The effects of repeated brain MRI on chromosomal damage.

Background: Magnetic resonance imaging (MRI) is currently considered a safe imaging technique because, unlike computed tomography, MRI does not expose patients to ionising radiation. However, conflicting literature reports possible genotoxic effects of MRI. We herein examine the chromosomal effects of repeated MRI scans by performing a longitudinal follow-up of chromosomal integrity in volunteers.

Imaging the aging brain: study design and baseline findings of the SENIOR cohort.

Background: Current demographic trends point towards an aging society entailing increasing occurrence and burden of neurodegenerative diseases. In this context, understanding physiological aging and its turning point into neurodegeneration is essential for the development of possible biomarkers and future therapeutics of brain disease.

Methods: The SENIOR study represents a longitudinal, observational study including cognitively healthy elderlies aged between 50 and 70 years old at the time of inclusion, being followed annually over 10 years.

Validation of in vitro cell-based human blood-brain barrier model using clinical positron emission tomography radioligands to predict in vivo human brain penetration.

We have evaluated a novel in vitro cell-based human blood-brain barrier (BBB) model that could predict in vivo human brain penetration for compounds with different BBB permeabilities using the clinical positron emission tomography (PET) data. Comparison studies were also performed to demonstrate that the in vitro cell-based human BBB model resulted in better predictivity over the traditional permeability model in discovery organizations, Caco-2 cells. We evaluated the in vivo BBB permeability of [(18)F] and [(11)C]-compounds in humans by PET imaging.

Spatiotemporal decomposition in object-space along reconstruction in emission tomography.

Emission tomography has provided a new insight in brain mechanisms past years. Although reconstructions are nowadays mostly static, trend is going toward dynamic acquisitions and reconstructions. This opens a new range of investigations, for instance for drugs discovery.

Guideline to regulations for radiopharmaceuticals in early phase clinical trials in the EU.

The purpose of this guideline is to help investigators by giving an overview of relevant current EU requirements concerning the quality of starting materials and final drug products (the radiopharmaceuticals), the non-clinical safety studies and dosimetry considerations whilst designing a human clinical trial which includes the use of radiopharmaceutical compounds.

Predicting plutonium decorporation efficacy after intravenous administration of DTPA formulations: Study of pharmacokinetic-pharmacodynamic relationships in rats.

Purpose: The objectives of this study were: 1) to assess the relationship between plutonium decorporation (increased excretion and reduced retention in main organs of deposition) induced by intravenous liposome formulations of the chelating agent diethylene triamine pentaacetic acid (DTPA) and its pharmacokinetics, and 2) to model the renal excretion of plutonium after treatment with liposome-encapsulated DTPA in order to predict its efficacy and to optimise treatment schedules.

Materials And Methods: Pharmacokinetic parameters from plasma or urinary data (days 0-16 sample collections) were modelled versus decorporation efficacy, and best correlations were selected for their goodness of fit.

Results: The plutonium decorporation enhancement by DTPA liposomal formulations was well described by logistic models and the best correlation was observed with the area under the DTPA concentration curve of each formulation.

Pharmacokinetics of DTPA entrapped in conventional and long-circulating liposomes of different size for plutonium decorporation.

The aim of the present study was to develop an efficient DTPA liposome formulation designed for plutonium decorporation. DTPA was encapsulated in conventional (CL) and polyethylene glycol-coated stealth liposomes (SL) prepared by extrusion followed by the freeze-thawing method and sizing from around 100 to 800 nm. DTPA encapsulation percentages were approximately 30% in CL of any size but dropped from 48% to 7% as the diameter of SL was reduced.

In vivo imaging of human cerebral nicotinic acetylcholine receptors with 2-18F-fluoro-A-85380 and PET.

Unlabelled: 2-(18)F-fluoro-3-[2(S)-2-azetidinylmethoxy]pyridine (2-(18)F-fluoro-A-85380) is a PET radioligand that is specific for nicotinic acetylcholine receptors (nAChRs) and has a high affinity for the alpha(4)beta(2) subtype. The purpose of this study was to evaluate different strategies to quantify 2-(18)F-fluoro-A-85380 binding in healthy nonsmoking human volunteers.

Methods: After intravenous injection of 189 +/- 30 MBq (0.

Early detection of chemoresistance in vivo through the use of a radiolabeled antisense oligonucleotide.

Aims: Radiolabeled antisense oligonucleotide to target the mRNA of the hmdr1 gene for diagnostic purposes is a new concept for evaluating the chemoresistance of tumors in vivo.

Methods And Results: An 18 mer complementary to the zone which contains the translation initiation codon of the hmdr1 gene was modified using one phosphoramidate group and one dimethoxytrityle group at the 5' and 3'ends. It permitted probe radiolabeling by 125I.

Characterization of a synthetic anionic vector for oligonucleotide delivery using in vivo whole body dynamic imaging.

Purpose: To compare the pharmacokinetics and bioavailability of an oligonucleotide delivered in a free form or using cationic or anionic synthetic carrier systems.

Methods: Whole body dynamic quantitative imaging and metabolism of a HIV antisense oligonucleotide intravenously administered either free or incorporated into synthetic carriers were compared in baboons. using non invasive positron emission tomography and an enzyme-based competitive hybridization assay, respectively.

Anti-cancer drug diffusion within living rat brain tissue: an experimental study using [3H](6)-5-fluorouracil-loaded PLGA microspheres.

This study was performed (i) to monitor the diffusion of the anti-cancer drug 5-fluorouracil (5-FU) and (ii) to elucidate the fate of poly(lactide-co-glycolide) (PLGA) based microspheres within living rat brain tissue upon intracranial implantation. Drug-loaded microparticles were prepared using a solvent emulsion/extraction process and administered into healthy and C6 glioma-bearing Sprague-Dawley rats. The same surgical procedure was carried out with magnetite-loaded microspheres.

Intravitreal delivery of oligonucleotides by sterically stabilized liposomes.

Purpose: The efficacy of sterically stabilized liposomes for delivering a model phosphodiester oligonucleotide intravitreally was investigated in the rabbit.

Methods: Ocular distribution and clearance from the vitreous humor of a model 16-mer oligothymidylate (pdT16) were evaluated in the rabbit by radioactivity measurements after intravitreal injection of either a solution or liposomes containing the [33P]pdT16 oligonucleotide. The integrity of pdT16 was investigated using a competitive hybridization assay.