration to the olfactory region for effective N2B drug delivery, the importance of delivering the formulation to the olfactory region and the detailed pathway involved in drug uptake in primates brain remain unclear. Here, we developed a combination system for N2B drug delivery comprising a proprietary mucoadhesive powder formulation and a dedicated nasal device (N2B-system) and evaluated it for nasal drug delivery to the brain in cynomolgus monkeys.
View Article and Find Full Text PDFPurpose: Near-infrared photoimmunotherapy (NIR-PIT) is a new cancer phototherapy using an antibody-photosensitizer conjugate (Ab-IR700). By NIR light irradiation, Ab-IR700 forms a water-insoluble aggregation on the plasma membrane of cancer cells, leading to lethal membrane damage of cancer cells with high selectivity. However, IR700 produces singlet oxygen, which induces non-selective inflammatory responses such as edema in normal tissues around the tumor.
View Article and Find Full Text PDFThe accumulation of radiolabeled phosphonium cations in cells is dependent on the mitochondrial membrane potential (MMP). However, the efflux of these cations from tumor cells via P-glycoprotein (P-gp) limits their clinical application as MMP-based imaging tracers. In the present study, we designed (E)-diethyl-4-[I]iodobenzyl-4-stilbenylphosphonium ([I]IDESP), which contains a stilbenyl substituent, as a P-gp inhibitor to reduce P-gp recognition, and evaluated its biological properties in comparison with 4-[I]iodobenzyl dipropylphenylphosphonium ([I]IDPP).
View Article and Find Full Text PDFDrug metabolizing enzyme activity is affected by various factors such as drug-drug interactions, and a method to quantify drug metabolizing enzyme activity in real time is needed. In this study, we developed a novel radiopharmaceutical for quantitative imaging to estimate hepatic CYP3A4 and CYP2D6 activity. Iodine-123- and 125-labeled -desmethylvenlafaxine (I-ODV) was obtained with high labeling and purity, and its metabolism was found to strongly involve CYP3A4 and CYP2D6.
View Article and Find Full Text PDFSingle-photon emission computed tomography (SPECT) imaging using intravenous radioactive ligand administration to indirectly evaluate the time-dependent effect of intranasal drugs with poor blood-brain barrier permeability on brain drug distributions in mice was evaluated. The biodistribution was examined using domperidone, a dopamine D2 receptor ligand, as the model drug, with intranasal administration at 0, 15, or 30 min before intravenous [I]IBZM administration. In the striatum, [I]IBZM accumulation was significantly lower after intranasal (IN) domperidone administration than in controls 15 min after intravenous [I]IBZM administration.
View Article and Find Full Text PDFDehydrin is an intrinsically disordered protein involved in the cold tolerance of plants. Although dehydrins have been thought to protect biomembranes under cold conditions, the underlying protective mechanism has not been confirmed. Here we report that Arabidopsis dehydrin AtHIRD11 inhibited the aggregation of phospholipid liposomes after freezing and thawing.
View Article and Find Full Text PDFIntroduction: Macrophages play a vital role in the development of atherosclerotic cardiovascular disease. Macrophages are functionally and phenotypically heterogeneous immune cells and commonly exist in two distinct or polarized subsets: pro-inflammatory M1 and anti-inflammatory M2 phenotypes. Previous reports suggest that stimulation of α7 or α4β2 nicotinic acetylcholine receptors (nAChRs) in macrophages leads to an anti-inflammatory response.
View Article and Find Full Text PDFThe positron emission tomography probes 2-deoxy-2-[F]fluoro-D-glucose ([F]FDG) and 2-tert-butyl-4-chloro-5-{6-[2-(2-[F]fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one ([F]BCPP-EF) are designed to evaluate glycolysis and oxidative phosphorylation, respectively, and are both used to estimate neuronal activity. However, previous studies have shown a discrepancy in these probes' accumulation in the compromised region, possibly due to the presence of activated microglia acting like deleterious or neuroprotective phenotypes. Hence, we evaluated lipopolysaccharide (LPS)- and interleukin 4 (IL4)-stimulated microglial uptake of [C]2DG and [F]BCPP-EF to give a new insight into the hypothesis that different uptake of [F]FDG and [F]BCPP-EF can be ascribed to the different metabolic pathways activated during microglial activation.
View Article and Find Full Text PDFVentilator-induced lung injury (VILI) can be life-threatening and it is important to prevent the development of VILI. It remains unclear whether the prone position affects neutrophilic inflammation in the lung regions in vivo, which plays a crucial role in the pathogenesis of VILI. This study aimed to assess the relationship between the use of the prone position and the development of VILI-associated regional neutrophilic lung inflammation.
View Article and Find Full Text PDFAs current treatments for multiple sclerosis (MS) remain chemotherapeutic ones directed toward symptoms, the development of a curative treatment is urgently required. Herein, we show an autoreactive immune cell-targetable approach using autoantigen-modified liposomes for the curative treatment of MS. In these experiments, experimental autoimmune encephalomyelitis (EAE) induced by autoantigenic myelin oligodendrocyte glycoprotein (MOG) peptide was used as a model of primary progressive MS, and MOG-modified liposomes encapsulating doxorubicin (MOG-LipDOX) were used as a therapeutic drug.
View Article and Find Full Text PDFBackground: Animal brain functions evaluated by in vivo imaging under anesthesia can be affected by anesthetic agents, resulting in incorrect assessment of physiological brain function. We therefore performed dynamic positron emission tomography (PET) imaging of conscious rats using recently reported soft immobilization to validate the efficacy of the immobilization for brain function assessments. We also determined the effects of six anesthetic agents-a mixed anesthetic agent (MMB), ketamine + xylazine (KX), chloral hydrate (Chloral), pentobarbital (PTB), propofol (PF), and isoflurane (IFL)-on brain function by comparison with conscious rats.
View Article and Find Full Text PDFBreast positron emission tomography (PET) has had insurance coverage when performed with conventional whole-body PET in Japan since 2013. Together with whole-body PET, accurate examination of breast cancer and diagnosis of metastatic disease are possible, and are expected to contribute significantly to its treatment planning. To facilitate a safer, smoother, and more appropriate examination, the Japanese Society of Nuclear Medicine published the first edition of practice guidelines for high-resolution breast PET in 2013.
View Article and Find Full Text PDFObjective: Iodine-131 (I-131) radioactive iodine therapy (RAI) after total thyroidectomy is the standard treatment for patients with differentiated thyroid cancer (DTC). We investigated the relationship between the quantitative parameters of the iodine uptake and the disappearance of the accumulation in the thyroid bed in adjuvant therapy using a 1.11 GBq or 3.
View Article and Find Full Text PDFObjective: Angiogenesis facilitates tumor survival and promotes malignancy. The vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) tyrosine kinase (TK) signaling pathway is a key factor mediating angiogenesis, suggesting that this pathway may be a target for diagnosis and therapy. In this study, we aimed to develop small molecule radioiodinated probes applicable for in vivo VEGFR imaging considering the versatility and usefulness of single-photon emission computed tomography (SPECT).
View Article and Find Full Text PDFTissue factor (TF), which is well known as a trigger molecule of extrinsic coagulation, is found in not only tumor cells but also in stromal cells in tumor tissues. Thus, TF is a candidate molecule to potentially enable targeting of both tumor cells and stromal cells for anti-cancer drug delivery. Herein, we prepared liposomes conjugated with the Fab' fragment of anti-TF antibody (TF Ab-Lip) and evaluated the capability for drug delivery to stroma-rich tumors for realizing a whole tumor tissue-targetable strategy.
View Article and Find Full Text PDFMonoamine oxidase B (MAO-B), predominantly expressed in glial cells, plays an important role in neurotransmitter regulation, and MAO-B activity relates to several neuronal diseases. Here, we aimed to develop a radiofluorinated MAO-B imaging probe based on the structure of a selective MAO-B inhibitor, MD-230254. We synthesized and evaluated a series of compounds in vitro and in vivo.
View Article and Find Full Text PDFThe development of atherosclerotic plaques is a critical step that can result in an arterial embolism. Therefore, detection of these vulnerable plaques is of clinical significance for the diagnosis of atherosclerosis. However, there are few imaging systems able to detect such plaques easily.
View Article and Find Full Text PDFThe antineoplastic agent oxaliplatin is a first-line treatment for colorectal cancer. However, neuropathic pain, characterized by hypersensitivity to cold, emerges soon after treatment. In severe instances, dose reduction or curtailing treatment may be necessary.
View Article and Find Full Text PDFTriglyceride deposit cardiomyovasculopathy (TGCV) is an intractable cardiovascular disease for which a specific treatment is urgently required. In TGCV, adipose triglyceride lipase (ATGL) deficiency results in the abnormal intracellular metabolism of long-chain fatty acid (LCFA) which leads to TG deposition. Medium-chain triglycerides have been used as an important functional food for various human diseases.
View Article and Find Full Text PDFObjectives: The purpose of this study is the development of novel fluorine-18-fluorodeoxyglucose (F-FDG)-PET and Tc-hexamethylpropylene amine oxime (HMPAO) SPECT methods with free-moving apparatus on conscious rats to investigate brain activity without the effects of anesthesia and tactual stimulation. We also assessed the sensitivity of the experimental system by an intervention study using fluoxetine as a reference drug.
Materials And Methods: A catheter was inserted into the femoral vein and connected to a free-moving cannula system.
Background: Cerebral blood flow (CBF) quantitation using technetium-99m hexamethylpropyleneamine oxime (Tc-HMPAO) generally requires assessment of input function by arterial blood sampling, which would be invasive for small animals. We therefore performed chest dynamic planar imaging, instead of arterial blood sampling, to estimate the input function and establish noninvasive quantitation method of rat CBF using the image-derived input function.
Results: Integrated radioactivity concentration in the heart-blood pool on planar images (AUC-planar) was identical to that in arterial blood samples (AUC-sampling).