Monodispersed magnetic nanoparticles for improved diagnostic imaging. Phase II: S

描述（由申请人提供）：在拟议的II期NIH STTR资助机会（PA-12-089）中，LodeSpin Labs（LSL）正在开发一种用于磁性粒子成像（MPI）的磁性纳米粒子示踪剂，这是一种颠覆性的新医学成像技术，目前正在开发作为现有心脏成像技术（如CT和MRI）的安全，有效和定量替代品。MPI是当前CT血管造影程序的一种有前途的更安全的替代方案;它使用安全的磁场（无电离辐射）和安全的氧化铁纳米颗粒示踪剂。与MRI不同，它提供定量的实时成像，并具有亚毫米空间分辨率的潜力。MPI显示出巨大的潜力，作为一种安全的临床成像程序，用于诊断和治疗心血管疾病（美国的头号死亡原因），并打开了新的分子成像应用的大门。然而，它仍然在开发中，主要是由于没有合适的示踪剂。虽然存在氧化铁纳米颗粒示踪剂，但已开发用于MRI以及CKD患者的铁替代（Feraheme），LSL的示踪剂是第一个也是唯一一个专门为MPI设计的示踪剂。此外，在开发MPI硬件的工业和学术研究团体中，LSL示踪剂提供了上级MPI成像性能，这将实现MPI的临床和商业潜力，这是一致同意的。因此，LSL有很大的机会成为新兴的临床前MPI市场和未来临床市场的第一家高性能MPI示踪剂供应商。在第二阶段，UW和LSL与工业巨头Bruker BioSpin和Philips Medical Systems合作，将在幻影和活体动物中展示实时体内成像。LSL进一步加强了其团队，包括作为成像科学家顾问的Steven Conolly博士和作为共轭和药物化学顾问的Julian Simon博士。LSL还将进行毒理学试验研究，向未来的投资者证明示踪剂的安全性，并使合资企业能够最终为未来的监管研究提供资金。在第一阶段，我们努力开发优化的示踪剂，并与飞利浦医疗系统（有限评估许可证）和加州大学伯克利分校的Conolly博士团队（材料转让协议）建立了战略合作伙伴关系，使LSL团队成为MPI示踪剂技术的先驱。MPI社区一致认为LSL示踪剂优于目前市场上的任何氧化铁制剂。因此，我们设想我们的示踪剂能够真正使MPI实现其临床和商业潜力。在第二阶段，LSL的直接目标是证明我们的示踪剂在体模和体内成像中的上级性能，在时域和频域图像重建方法中的亚毫米分辨率（SA 1），进一步增强示踪剂性能，以与X射线CA程序中的当前标准竞争（SA 2），并在小鼠中的初步毒理学研究中评估示踪剂安全性（SA 3）。

DESCRIPTION (provided by applicant): In the proposed phase II NIH STTR funding opportunity (PA-12-089), LodeSpin Labs (LSL) is developing a magnetic nanoparticle tracer for use in Magnetic Particle Imaging (MPI), a disruptive new medical imaging technology currently being developed as a safe, effective and quantitative alternative to existing cardiac imaging technologies like CT and MRI. MPI is a promising safer alternative to current CT angiography procedures; it uses safe magnetic fields (no ionizing radiation) and safe iron oxide nanoparticle tracers. Unlike MRI, it offers real-time imaging that is quantitative and has potential for sub-mm spatial resolution. MPI shows tremendous potential as a safe clinical imaging procedure for diagnosis and treatment of cardiovascular disease (#1 cause of deaths in the US), and opens doors to novel molecular imaging applications. However, it remains under development largely due to the unavailability of suitable tracers. While iron oxide nanoparticle tracers exist, having been developed for MRI as well as for iron replacement in CKD patients (Feraheme), LSL's tracer is the first, and only, tracer to be designed specifically for MPI. Furthermore, there is unanimous agreement in the industrial and academic research community developing MPI hardware that LSL tracers provide superior MPI imaging performance, which will enable MPI's clinical and commercial potential. Therefore, LSL has a significant opportunity to be the first provider of high-performing MPI tracers in the emerging pre-clinical MPI market and future clinical market. In Phase II, UW and LSL, in partnership with industrial giants Bruker BioSpin and Philips Medical Systems, will demonstrate real-time in vivo imaging in phantoms and live animals. LSL has further strengthened its team by including Dr. Steven Conolly, as an imaging scientist consultant, and Dr. Julian Simon, as a conjugation and medicinal chemistry consultant. LSL will also pursue pilot toxicology studies that will demonstrate tracer safety to future investors and enable joint ventures that will ultimately fund future regulatory studies. In Phase I our efforts to develop optimized tracers, and strategic partnerships with Philips Medical Systems (Limited Evaluation License) and Dr. Conolly's group at UC-Berkley (Material Transfer Agreement) have positioned the LSL team as pioneers in MPI tracer technology. There is unanimous agreement in the MPI community that LSL tracers outperform any iron oxide formulation currently in the market. Thus, we envision our tracers as truly enabling MPI in achieving its clinical and commercial potential. In Phase II, LSL's immediate goals are to demonstrate our tracer's superior performance in phantom and in vivo imaging, targeting sub-mm resolution (SA1) in both time- and frequency-domain image reconstruction methods, further enhance tracer performance to compete with current standards in x-ray CA procedures (SA2), and assess tracer safety in pilot toxicology studies in mice (SA3).