Robert N. Muller

Invited for the cover of this issue is the group of Sophie Laurent from the University of Mons, Belgium. The cover image shows a blood vessel containing the bimodal probe reported in this paper.

One of the most widely used techniques to obtain anatomical information is magnetic resonance imaging (MRI). Despite its high resolution, it has a low sensitivity which could be enhanced by coupling MRI with a more sensitive technique such as photoacoustic imaging (PAI). The development of a bimodal agent could thus lead to hybrid images with a high anatomical resolution provided by MRI and a precise localization of the contrast agent thanks to PAI. The probes used in this work are a gadolinium(III) complex derived from PCTA‐[12] for MRI and the ZW800–1 fluorophore for PAI. These two organic parts have been attached to a L‐lysine derivative which has a third site for potential conjugation to a biovector, thus opening the field of targeted probes for molecular imaging. Preliminary relaxometric and photoacoustic characterizations indicate that this bimodal agent is a promising compound for bimodal imaging.

The biodistribution of dendronized iron oxides, NPs10@D1_DOTAGA and melanin-targeting NPs10@D1_ICF_DOTAGA, was studied in vivo using MRI and planar scintigraphy through [177Lu]Lu-radiolabeling. MRI experiments showed high contrast power of both dendronized nanoparticles (DPs) and hepatobiliary and urinary excretions. Little tumor uptake could be highlighted after intravenous injection probably as a consequence of the negatively charged DOTAGA-derivatized shell which reduces the diffusion across the cells’ membrane. Planar scintigraphy images demonstrated a moderate specific tumor uptake of melanoma-targeted [177Lu]Lu-NPs10@D1_ICF_DOTAGA at 2 h post intravenous injection, and the highest tumor uptake of the control probe [177Lu]Lu-NPs10@D1_DOTAGA at 30min pi, probably due to the enhanced permeability and retention (EPR) effect. In addition, ex vivo Confocal microscopy (EVCM) studies showed a high specific targeting of human melanoma samples impregnated with NPs10@D1_ICF_Alexa647_ DOTAGA.

A new ditopic ligand (L) based on a 2,2′:5′,4″-terpyridine unit substituted in the 2″,6″ positions with iminodiacetate arms has been designed and synthesized for the construction of Ru^IIL₃Ln₃^III supramolecular architectures. The two components of this system, a 2,2′-bipyridine unit for Ru^II coordination and a pyridine-bis(iminodiacetate) core for Ln^III coordination, are tightly connected via a covalent C_arom(py)–C_arom(py) bond. The paramagnetic and photophysical properties of the corresponding tetrametallic Ru^IIL₃Gd₃^III complex have been evaluated, highlighting the potential of this metallostar structure to act as a bimodal MRI/optical imaging agent. Variable-temperature ¹⁷O NMR and proton nuclear magnetic relaxation dispersion (NMRD) measurements showed that this complex exhibits (i) a remarkable relaxivity per metallostar molecule, particularly at clinical and high magnetic fields (r₁^310K = 51.0 and 36.0 mM^–1 s^–1 at 20 and 300 MHz, respectively) and (ii) a near-optimal residence lifetime of Gd^III coordinated water molecule (τ_M^310K = 77.5 ns). This is the result of the presence of two inner-sphere water molecules in the Gd^III components of the metallostar and a slow tumbling rate of the molecule (τ_R^310K = 252 ps). Upon excitation in the visible domain (λ_exc = 472 nm), the Ru^II component of the complex exhibits a bright-red luminescence centered at 660 nm with a quantum yield of 2.6% in aqueous solutions at pH 7.4. Moreover, this Ru^IIL₃Gd₃^III assembly is also characterized by a high kinetic inertness in biological media (PBS and human serum solutions) and a high photostability (photobleaching). Finally, preliminary photophysical studies on RuL₃Nd₃ and RuL₃Yb₃ assemblies revealed that the Ru^II center acts as an effective sensitizer for Ln^III-based luminescence in the near-IR region. The Nd^III species was found to be the most effective at quenching the ³MLCT luminescence of the Ru center.

Magnetic resonance imaging (MRI) offers the possibility of tracking cells labelled with a contrast agent and evaluating the progress of cell therapies. This requires efficient cell labelling with contrast agents. A basic incubation of cells with iron oxide nanoparticles (NPs) is a common method. This study reports the synthesis at the gram scale of iron oxide nanoparticles as MRI T₂ contrast agents for cell labelling. These NPs are based on small iron oxide cores coated with a thin polysiloxane shell presenting carboxylic acid functions. The iron oxide cores produced have been characterized by transmission electron microscopy, X-ray diffraction, ζ-potential, infrared, photon correlation spectroscopy, atomic force microscopy, magnetometry and relaxometric measurements. These measurements confirmed the expected surface modification by carboxysilane. Carboxylic groups created electrostatic repulsion between NPs when they are deprotonated. Therefore, highly concentrated aqueous solutions of carboxysilane coated iron oxide NPs can be obtained, up to 70% (w/w). These NPs could be used for cell labelling owing to their aggregation and re-dispersion properties. NPs precipitated in Dulbecco's modified Eagle medium induced a rapid association with 3 T6 fibroblast cells and could easily be re-dispersed in phosphate buffer saline solution to obtain properly labelled cells.

Six diethylene triamine pentaacetic acid (DTPA) bisamide derivatives functionalized with p‐toluidine (DTPA‐BTolA), 6‐aminocoumarin (DTPA‐BCoumA), 1‐naphthalene methylamine (DTPA‐BNaphA), 4‐ethynylaniline (DTPA‐BEthA), p‐dodecylaniline (DTPA‐BC₁₂PheA) and p‐tetradecyl‐aniline (DTPA‐BC₁₄PheA) were coordinated to dysprosium(III) and the magnetic and optical properties of the complexes were examined in detail. The complexes consisting of amphiphilic ligands (DTPA‐BC₁₂PheA and DTPA‐BC₁₄PheA) were further assembled into mixed micelles. Upon excitation into the ligand levels, the complexes display characteristic Dy^III emission with quantum yields of 0.3–0.5 % despite the presence of one water molecule in the first coordination sphere. A deeper insight into the energy‐transfer processes has been obtained by studying the photophysical properties of the corresponding Gd^III complexes. Since the luminescence quenching effect is decreased by the intervention of non‐ionic surfactant, quantum yields up to 1 % are obtained for the micelles. The transverse relaxivity r₂ per Dy^III ion at 500 MHz and 310 K reaches a maximum value of 27.4 s⁻¹ mM⁻¹ for Dy‐DTPA‐BEthA and 36.0 s⁻¹ mM⁻¹ for the Dy‐DTPA‐BC₁₂PheA assemblies compared with a value of 0.8 s⁻¹ mM⁻¹ for Dy‐DTPA. The efficient T₂ relaxation, especially at high magnetic field strengths, is sustained by the high magnetic moment of the dysprosium ion, the coordination of water molecules with slow water exchange kinetics and long rotational correlation times. These findings open the way to the further development of bimodal optical and magnetic resonance imaging probes starting from single lanthanide compounds.