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Gadolinium (III) complexes are under intense scrutiny as contrast agents for magnetic resonance imaging. Although currently used mainly as extracellular agents, there is a growing interest to exploit their contrast enhancing ability in the intracellular environment. To ascertain the preservation of their chemical integrity upon the intracellular entrapment, it is necessary to have a method for their dosage in the cell lysates. Herein, a mass spectrometric method for detection and quantification of gadolinium complexes in cell lysates is reported. The detection by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was carried out by using a non-acidic matrix (2,4,6-trihydroxyacetophenone), which does not allow any leakage of gadolinium from the complex. Quantification has been possible by using as an internal standard an ytterbium complex with the same ligand of the analyte. Ytterbium was chosen because, among the lanthanides, it is the one with the isotopic distribution pattern the most similar to that of gadolinium. Sensitivity was enough to detect low micromolar quantities of a cationic complex and high micromolar quantities of a neutral complex in cell lysates of rat hepatoma cells. In the case of anionic complexes, sensitivity was too low for quantitative analysis. To the best of our knowledge, this is the first report concerning the quantification of metal complexes by MALDI-TOF-MS.

A novel method of synthesizing three pyridine-containing triaza macrocycle triacetate ligands was developed using 2,6-bis(chloromethyl)pyridine in anhydrous acetonitrile as the starting material. Lanthanide(III) ions elicited different coordination abilities from the acetate pendant arms. The number of carbon atoms in the macrocyclic ring producing ligands determined the diversity of the three systems. Water relaxation rates indicated that the ring size was found to be inversely related to the degree of the hydration state.

1H Fast-Field Cycling NMR relaxometry is proposed as a powerful method to investigate tumour cell metabolism by measuring changes in cell water content and mobility across the cellular membrane. Measurements of intracellular water residence time in cultured cells were carried out by measuring T1 at fixed field (0.2 T) after the addition of a paramagnetic Gd complex (Prohance) at different concentrations in the external medium. Investigations on tumour cells (mammary adenocarcinoma TS/A) grown in normo- or hypoxic conditions or suspended in 'hypo-osmotic' solutions allowed us to demonstrate that both hypoxic and hypo-osmotic conditions cause a marked increase in water mobility as assessed by the elongation of T1. Conversely, the metabolic change caused by glutamine (an aminoacid essential for tumour growth) deprivation caused a water mobility decrease (shorter T1). These findings suggest that T1 measurements at low and variable magnetic field strengths, giving access to the assessment of intracellular water lifetime, can provide important information about tumour cell metabolism in real time and non-invasively. [ABSTRACT FROM AUTHOR]

Recently, nanoscale stimuli-responsive devices have received much attention thanks to their potential to limit the cytotoxic effect of the therapeutic treatment at the diseased tissue. Among different physical triggers, large alternating magnetic fields enable the conversion of magnetic energy into heat by using magnetic nanoparticles that generate localized hyperthermia, named Magneto Fluid Hyperthermia (MFH). This methodology can be exploited for cancer therapy or/and thermally activated drug release. The small size iron oxide nanoparticles (Fe-NPs), such as SPIO (small iron oxide particles) and USPIO (ultra-small iron oxide particles), currently used for this application have many limitations due to their 1) high intratumor concentration needed due to the low heating power 2) short particle blood-half-life, 3) non-specific distribution, 4) low internalization efficiency. For these reasons many efforts are necessary to make magneto fluid particle hyperthermia (MFH) a competitive tumor therapy for clinical applications. New iron oxide nanoparticles, coated with oleate, with a diameter of 5-18 nm, have been prepared by co-precipitation and incorporated into PLGA-NPs (PLGA=Poly(lactic-co-glycolic acid) in order to improve their biocompatibility and "in vivo" stability. Moreover, PLGA-NPs have been loaded with both NPs-Fe and antitumor drugs (Paclitaxel, PTX), an anticancer hydrophobic drug used in the treatment of ovarian and breast cancer, to perform MFH triggered drug release. The PTX and Fe-NPs loaded nanoparticles may be considered as an effective anticancer drug delivery system for Imaging-guided hyperthermic treatment of tumors. [ABSTRACT FROM AUTHOR]

Targeted imaging requires site-specific accumulation of a contrast agent (CA), and the properties of that agent must be selected according to the abundance of the target to obtain a signal above the detection limit of the instrument. However, numerical estimates of receptors per cell are rarely found in the literature. Integrin receptors would be particularly promising targets because of their accessibility from the blood stream and expression on activated neovascular endothelial cells. We systematically estimated the number of integrin receptors of cell lines and primary cells by flow cytometry analysis. Since integrin receptors are heterodimeric molecules, and αv forms complexes with various β subunits, the numbers of αv and β3 subunits are therefore dissimilar. The observed values are 3 · 103-1.4 · 104/cell for αv, and 5.3 · 102-1.1 · 104/cell for β3. Despite the low number of exposed receptors, we show that up to single-cell MR visualization can be achieved with the use of iron oxide beads complexed with antibodies as CAs. Magn Reson Med, 2006. © 2006 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Simple Summary: Glioblastoma multiforme (GBM) is one of the most common malignant brain tumors. Although a variety of GBMs is initially susceptible to chemotherapy, the development of multi-drug resistance and recurrence is frequent. Therefore, there is an urgent need for more efficient treatment modalities for GBM. Boron neutron capture therapy (BNCT) is a cancer therapy based on the potential of 10B atoms to produce α particles that cross tissues in which the 10B accumulates without damaging the surrounding healthy tissues after irradiation with low energy thermal neutrons. The aim of our study was to assess that the sodium salt of cobaltabis(dicarbollide) and its di-iodinated derivative could be good candidates for dual anti-cancer treatment (chemotherapy + BNCT). Our results strongly suggest that these small molecules, in particular [8,8′-I2-o-COSAN]−, are serious candidates to be taken into account for BNCT now that the accelerator-based neutron source facilities are more accessible, providing an alternative treatment for resistant glioblastoma. Purpose: The aim of our study was to assess if the sodium salt of cobaltabis(dicarbollide) and its di-iodinated derivative (Na[o-COSAN] and Na[8,8′-I2-o-COSAN]) could be promising agents for dual anti-cancer treatment (chemotherapy + BNCT) for GBM. Methods: The biological activities of the small molecules were evaluated in vitro with glioblastoma cells lines U87 and T98G in 2D and 3D cell models and in vivo in the small model animal Caenorhabditis elegans (C. elegans) at the L4-stage and using the eggs. Results: Our studies indicated that only spheroids from the U87 cell line have impaired growth after treatment with both compounds, suggesting an increased resistance from T98G spheroids, contrary to what was observed in the monolayer culture, which highlights the need to employ 3D models for future GBM studies. In vitro tests in U87 and T98G cells conclude that the amount of 10B inside the cells is enough for BNCT irradiation. BNCT becomes more effective on T98G after their incubation with Na[8,8′-I2-o-COSAN], whereas no apparent cell-killing effect was observed for untreated cells. Conclusions: These small molecules, particularly [8,8′-I2-o-COSAN]−, are serious candidates for BNCT now that the facilities of accelerator-based neutron sources are more accessible, providing an alternative treatment for resistant glioblastoma. [ABSTRACT FROM AUTHOR]