New liposome-radionuclide-chelate combination for tumor targeting and rapid healthy tissue clearance.

Radionuclide imaging and therapy are promising methods for controlling systemic cancers; however, their clinical application has been limited by excessive radionuclide accumulation in healthy tissues. To minimize radionuclide accumulation in non-cancerous tissues while ensuring sufficient build up in tumors, we aimed to develop a method that controlled the in vivo dynamics of radionuclides post-administration. To this end, we describe a novel strategy that combines liposomes, a potent carrier system for drug delivery, with unique radionuclide-ligand complexes based on In-ethylenedicysteine.

Simultaneous visualization of multiple radionuclides in vivo.

The insufficient energy and spatial resolutions of radionuclide imaging with conventional scintillation detectors restrict the visualization of multiple radionuclides and of microstructures in tissue. Here we report the development and performance of an imaging system equipped with a cadmium telluride diode detector that achieves an energy resolution of 1.7% at 140 keV and a spatial resolution of 250 μm.

Novel method for screening functional antibody with comprehensive analysis of its immunoliposome.

Development of monoclonal antibody is critical for targeted drug delivery because its characteristics determine improved therapeutic efficacy and reduced side-effect. Antibody therapeutics target surface molecules; hence, internalization is desired for drug delivery. As an antibody-drug conjugate, a critical parameter is drug-to-antibody ratio wherein the quantity of drugs attached to the antibody influences the antibody structure, stability, and efficacy.

Functional Characterization of VEGF- and FGF-induced Tumor Blood Vessel Models in Human Cancer Xenografts.

Background/aim: Tumor angiogenesis induced by vascular endothelial growth factor (VEGF) and/or fibroblast growth factor (FGF) plays an important role in tumor growth, metastasis, and drug resistance. However, the characteristics of tumor vessels derived from these angiogenic factors have not been fully explored.

Materials And Methods: To functionally examine tumor vessels, we developed in vivo VEGF- and FGF-induced tumor blood vessel models.

Antitumor effects of eribulin depend on modulation of the tumor microenvironment by vascular remodeling in mouse models.

We previously reported that eribulin mesylate (eribulin), a tubulin-binding drug (TBD), could remodel tumor vasculature (i.e. increase tumor vessels and perfusion) in human breast cancer xenograft models.

Radiolabeled liposome imaging determines an indication for liposomal anticancer agent in ovarian cancer mouse xenograft models.

Liposomal anticancer agents can effectively deliver drugs to tumor lesions, but their therapeutic effects are enhanced in only limited number of patients. Appropriate biomarkers to identify responder patients to these liposomal agents will improve their treatment efficacies. We carried out pharmacological and histopathological analyses of mouse xenograft models bearing human ovarian cancers (Caov-3, SK-OV-3, KURAMOCHI, and TOV-112D) to correlate the therapeutic effects of doxorubicin-encapsulated liposome (Doxil(®) ) and histological characteristics linked to the enhanced permeability and retention effect.

Novel Indocyanine Green-Phytate Colloid Technique for Sentinel Node Detection in Head and Neck: Mouse Study.

Objective: Sentinel node navigation surgery using real-time, near-infrared imaging with indocyanine green is becoming popular by allowing head and neck surgeons to avoid unnecessary neck dissection. The major drawback of this method is its quick migration through the lymphatics, limiting the diagnostic time window and undesirable detection of downstream nodes. We resolved this problem by mixing indocyanine green (ICG) with phytate colloid to retard its migration and demonstrated its feasibility in a nude mouse study.

Development of 111In-labeled liposomes for vulnerable atherosclerotic plaque imaging.

Unlabelled: Macrophage infiltration is a common characteristic feature of atherosclerotic-vulnerable plaques. Macrophages recognize phosphatidylserine (PS) exposed on the surface of apoptotic cells, which triggers the engulfment of the apoptotic cells by macrophages through phagocytosis. In this study, we prepared radiolabeled PS liposomes for detection of vulnerable plaques.

In vivo visualization of heterogeneous intratumoral distribution of hypoxia-inducible factor-1α activity by the fusion of high-resolution SPECT and morphological imaging tests.

Purpose: We aimed to clearly visualize heterogeneous distribution of hypoxia-inducible factor 1α (HIF) activity in tumor tissues in vivo.

Methods: We synthesized of (125)I-IPOS, a (125)I labeled chimeric protein probe, that would visualize HIF activity. The biodistribution of (125)I-IPOS in FM3A tumor-bearing mice was evaluated.

In vivo SPECT imaging with 111In-DOTA-c(RGDfK) to detect early pancreatic cancer in a hamster pancreatic carcinogenesis model.

Unlabelled: Early detection of pancreatic cancer is key to overcoming its poor prognosis. α(v)β(3)-integrin is often overexpressed in pancreatic tumor cells, whereas it is scarcely expressed in normal pancreatic cells. In this study, we investigated the usefulness of SPECT imaging with (111)In-1,4,7,10-tetraazacylododecane-N,N',N″,N'''-tetraacetic acid-cyclo-(Arg-Gly-Asp-d-Phe-Lys) [(111)In-DOTA-c(RGDfK)], an imaging probe of α(v)β(3)-integrin, for the early detection of pancreatic cancer in a hamster pancreatic carcinogenesis model.

Synthesis and evaluation of a novel (99m)Tc-labeled bioreductive probe for tumor hypoxia imaging.

Tumor hypoxia is closely associated with the malignant progression and/or the high metastatic ability of tumors and often induces resistance to chemo- and/or radiotherapy. Thus, the detection and evaluation of hypoxia is important for the optimization of cancer therapy. We designed a novel (99m)Tc-labeled probe for tumor hypoxia imaging that utilizes bioreductive reactions in hypoxic cells.

High resolution SPECT imaging for visualization of intratumoral heterogeneity using a SPECT/CT scanner dedicated for small animal imaging.

Objectives: Tumor interiors are never homogeneous and in vivo visualization of intratumoral heterogeneity would be an innovation that contributes to improved cancer therapy. But, conventional nuclear medicine tests have failed to visualize heterogeneity in vivo because of limited spatial resolution. Recently developed single photon emission computed tomographic (SPECT) scanners dedicated for small animal imaging are of interest due to their excellent spatial resolution of <1 mm, but few studies have focused on the evaluation of intratumoral heterogeneity.

Evaluation of [125I]IPOS as a molecular imaging probe for hypoxia-inducible factor-1-active regions in a tumor: comparison among single-photon emission computed tomography/X-ray computed tomography imaging, autoradiography, and immunohistochemistry.

To image hypoxia-inducible factor-1 (HIF-1)-active tumors, we previously developed a chimeric protein probe ([(123/125) I]IPOS) that is degraded in the same manner as HIF-1α under normoxic conditions. In the present study, we aim to show that the accumulation of radioiodinated POS reflects the expression of HIF-1. In vivo single-photon emission computed tomography (SPECT)/X-ray CT (CT) imaging, autoradiography, and double-fluorescent immunostaining for HIF-1α and pimonidazole (PIMO) were carried out 24 h after the injection of [(125) I]IPOS.

Segmental acquisition method for stationary objects in (18)F-fluorodeoxyglucose positron emission tomography tests.

Purpose: We investigated whether images of stationary objects obtained by segmental acquisition with positron emission tomography using 2-deoxy-2-[(18)F]-fluoro-D: -glucose (FDG-PET) are of a quality equivalent to those obtained by conventional continuous acquisition.

Materials And Methods: Phantoms filled with FDG and mid-abdominal regions of 18 patients who underwent FDG-PET tests were imaged by both continuous and segmental acquisition methods. The total acquisition time was set to 3 min; in the segmental acquisition mode, imaging for 15 s was repeated 12 times.

Effects of aging and every-other-day feeding on the levels of oxygen radicals in rat brain slices.

Caloric and food restriction attenuate oxidative stress. The effect of aging and every-other-day (EOD) feeding on oxygen radical-dependent chemiluminescent intensity was examined in ex vivo brain slices from Fischer rats during oxygenation and hypoxia-reoxygenation with lucigenin, a chemilumigenic probe used for detecting superoxide anion radicals. The chemiluminescent intensity increased during reoxygenation after hypoxic treatment, and the chemiluminescence in the brain slices at the baseline and during reoxygenation increased with age.

5-S-GAD, a novel radical scavenging compound, prevents lens opacity development.

The ability of N-beta-alanyl-5-S-glutathionyl-3,4-dihydroxyphenylalanine (5-S-GAD)-a novel catechol derivative isolated from an insect as an antibacterial substance-to scavenge free radicals and prevent cataract progression was examined. 5-S-GAD scavenged 1,1-diphenylpicrylhydrazyl (DPPH) and superoxide anions (O(2)(*)(-)), and inhibited lipid peroxidation. It also significantly inhibited the onset of glucocorticoid-induced lens opacification in chick embryos.

Inhibition of glucocorticoid-induced cataracts in chick embryos by RU486: a model for studies on the role of glucocorticoids in development.

Cataract formation can be induced by glucocorticoid treatment of developing chick embryos. We show here that this response can be blocked very effectively by use of the antiglucocorticoid RU486. When dexamethasone (0.

Predominant phosphatase in the ocular lens regulated by physiological concentrations of magnesium and calcium.

A magnesium-dependent phosphatase with a molecular weight of about 55 kDa was found in the lens of chicken embryo, mouse, rabbit and bovine. It appears to be unique to the lens and, when activated by magnesium, accounts for the majority of the phosphatase activity in the lens. Phosphatases in the lens were separated by using high-resolution gel permeation column chromatography, and phosphatase activity was determined with p-nitrophenyl phosphate (pNPP) as a substrate.