NMR Transversal Relaxivity of Suspensions of Lanthanide Oxide Nanoparticles Malgorzata Norek, † Giovannia A. Pereira, ‡ Carlos F. G. C. Geraldes, ‡ Antonia Denkova, § Wuzong Zhou, # and Joop A. Peters* ,† Biocatalysis and Organic Chemistry, Department of Biotechnology, Delft UniVersity of Technology, Julianalaan 136, 2628 BL Delft, The Netherlands, NMR Center and Center of Neuroscience and Cell Biology, Department of Biochemistry, UniVersity of Coimbra, P. O. Box 3126, 3001-401 Coimbra, Portugal, Physical Chemistry and Molecular Thermodynamics, Delft UniVersity of Technology, 2628 BL Delft, The Netherlands, and School of Chemistry, UniVersity of St. Andrews, Fife KY16 9ST, United Kingdom ReceiVed: March 22, 2007; In Final Form: May 11, 2007 Aqueous suspensions of paramagnetic lanthanide oxide nanoparticles have been studied by NMR relaxometry. The observed R 2 * relaxivities are explained by the static dephasing regime (SDR) theory. The corresponding R 2 relaxivities are considerably smaller and are strongly dependent on the interval between the two refocusing pulses. The experimental data are rationalized by assuming the value of the diffusion correlation time, τ D , to be very long in a layer with adsorbed xanthan on the particle’s surface. In this layer, the refocusing pulses are fully effective and R 2 ≈ 0. Outside this layer, the diffusion model for weakly magnetized particles was applied. From the fit of the experimental relaxation data with this model, both the particle radii (r p ) and the radii of the spheres, within which the refocusing pulses are fully effective (r diff ), were estimated. The values of r p obtained are in agreement with those determined by dynamic light scattering. Because the value of r diff depends on the external magnetic field B and on the magnetic moment of the lanthanide of interest (μ eff 2 ), the R 2 relaxivity was found to be proportional to B and to μ eff 2 . 1. Introduction During the last decades, the rapid progress in biochemical research has provided detailed insight into molecular recognition processes. These developments enable the design of contrast agents (CAs) for molecular imaging 1 with medical diagnostic techniques including positron emission tomography (PET), single photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI). MRI has a significantly higher spatial resolution (μm) than radiodiagnostic techniques (mm), but its use as a tool for the investigation of cellular molecular events in normal and pathological processes is hampered by its low sensitivity: a relatively large local concentration of CA is required (about 10 -5 M) to achieve the desired contrast enhancement. 2,3 Other imaging modalities such as PET, SPECT (10 -11 -10 -12 M), and optical fluorescence imaging (10 -15 -10 -17 M) are much more adequate in this respect. 4 A possible approach to overcome the problems related with the low sensitivity of MRI is to apply vectorized CAs, which would bring a high payload of paramagnetic compound to the site of interest. For lanthanide ion based contrast agents, this was realized in various ways and different materials have been proposed including: Gd-loaded apoferritin, which allows the visualization of hepatocytes when the number of Gd-complexes per cell is about 4 × 10 7 , 5 perfluorocarbon nanoparticles, which contain around 94 200 Gd 3+ ions per particle providing ex- tremely high relaxivity per particle and which have been already successfully used in molecular imaging of angiogenesis. 6-10 Alternatively, this may be achieved with superparamagnetic (SPM) particles, single domain ferromagnets possessing a very high magnetic moment (around 10 4 μ B ). 11,12 SPM particles have a much smaller effect on the T 1 water proton relaxation time than on the T 2 . Their relaxivity can be well described by the quantum mechanical outer-sphere theory. Because of their small size (20-60 nm in diameter), the extreme motional narrowing conditions are satisfied, which state that water diffusion between SPM particles is rapid with respect to the difference in resonance frequencies of the various sites. In this regime the T 2 * relax- ation time is predicted to be equal to T 2 . When iron-oxide particles are compartmentalized within cells, the internal magnetization of the compartment due to their presence has to be taken into account. In this situation the motional narrowing assumption breaks down, which results in R 2 * () 1/T* 2 ) to be larger than R 2 . Consequently, R 2 * -weighted MRI images are potentially the most sensitive to the presence of cellularly compartmentalized magnetized particles. 13-15 Nanozeolites present another approach. Gd 3+ exchanged zeolite NaY nanoparticles of an average size of 80 nm, contain about 40 000 Gd 3+ ions per particle. The longitudinal relaxivity r 1 (r 1 is the relaxation rate expressed in s -1 mM -1 Gd) is limited by the water exchange between the interior of zeolites and the bulk. 16 It was observed that r 2 relaxivity is independent of the pore structure of the zeolite and that it increases with the external field strength. 17 In materials like Ln-AV-9, which have Ln 3+ ions incorporated in the zeolite framework, direct interaction between Ln 3+ ions and water molecules is impossible. As a result, they have a very low r 1 relaxivity, but at the same time they have a very strong impact on the T 2 relaxation. 18 * To whom correspondence should be addressed. E-mail: J.A.Peters@ tudelft.nl. † Biocatalysis and Organic Chemistry, Delft University of Technology. ‡ University of Coimbra. § Physical Chemistry and Molecular Thermodynamics, Delft University of Technology. # University of St. Andrews. 10240 J. Phys. Chem. C 2007, 111, 10240-10246 10.1021/jp072288l CCC: $37.00 © 2007 American Chemical Society Published on Web 06/23/2007