Development and Evaluation of the Magnetic Properties of a New Manganese (II) Complex: A Potential MRI Contrast Agent

Magnetic resonance imaging (MRI) is a non-invasive powerful modern clinical technique that is extensively used for the high-resolution imaging of soft tissues. To obtain high-definition pictures of tissues or of the whole organism this technique is enhanced by the use of contrast agents. Gadolinium-based contrast agents have an excellent safety profile. However, over the last two decades, some specific concerns have surfaced. Mn(II) has different favorable physicochemical characteristics and a good toxicity profile, which makes it a good alternative to the Gd(III)-based MRI contrast agents currently used in clinics. Mn(II)-disubstituted symmetrical complexes containing dithiocarbamates ligands were prepared under a nitrogen atmosphere. The magnetic measurements on Mn complexes were carried out with MRI phantom measurements at 1.5 T with a clinical magnetic resonance. Relaxivity values, contrast, and stability were evaluated by appropriate sequences. Studies conducted to evaluate the properties of paramagnetic imaging in water using a clinical magnetic resonance showed that the contrast, produced by the complex [Mn(II)(L’)2] × 2H2O (L’ = 1.4-dioxa-8-azaspiro[4.5]decane-8-carbodithioate), is comparable to that produced by gadolinium complexes currently used in medicine as a paramagnetic contrast agent

Synthesis, characterization and antiproliferative activity of amino- and DMSO complexes of platinum(II) containing L-carnitine.

L-Carnitine, a biomolecule able to cross the blood-brain barrier exploiting specific transporters, behaves as mono or bidentate anionic ligand for Pt(II) in the new amino complexes cis-[Pt(L-carnitine-O)2(NH3)2](BF4)2 (1), cis-[PtCl(L-carnitina-O)(NH3)2]BF4 (2), [Pt(L-carnitine-O,O’)(1,2-DACH)]BF4 (3), [Pt(L-carnitine-O)2(1,2-DACH)](BF4)2 (4), and [PtCl(L-carnitine-O)(1,2-DACH)](BF4) (5). Four complexes with DMSO have been also prepared and characterized: the synthetic intermediate [Pt(CO3)(DMSO)2] (6), [Pt(L-carnitine-O,O’)(DMSO)2]BF4 (7), cis-[Pt(L-carnitine-O)2(DMSO)2](BF4)2 (8) and cis-[PtCl(L-carnitine-O)(DMSO)2]BF4, (9). The antiproliferative activity of three representative complexes 1, 5 and 7 has been assayed against three human cancer cell lines A2780, K562 and SKOV3, and it was found comparable to that of the parent active compounds cis-[PtCl2(1,2-DACH)] and cisplati

Structural features of the intermolecular interactions between PTA and nutraceutical acids in salts and platinum complexes

The cage-like phosphine 1,3,5-triaza-7-phosphaadamantane (PTA) is attracting a lot of attention in coordination chemistry due to its favorable properties like stability to oxidation, small dimensions, solubility in water. Actually, Ru, Pd, Pt, Au,Ag complexes containing PTA are under investigation for aqueous phase or biphasic homogeneous catalysis, anticancer activity, photoluminescence experiments as well as crystal engineering. PTA molecule has a basic character, and it undergoes a selective nitrogen protonation, while the preferred coordination site is phosphorus. However, unlike the related compound hexamethylenetetramine, PTA salts have been reported so far. We have therefore undertaken a systematic synthetic-structural study on PTA- nutraceutical acids salts, aimed at exploring the structural features of the interactions between the different molecules

Polytopic carriers for platinum ions: from digalloyl depside to tannic acid

A novel dinuclear platinum(II) complex, namely [Pt2m-GG(Me2SO-S)4] (8, GG = deprotonated methyl digallate), was easily synthesized under solvent-free conditions by grinding a solid m/p digalloyl depside with the Pt precursor [PtCO3(Me2SO-S)2]. Similarly, platinum nuclei were introduced into the galloyl chains of tannic acid (TA). In particular, three complexes A, B and C were prepared by reacting TA as a polytopic ligand with an increasing amount of [PtCO3(Me2SO-S)2]. The antiproliferative activity of complexes 8, A, B and C together with the corresponding ligands GG and TA was tested in vitro and compared with that of cisplatin on two human tumor cell lines, A2780 (ovarian cisplatin-sensitive) and A2780cis (ovarian cisplatin-resistant), and one non-tumoral cell line, HaCat. The experiments focusing on their pro-apoptotic activity indicated that the antiproliferative activity of the most active Pt(II) complexes is associated with the induction of apoptosis

Highly Efficient Micro-Scale Liquid-Liquid In-Flow Extraction of 99mTc from Molybdenum

The trend to achieve even more compact-sized systems is leading to the development of micro-scale reactors (lab-on-chip) in the field of radiochemical separation and radiopharmaceutical production. Technetium-99m extraction from both high and low specific activity molybdenum could be simply performed by MEK-driven solvent extraction if it were not for unpractical automation. The aim of this work is to develop a solvent extraction and separation process of technetium from molybdenum in a micro-scale in-flow chemistry regime with the aid of a capillary loop and a membrane-based separator, respectively. The developed system is able to extract and separate quantitatively and selectively (91.0 ± 1.8% decay corrected) the [99mTc]TcO4Na in about 20 min, by using a ZAIPUT separator device. In conclusion, we demonstrated for the first time in our knowledge the high efficiency of a MEK-based solvent extraction process of 99mTc from a molybdenum-based liquid phased in an in-flow micro-scale regime

Technetium-99m Radiopharmaceuticals for Ideal Myocardial Perfusion Imaging: Lost and Found Opportunities

The favorable nuclear properties in combination with the rich coordination chemistry make technetium-99m the radioisotope of choice for the development of myocardial perfusion tracers. In the early 1980s, [99mTc]Tc-Sestamibi, [99mTc]Tc-Tetrofosmin, and [99mTc]Tc-Teboroxime were approved as commercial radiopharmaceuticals for myocardial perfusion imaging in nuclear cardiology. Despite its peculiar properties, the clinical use of [99mTc]Tc-Teboroxime was quickly abandoned due to its rapid myocardial washout. Despite their widespread clinical applications, both [99mTc]Tc-Sestamibi and [99mTc]Tc-Tetrofosmin do not meet the requirements of an ideal perfusion imaging agent due to their relatively low first-pass extraction fraction and high liver absorption. An ideal radiotracer for myocardial perfusion imaging should have a high myocardial uptake; a high and stable target-to-background ratio with low uptake in the lungs, liver, stomach during the image acquisition period; a high first-pass myocardial extraction fraction and very rapid blood clearance; and a linear relationship between radiotracer myocardial uptake and coronary blood flow. Although it is difficult to reconcile all these properties in a single tracer, scientific research in the field has always channeled its efforts in the development of molecules that are able to meet the characteristics of ideality as much as possible. This short review summarizes the developments in 99mTc myocardial perfusion tracers, which are able to fulfill hitherto unmet medical needs and serve a large population of patients with heart disease, and underlines their strengths and weaknesses, the lost and found opportunities thanks to the developments of the new ultrafast SPECT technologies