Magnetic Resonance Imaging (MRI) is an attractive platform for medical imaging because it uses neither harmful radiation nor expensive radio-tracers;however, MRI, even with the aid of suitable contrast agents, is plagued by background noise from the host tissue and lacks the ability to quantify exactly how much contrast agent is present at a given location. Despite the fact that contrast agents are useful in imaging and differentiating abnormal tissues (tumors) from healthy tissues at much larger scales, early detection of a few-thousand cancer cells is difficult due to the lack of contrast differentiating the tumor from surrounding healthy tissue. Additionally, quantification of cells at the disease site is crucial for development of more site-specific contrast agents that will enable future developments in image-guided therapeutics. Thus, there is a critical need to develop magnetic molecular probes that, unlike contrast agents, can be directly imaged, irrespective of the surrounding tissue, and can be simultaneously targeted to disease sites for early diagnostic imaging. Our goal is to use Magnetic Particle Imaging (MPI), a new medical imaging technology recently introduced by Philips that uses the magnetic relaxation of magnetite nanoparticles in alternating fields, to produce three-dimensional images of the distribution of the nanoparticles in the tissue. The magnetic nanoparticles will have a million times more signal in MPI compared to the nuclear paramagnetism of protons used in MRI. Royal Philips and Bruker Biospin, have jointly announced the development of a preclinical MPI hardware and imaging system, to be marketed in 2011/12. However, commercially available magnetite formulations are grossly inadequate for MPI, both in terms of signal intensity and spatial resolution. In fact, if this critical component, i.e. appropriate magnetite nanoparticle-based molecular probes, that are biocompatible and surface functionalized for facile bioconjugation, and tailored for optimal, performance, are not developed now the enormous potential of MPI may never be realized. Based on our knowhow, we propose to develop the technology of the molecular probes crucially required for the success of MPI in a most timely manner. Our three specific aims (SA) will focus on (SA1) development of monodispersed and biocompatible magnetic nanoparticles (MNPs) as molecular probes optimized for any specific driving frequency used in MPI, (SA2) functionalize the MNPs for specific targeting to tumor cells and the surrounding vasculature and determine the targeting effectiveness in vitro, and (SA3) demonstrate MPI's ability to detect and quantify our targeted MNPs in vitro using a home-built magnetic spectrometer, thereby setting the stage for Phase II work involving in vivo imaging and quantification.

Public Health Relevance

Medical imaging, in its many forms, is a crucial technique used by clinicians for diagnosing diseases and determining the correct treatment options for patients. Diagnosis of cancer, a disease that has resulted in over 550,000 deaths in the United States in 2010 alone (National Cancer Institute;www.cancer.gov), is especially difficult and often detected at much later stages when patient survival chances are low. For early detection of a few-thousand cells, it is important to use nanometer-scale probes (1 nanometer = 1 billionth of a meter) that can specifically target cancer cells and be directly imaged, without any interference or noise from the patient's body. In this project, we will develop functionalized magnetic nanoparticle-based molecular probes, with a million times more signal than nuclear paramagnetism used in MRI, for early detection of cancer using a new and emerging technique called Magnetic Particle Imaging (MPI). Our technology will complement the hardware being developed by Philips, the inventors of MPI. This technology, if successful, will be superior to current imaging techniques such as Magnetic Resonance Imaging (MRI) and has the potential to enable early diagnosis, giving patients a head start in the fight against cancer.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Small Business Technology Transfer (STTR) Grants - Phase I (R41)
Project #
1R41EB013520-01
Application #
8123812
Study Section
Special Emphasis Panel (ZRG1-SBMI-T (10))
Program Officer
Liu, Christina
Project Start
2011-08-04
Project End
2013-07-31
Budget Start
2011-08-04
Budget End
2013-07-31
Support Year
1
Fiscal Year
2011
Total Cost
$220,316
Indirect Cost
Name
Lodespin Labs, LLC
Department
Type
DUNS #
962761842
City
Seattle
State
WA
Country
United States
Zip Code
98103
Yu, Elaine Y; Bishop, Mindy; Zheng, Bo et al. (2017) Magnetic Particle Imaging: A Novel in Vivo Imaging Platform for Cancer Detection. Nano Lett 17:1648-1654
Yu, Elaine Y; Chandrasekharan, Prashant; Berzon, Ran et al. (2017) Magnetic Particle Imaging for Highly Sensitive, Quantitative, and Safe in Vivo Gut Bleed Detection in a Murine Model. ACS Nano 11:12067-12076
Bao, Yuping; Wen, Tianlong; Samia, Anna Cristina S et al. (2016) Magnetic Nanoparticles: Material Engineering and Emerging Applications in Lithography and Biomedicine. J Mater Sci 51:513-553
Croft, Laura R; Goodwill, Patrick W; Konkle, Justin J et al. (2016) Low drive field amplitude for improved image resolution in magnetic particle imaging. Med Phys 43:424
Kemp, Scott J; Ferguson, R Matthew; Khandhar, Amit P et al. (2015) Gram scale synthesis of magnetite nanoparticles optimized for single-core MPI tracers. Int Workshop Magn Part Imaging 2015:
Arami, Hamed; Khandhar, Amit; Liggitt, Denny et al. (2015) In vivo delivery, pharmacokinetics, biodistribution and toxicity of iron oxide nanoparticles. Chem Soc Rev 44:8576-607
Khandhar, Amit P; Kemp, Scott J; Ferguson, R Matthew et al. (2015) Tunable in vivo circulation characteristics of PEGylated MPI tracers. Int Workshop Magn Part Imaging 2015:
Ferguson, R Matthew; Khandhar, Amit P; Kemp, Scott J et al. (2015) Magnetic particle imaging with tailored iron oxide nanoparticle tracers. IEEE Trans Med Imaging 34:1077-84
Khandhar, Amit P; Ferguson, R Matthew; Arami, Hamed et al. (2015) Tuning surface coatings of optimized magnetite nanoparticle tracers for in vivo Magnetic Particle Imaging. IEEE Trans Magn 51:
Arami, Hamed; Khandhar, Amit P; Tomitaka, Asahi et al. (2015) In vivo multimodal magnetic particle imaging (MPI) with tailored magneto/optical contrast agents. Biomaterials 52:251-61

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