Clavijo Jordan M Veronica, Beeman Scott C, Baldelomar Edwin J, Bennett Kevin M
School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona, USA.
Contrast Media Mol Imaging. 2014 Sep-Oct;9(5):323-32. doi: 10.1002/cmmi.1578. Epub 2014 Apr 25.
Inorganic doping was used to create flexible, paramagnetic nanoparticle contrast agents for in vivo molecular magnetic resonance imaging (MRI) with low transverse relaxivity (r2). Most nanoparticle contrast agents formed from superparamagnetic metal oxides are developed with high r2. While sensitive, they can have limited in vivo detection due to a number of constraints with T2 or T2*-weighted imaging. T1-weighted imaging is often preferred for molecular MRI, but most T1-shortening agents are small chelates with low metal payload or are nanoparticles that also shorten T2 and limit the range of concentrations detectable with T1-weighting. Here we used tungsten and iron deposition to form doped iron oxide crystals inside the apoferritin cavity to form a WFe nanoparticle with a disordered crystal and un-coupled atomic magnetic moments. The atomic magnetic moments were thus localized, resulting in a principally paramagnetic nanoparticle. The WFe nanoparticles had no coercivity or saturation magnetization at 5 K and sweeping up to ± 20,000 Oe, while native ferritin had a coercivity of 3000 Oe and saturation at ± 20,000 Oe. This tungsten-iron crystal paramagnetism resulted in an increased WFe particle longitudinal relaxivity (r1) of 4870 mm(-1) s(-1) and a reduced transverse relaxivity (r2) of 9076 mm(-1) s(-1) compared with native ferritin. The accumulation of the particles was detected with T1-weighted MRI in concentrations from 20 to 400 nm in vivo, both injected in the rat brain and targeted to the rat kidney glomerulus. The WFe apoferritin nanoparticles were not cytotoxic up to 700 nm particle concentrations, making them potentially important for targeted molecular MRI.
无机掺杂被用于制造灵活的顺磁性纳米颗粒造影剂，用于体内分子磁共振成像（MRI），其横向弛豫率（r2）较低。大多数由超顺磁性金属氧化物形成的纳米颗粒造影剂具有较高的r2。虽然灵敏，但由于T2或T2*加权成像存在一些限制，它们在体内的检测可能会受到限制。分子MRI通常更倾向于使用T1加权成像，但大多数T1缩短剂是金属负载量低的小螯合物，或者是也会缩短T2并限制T1加权可检测浓度范围的纳米颗粒。在这里，我们利用钨和铁沉积在脱铁铁蛋白腔内形成掺杂的氧化铁晶体，以形成具有无序晶体和未耦合原子磁矩的WFe纳米颗粒。原子磁矩因此被定位，从而形成主要为顺磁性的纳米颗粒。WFe纳米颗粒在5 K且扫描至±20,000 Oe时没有矫顽力或饱和磁化强度，而天然铁蛋白在±20,000 Oe时具有3000 Oe的矫顽力和饱和磁化强度。这种钨 - 铁晶体顺磁性导致WFe颗粒的纵向弛豫率（r1）增加至4870 mm(-1) s(-1)，横向弛豫率（r2）降低至9076 mm(-1) s(-1)，与天然铁蛋白相比。通过T1加权MRI在体内检测到浓度为20至400 nm的颗粒积累，这些颗粒既被注射到大鼠脑中，也被靶向到大鼠肾脏肾小球。WFe脱铁铁蛋白纳米颗粒在高达700 nm的颗粒浓度下没有细胞毒性，这使得它们在靶向分子MRI中具有潜在的重要性。
