Determination of total silicon and SiO2 particles using an ICP-MS based analytical platform for toxicokinetic studies of synthetic amorphous silica

Synthetic amorphous silica (SAS), manufactured in pyrogenic or precipitated form, is a nanomaterial with a widespread use as food additive (E 551). Oral exposure to SAS results from its use in food and dietary supplements, pharmaceuticals and toothpaste. Recent evidence suggests that oral exposure to SAS may pose health risks and highlights the need to address the toxic potential of SAS as affected by the physicochemical characteristics of the different forms of SAS. For this aim, investigating SAS toxicokinetics is of crucial importance and an analytical strategy for such an undertaking is presented. The minimization of silicon background in tissues, control of contamination (including silicon release from equipment), high-throughput sample treatment, elimination of spectral interferences affecting inductively coupled plasma mass spectrometry (ICP-MS) silicon detection, and development of analytical quality control tools are the cornerstones of this strategy. A validated method combining sample digestion with silicon determination by reaction cell ICP-MS is presented. Silica particles are converted to soluble silicon by microwave dissolution with mixtures of HNO3, H2 O2 and hydrofluoric acid (HF), whereas interference-free ICP-MS detection of total silicon is achieved by ion-molecule chemistry with limits of detection (LoDs) in the range 0.2–0.5 µg Si g−1 for most tissues. Deposition of particulate SiO2 in tissues is assessed by single particle ICP-MS

Topics on General and Formal Ontology (E-book)

The essays collected in this book deal with a) general ontology basically in two meanings: as a philosophical discipline that studies \u201cbeing\u201d, that is as a part of metaphysics, and as a theory that deals with types of entities, specifically those types of abstract entities that are allowed in a language (ontology as specification of a conceptualization), and b) formal ontology both as a \u201ccategorial ontology\u201d and as a formalized discipline that represents an \u201contological\u201d part of the varied world of formal disciplines. This collection introduces the work of researchers from Europe, Middle-East, United States, Canada and Australia. Papers ranges across many topics of contemporary inquiry in ontology: foundations of ontology, primary relations (identity and identification), mereology, ontology of physical entities, trope ontology, modality and ontological imports of logic and theory of truth

Topics on General and Formal Ontology (Press)

The essays collected in this book deal with a) general ontology basically in two meanings: as a philosophical discipline that studies \u201cbeing\u201d, that is as a part of metaphysics, and as a theory that deals with types of entities, specifically those types of abstract entities that are allowed in a language (ontology as specification of a conceptualization), and b) formal ontology both as a \u201ccategorial ontology\u201d and as a formalized discipline that represents an \u201contological\u201d part of the varied world of formal disciplines. This collection introduces the work of researchers from Europe, Middle-East, United States, Canada and Australia. Papers range across many topics of contemporary inquiry in ontology: foundations of ontology, primary relations (identity and identification), mereology, ontology of physical entities, trope ontology, modality and ontological imports of logic and theory of truth

First clinical study of a pegylated diabody I-124-labeled PEG-AVP0458 in patients with tumor-associated glycoprotein 72 positive cancers

Through protein engineering and a novel pegylation strategy, a diabody specific to tumor-associated glycoprotein 72 (TAG-72) (PEG-AVP0458) has been created to optimize pharmacokinetics and bioavailability to tumor. We report the preclinical and clinical translation of PEG-AVP0458 to a first-in-human clinical trial of a diabody. Methods: Clinical translation followed characterization of PEG-AVP0458 drug product and preclinical biodistribution and imaging assessments of Iodine-124 trace labeled PEG-AVP0458 (124I-PEG-AVP0458). The primary study objective of the first-in-human study was the safety of a single protein dose of 1.0 or 10 mg/m2 124I-PEG-AVP0458 in patients with TAG-72 positive relapsed/ metastatic prostate or ovarian cancer. Secondary study objectives were evaluation of the biodistribution, tumor uptake, pharmacokinetics and immunogenicity. Patients were infused with a single-dose of 124I labeled PEG-AVP0458 (3-5 mCi (111-185 MBq) for positron emission tomography (PET) imaging, performed sequentially over a one-week period. Safety, pharmacokinetics, biodistribution, and immunogenicity were assessed up to 28 days after infusion. Results: PEG-AVP0458 was radiolabeled with 124I and shown to retain high TAG-72 affinity and excellent targeting of TAG-72 positive xenografts by biodistribution analysis and PET imaging. In the first-in-human trial, no adverse events or toxicity attributable to 124I-PEG-AVP0458 were observed. Imaging was evaluable in 5 patients, with rapid and highly specific targeting of tumor and minimal normal organ uptake, leading to high tumor:blood ratios. Serum concentration values of 124I-PEG-AVP0458 showed consistent values between patients, and there was no significant difference in T½α and T½β between dose levels with mean (± SD) results of T½α = 5.10 ± 4.58 hours, T½β = 46.19 ± 13.06 hours. Conclusions: These data demonstrates the safety and feasibility of using pegylated diabodies for selective tumor imaging and potential delivery of therapeutic payloads in cancer patients