Improved synthesis of DA364, an NIR fluorescence RGD probe targeting αvß3 integrin.

Optical imaging (OI) is gaining increasing attention in medicine as a non-invasive diagnostic imaging technology and as a useful tool for image-guided surgery. OI exploits the light emitted in the near-infrared region by fluorescent molecules able to penetrate living tissues. Cyanines are an important class of fluorescent molecules and by their conjugation to peptides it is possible to achieve optical imaging of tumours by selective targeting. We report here the improvements obtained in the synthesis of DA364, a small fluorescent probe (1.5 kDa) prepared by conjugation of pentamethine cyanine Cy5.5 to an RGD peptidomimetic, which can target tumour cells overexpressing integrin αvß3 receptors.

Fe(deferasirox)2: An Iron(III)-Based Magnetic Resonance Imaging T1 Contrast Agent Endowed with Remarkable Molecular and Functional Characteristics.

The search for alternatives to Gd-containing magnetic resonance imaging (MRI) contrast agents addresses the field of Fe(III)-bearing species with the expectation that the use of an essential metal ion may avoid the issues raised by the exogenous Gd. Attention is currently devoted to highly stable Fe(III) complexes with hexacoordinating ligands, although they may lack any coordinated water molecule. We found that the hexacoordinated Fe(III) complex with two units of deferasirox, a largely used iron sequestering agent, owns properties that can make it a viable alternative to Gd-based agents. Fe(deferasirox)2 displays an outstanding thermodynamic stability, a high binding affinity to human serum albumin (three molecules of complex are simultaneously bound to the protein), and a good relaxivity that increases in the range 20-80 MHz. The relaxation enhancement is due to second sphere water molecules likely forming H-bonds with the coordinating phenoxide oxygens. A further enhancement was observed upon the formation of the supramolecular adduct with albumin. The binding sites of Fe(deferasirox)2 on albumin were characterized by relaxometric competitive assays. Preliminary in vivo imaging studies on a tumor-bearing mouse model indicate that, on a 3 T MRI scanner, the contrast ability of Fe(deferasirox)2 is comparable to the one shown by the commercial Gd(DTPA) agent. ICP-MS analyses on blood samples withdrawn from healthy mice administered with a dose of 0.1 mmol/kg of Fe(deferasirox)2 showed that the complex is completely removed in 24 h.

Hyperpolarized (13) C-labelled anhydrides as DNP precursors of metabolic MRI agents.

The extraordinary enhancement of the nuclear magnetic resonance (NMR) signal that can be obtained by dynamic nuclear polarization (DNP) techniques is prompting new avenues of research based on the in vivo detection of metabolic abnormalities associated with the onset and progression of human diseases. (13) C-labelled short-chain fatty acids appear to be interesting candidates for this novel class of metabolic-active contrast agents (MCAs), as they have been shown to report on metabolic differences between healthy and ischaemic tissues in mice. In spite of their promising biological efficacy, the formulations of short-chain fatty acids that fulfil the many technical constraints of the DNP procedure, as it is today, may limit their clinical potential. New solutions have been sought to circumvent technology-related challenges and facilitate clinical translation of these molecules. In particular, it has been shown that, by using symmetric anhydrides as chemical precursors for short-chain fatty acids, no glass-forming additives are needed in the DNP formulations. Furthermore, novel esterified trityl radicals and lipophilic gadolinium complexes allow easy removal of the polarization-promoting additives at the end of the DNP process. By applying the three concepts reported, we have succeeded in preparing aqueous formulations of short-chain fatty acids for pharmaceutical use that have favourable properties compared with those obtained from current procedures. The use of organic derivatives as chemical precursors of the MCA of interest appears to be a generally valid concept, not restricted to symmetric anhydrides of fatty acids, which can markedly improve the clinical potential of other (13) C-labelled compounds.

Novel functionalized pyridine-containing DTPA-like ligand. Synthesis, computational studies and characterization of the corresponding Gd(III) complex.

A novel pyridine-containing DTPA-like ligand, carrying additional hydroxymethyl groups on the pyridine side-arms, was synthesized in 5 steps. The corresponding Gd(III) complex, potentially useful as an MRI contrast agent, was prepared and characterized in detail by relaxometric methods and its structure modeled by computational methods.

[Gd-AAZTA]-: a new structural entry for an improved generation of MRI contrast agents.

An innovative MRI contrast agent based on the unprecedented and easily obtained ligand AAZTA is described. The simple and straightforward synthesis of the ligand, together with the potentiometric and relaxometric behavior of the corresponding Gd(III) chelate, is reported. The complex [Gd(AAZTA)]- shows outstanding magnetic properties connected with high thermodynamic stability in aqueous solution and a nearly complete inertness toward the influence of bidentate endogenous anions, placing this compound as one of the most promising candidates for the development of high performance MRI contrast agents.

Mannich reaction as a new route to pyridine-based polyaminocarboxylic ligands.

The Mannich reaction was successfully employed to obtain two pyridine-based ligands 1 and 2. The latter represents the first example of a Mannich reaction leading to a 12-membered pyridine-containing macrocycle. [reaction: see text]