Organically coated iron oxide crystallites with diameters of 5-50 nm ("nanoparticles") are potential magnetic resonance imaging contrast agents. 1/T1 and 1/T2 of solvent water protons are increased dramatically by magnetic interactions in the "outer sphere" environment of the nanoparticles; subsequent diffusive mixing distributes this relaxation throughout the solvent. Published theory, valid for the solute magnetic energy small compared with thermal energy, is applicable to small magnetic solutes (e.g., gadolinium and manganese diethylenetriaminopentaacetic acid, and nitroxide free radicals) at generally accessible fields (< or = 50 T). It fails for nanoparticles at fields above approximately 0.05 T, i.e., at most imaging fields. The authors have reformulated outer sphere relaxation theory to incorporate progressive magnetic saturation of solute nanoparticles and, in addition, indicate how to use empirical magnetization data for realistic particles when their magnetic properties are not ideal. It is important to handle the effects of rapid thermally induced reorientation of the magnetization of the nanoparticles (their "superparamagnetism") effectively, including their sensitivity to particle size. The theoretical results are presented as the magnetic field dependence (NMRD profiles) of 1/T1 and 1/T2, normalized to Fe content, for three sizes of particles, and then compared with the limited data extant for well-characterized material.

A variable-temperature, multiple-field 17 O NMR and EPR spectroscopic study has been performed on three Gd(DTPA-bisamide)alkyl copolymers, [Gd(DTPAÀBA)À(CH 2 ) n ] x (n 6, 10,12;N,N',N'',. The rate and mechanism of water exchange is identical for the polymer complexes and [Gd(DTPAÀBMA)(H 2 O)], which can be considered as the monomer unit of the polymers. Transverse electronic relaxation rates, measured by EPR, increase with increasing rotational correlation time. Rigid intramolecular micellelike structures form in aqueous solutions of the Gd(DTPA-bis-amide)alkyl copolymers. Consequently, the longitudinal 17 O relaxation rates for [Gd(DTPA À BA) À (CH 2 ) 10 ] x and [Gd(DTPA À BA) À (CH 2 ) 12 ] x , were interpreted with the Lipari ± Szabo treatment. This involves the inclusion of a global correlation time, representing the motion of the whole micellelike association, and a local correlation time, representing the motion of the GdÀO vector. The global correlation time ob-tained for the two polymers reflects the ratio of the molecular weights, whereas the local correlation times and the general order parameters are similar for both copolymers. The proton relaxivity difference can be explained by the different global correlation times. Thus, contrary to linear polymers in general, for the present polymers the global motion significantly contributes to relaxivity. Relaxivity is limited by water exchange; simulations show that proton relaxivities over 100 mm À1 s À1 could be obtained by substituting the Gd(DTPAbisamide) units with a gadolinium chelate with fast water exchange.

Macromolecular contrast media offer potential advantages over freely diffusible agents in magnetic resonance (MR) imaging outside the central nervous system. To identify an optimum molecular weight for macromolecular contrast media, the authors studied a novel macromolecular contrast agent, gadolinium diethylenetriaminepentaacetic acid polyethylene glycol (DTPA-PEG), synthesized in seven polymer (average) molecular weights ranging from 10 to 83 kd. Twenty-eight rabbits bearing V2 carcinoma in thighs underwent T1-weighted spin-echo imaging before injection and 5-60 minutes and 24 hours after injection of the Gd-DTPA-PEG polymers or Gd-DTPA at a gadolinium dose of 0.1 mmol/kg. Tumor region-of-interest measurements were obtained at each time point to determine contrast enhancement dynamics. Blood-pool enhancement dynamics were observed for the Gd-DTPA-PEG polymers larger than 20 kd. Polymers smaller than 20 kd displayed dynamics similar to those of the freely diffusible agent Gd-DTPA. Above the 20 kd threshold, tumor enhancement was more rapid for smaller polymers. The authors conclude that the 21.9-kd Gd-DTPA-PEG polymer is best suited for clinical MR imaging.

We have synthesized and evaluated five series of polymeric gadolinium chelates which are of interest as potential MRI blood pool contrast agents. The polymers were designed so that important physical properties including molecular weight, relaxivity, metal content, viscosity, and chelate stability could be varied. We have shown that, by selecting polymers of the appropriate MW, extended blood pool retention can be achieved. In addition, relaxivity can be manipulated by changing the polymer rigidity, metal content affected by monomer selection, viscosity by polymer shape, and chelate stability by chelator selection.

A preparation of monocrystalline iron oxide nanoparticles with an oxidized starch coating, currently in clinical trials (NC100150 Injection; CLARISCAN™), was characterized by magnetization measurements, relaxometry, and photon correlation spectroscopy. By combining the results with a measure of iron content, one can obtain the size and magnetic attributes of the iron cores, including the relevant correlation times for outer sphere relaxation (SO and D), and information about the interaction of the organic coating with both core and solvent. The results are 6.43 nm for the iron oxide core diameter, a magnetic moment of 4.38 10 17 erg/G, and a water-penetrable coating region of oxidized oligomeric starch fragments and entrained water molecules. The latter extends the hydrodynamic diameter to 11.9 nm and lowers the average diffusivity of solvent about 64% (which increases D accordingly). The nanopar-ticles show little size-polydispersity, evidenced by the lowest value of r 2 /r 1 at 20 MHz reported to date, an asset for magnetic resonance angiography. J. Magn. Reson. Imaging 2000;11:488-494.

A series of linear copolymers of DTPA-class Gd3+ conjugates, linked by alpha, omega-alkyldiamides with a varying number (n) of methylenes separating the amide function, were synthesized. Surprisingly, their relaxivities at all fields increased with increasing n. At MRI fields and 35 degrees C, the relaxivities of the n = 10 and n = 12 polymers were unexpectedly high, similar to those of rigid dendrimer-based Gd3+ chelates. The magnetic field dependence of solvent proton 1/T1 was measured for aqueous urea-free and urea-containing polymer solutions. The results for urea-free solutions imply an increase of rigidity (required for high relaxivities) with increasing n, arising from hydrophobic interactions of the methylene groups with solvent. This hypothesis is supported by a large decrease in the relaxivities upon addition of urea, which is known to weaken hydrophobic interactions. The relaxivities are also independent of polymer concentration, indicating that the hydrophobic interactions are intramolecular.

No abstract

No abstract