Use of FCC-NMRD relaxometry for early detection and characterization of ex-vivo murine breast cancer

We acknowledge COST Action AC15209 (EURELAX) for scientific support. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 668119 (project “IDentIFY”). The Italian Ministry for Education and Research (MIUR) is gratefully aknowledged for yearly FOE funding to the Euro-BioImaging Multi-Modal Molecular Imaging Italian Node (MMMI). E.D.G. and G.F. gratefully acknowledge FIRC-AIRC (Fondazione Italiana per la Ricerca sul Cancro AIRC) for their fellowships. We gratefully acknowledge Lionel Broche for the interesting discussion about mathematical models and procedures for the fitting of NMRD data.Peer reviewedPublisher PD

Optimizing the relaxivity of MRI probes at high magnetic field strengths with binuclear GdIIIComplexes

The key criteria to optimize the relaxivity of a Gd(III) contrast agent at high fields (defined as the region 65 1.5 T) can be summarized as follows: (i) the occurrence of a rotational correlation time \u3c4R in the range of ca. 0.2\u20130.5 ns; (ii) the rate of water exchange is not critical, but a \u3c4M < 100 ns is preferred; (iii) a relevant contribution from water molecules in the second sphere of hydration. In addition, the use of macrocycle-based systems ensures the formation of thermodynamically and kinetically stable Gd(III) complexes. Binuclear Gd(III) complexes could potentially meet these requirements. Their efficiency depends primarily on the degree of flexibility of the linker connecting the two monomeric units, the absence of local motions and the presence of contribution from the second sphere water molecules. With the aim to maximize relaxivity (per Gd) over a wide range of magnetic field strengths, two binuclear Gd(III) chelates derived from the well-known macrocyclic systems DOTA-monopropionamide and HPDO3A (Gd2L1 and Gd2L2, respectively) were synthesized through a multistep synthesis. Chemical Exchange Saturation Transfer (CEST) experiments carried out on Eu2L2 at different pH showed the occurrence of a CEST effect at acidic pH that disappears at neutral pH, associated with the deprotonation of the hydroxyl groups. Then, a complete 1H and 17O NMR relaxometric study was carried out in order to evaluate the parameters that govern the relaxivity associated with these complexes. The relaxivities of Gd2L1 and Gd2L2 (20 MHz, 298 K) are 8.7 and 9.5 mM 121 s 121, respectively, +77% and +106% higher than the relaxivity values of the corresponding mononuclear GdDOTAMAP-En and GdHPDO3A complexes. A significant contribution of second sphere water molecules was accounted for the strong relaxivity enhancement of Gd2L2. MR phantom images of the dinuclear complexes compared to GdHPDO3A, recorded at 7 T, confirmed the superiority of Gd2L2. Finally, ab initio (DFT) calculations were performed to obtain information about the solution structure of the dinuclear complexes

Eight-Coordinate, Stable Fe(II) Complex as a Dual 19F and CEST Contrast Agent for Ratiometric pH Imaging

Accurate mapping of small changes in pH is essential to the diagnosis of diseases such as cancer. The difficulty in mapping pH accurately in vivo resides in the need for the probe to have a ratiometric response so as to be able to independently determine the concentration of the probe in the body independently from its response to pH. The complex FeII-DOTAm-F12 behaves as an MRI contrast agent with dual 19F and CEST modality. The magnitude of its CEST response is dependent both on the concentration of the complex and on the pH, with a significant increase in saturation transfer between pH 6.9 and 7.4, a pH range that is relevant to cancer diagnosis. The signal-to-noise ratio of the 19F signal of the probe, on the other hand, depends only on the concentration of the contrast agent and is independent of pH. As a result, the complex can ratiometrically map pH and accurately distinguish between pH 6.9 and 7.4. Moreover, the iron(II) complex is stable in air at room temperature and adopts a rare 8-coordinate g..

Generation of multiparametric MRI maps by using Gd-labelled-RBCs reveals phenotypes and stages of murine prostate cancer

We acknowledge BRACCO Imaging for providing Gadoteridol (ProHance). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 668119 (project “IDentIFY”) and No 667510 (project “GLINT”) and it was performed in the framework of COST Action AC15209 (EURELAX). E.D.G. and G.F. were supported by FIRC-AIRC (Fondazione Italiana per la Ricerca sul Cancro AIRC) fellowships.Peer reviewedPublisher PD